Fires constitute a significant threat due to the pollutants emitted and the destruction they cause. People who take part in fire-fighting operations must be equipped with appropriate tools, including special clothing that will allow them to work and guarantee safety. One of the threats are compounds from the PAH group, which are characterized by high toxicity and carcinogenicity. Therefore, it is important that the materials used constitute a barrier to contamination. Various materials from which individual elements of special firefighter's clothing are made were tested. Additionally, the importance of height on the possibility of sorption of PAH compounds on a given type of material was analyzed. Based on the results obtained, it was found that the type of material and the zone in which the clothing items are used are important in the sorption processes of pollutants. Data in this area may be important for taking further actions regarding the modification of materials used in special fire brigade clothing and in their cleaning processes.

In the process of oil and gas development and production, when the flow rate in the wellbore is large, the materials underground will be eroded, causing the operation to be unable to proceed smoothly and reducing the efficiency of oil and gas production. Therefore, optimizing the anti-erosion coating under high-speed flow conditions in wellbore is a very interesting thing. It can greatly improve operational efficiency. In this paper, laser cladding was used to prepare the new coating used in the PDC drill bit. Then, the effects of tungsten carbide and multi-layer graphene on the microstructure and properties of the tungsten carbide coating were studied. The research results indicate that, for new coatings, 60% tungsten carbide and 0.3% graphene are the optimal ratios. After adding WC, the hardness has significantly improved. However, when the WC content further increases more than 30%, the increase in hardness is relatively small. In addition, when the content of graphene is more than 0.3%, the branched structure became thicker, and not only the segregation of Cr, Si and W became very obvious again, but also the segregation of Fe occurred at the Ni enrichment site. The research results contribute to improving oil and gas production and operational efficiency under high-speed fluid flow conditions in the wellbore.

Methicillin-resistant Staphylococcus aureus (MRSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhancing the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with minimal inhibitory concentrations (MIC) ranging from 0.009-0.013 μg/mL and MBIC50 values ranging from 0.008-0.012 μg/mL, in planktonic and biofilm bacteria, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb/c mice were treated with RFB formulations and VCM at 20 and 40 mg/kg of body weight, respectively. Obtained data proved the superior therapeutic effectiveness of RFB formulations compared to Control and VCM groups even using a two-fold lower therapeutic dose as demonstrated by significantly reduced bacterial burden and growth index values in major organs. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.

Public restrooms are often a hub of microbial contamination, and the examination of bacterial contamination in these facilities can serve as an important indicator of the transmission of infectious diseases. This study was conducted to determine the prevalence of bacterial contamination in public restrooms based on the economic class of the building. Samples were collected from various spots in 32 restrooms found in 10 shopping malls, classifying them into two categories: upper-end restrooms and lower-end restrooms. The findings showed that the level of contamination was higher in the lower-end restrooms, with the seat being the most contaminated area. The most dominant Gram-positive bacteria were coagulase-negative staphylococci species, making up 86% of the identified Gram-positive isolates. The most dominant Gram-negative bacteria identified were Klebsiella pneumoniae and Pseudomonas aeruginosa. The antibiotic sensitivity test results revealed the presence of multi-drug resistant bacteria among the Gram-positive and negative isolates, including Staphylococcus haemolyticus, Staphylococcus kloosi, Acinetobacter baumanii, and Pseudomonas aeruginosa. In conclusion, the study underscores the significance of monitoring bacterial contamination in public restrooms and the need for measures to reduce the spread of infectious diseases. Further research is crucial to gain a complete understanding of the bacterial contamination in public restrooms and their resistance patterns, to ensure the safety and health of the public. The implementation of improved cleaning practices and hands-free designs in restrooms can help reduce the risk of cross-contamination and prevent the spread of diseases.

Correlations among estrus cycle, pyometra, and canine diabetes mellitus (CDM) have been described since the late 1950s, and substantial progress in understanding mechanisms beyond was achieved nowadays. Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. Thus, a deep understanding of the physiopathological aspects involved is crucial to postulate treatment guidelines to improve the PRDM remission rate, as well as to inform preventive measures. This narrative review aims to provide relevant detailed information on 1) canine estrus cycle and its impact on CDM etiology and management, 2) the role of pyometra as a further cause of insulin resistance, and 3) useful individual therapeutic and preventive strategies. Pharmacological annulment of progesterone effects, as well as inflammatory and progesterone-related conditions resolution in association with adequate exogenous insulin therapy, and residual beta cell function, are key aspects to achieve remission, or at least to improve diabetic clinical control. In this way, spaying should be considered mandatory in most PRDM cases. Preventive measures against CDM can include spaying recommendations; however, individual-based recommendations should be considered since castration may be associated with some long-term health issues.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

Nearly one third of men will incur biochemical recurrence after treatment for localized prostate cancer. Androgen deprivation therapy (ADT) is the therapeutic mainstay, however almost all patients will eventually transition to a castrate resistant state (castrate resistant prostate cancer, CRPC). Subjects with CRPC generally develop symptomatic metastatic disease (mCRPC) and incur mortality several years later. Prior to metastatic disease, men acquire non-metastatic CRPC (nmCRPC) which lends the unique opportunity for intervention to delay disease progression and symptoms. This review addresses current therapies for nmCRPC, as well as novel therapeutics and pathway strategies targeting men with nmCRPC.

Acute and chronic graft versus host disease (a/cGVHD) are major complications of allogeneic stem cell transplantation and a frequent cause of non relapse-mortality. The treatment of a/cGVHD consists of steroid administration at full dose. In the case of aGVHD, around 60 % of patients with grade III/IV fails to respond (steroid-resistant, SR), requiring a second line therapy. Extracorporeal photopheresis (ECP) represents a good option for second line treatment, leading to multiorgan response in several patients. Here, we have evaluated the performances of a cytofluorimetric quality control of the first ECP procedure in 29 patients with severe SR aGVHD who underwent ECP. The quality control represents a check control of in vitro cell apoptosis/death induction in collected and irradiated CD3+ cells by ECP. Our analysis shows that in more than 70 % quality controls a relevant apoptotosis/death of CD3+ cells was observed after cell irradiation, as compared to non-irradiated controls. Albeit observed in a small patients’ series, the occurrence of relevant in vitro effect after ECP relates to less procedures and/or to a better survival on ECP. Age, disease, gender, aGVHD grade and time from transplant to the first ECP had not impact on ECP efficacy in this patients’ series.

Enterococcus faecalis is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04 (ФKEN04), isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR Enterococcus faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between -80ᵒC and 37ᵒC. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G+C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that ФKEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.

Shigella and Salmonella have been implicated in neonatal sepsis, food poisoning, and bacteremia. Their increasing resistance to antibiotics has undermined treatment options, constituting a public health crisis. Also, the scarcity of new antibiotics in the development pipeline compounds multidrug-resistance (MDR). Hence, there is a need to potentiate antibiotics to mitigate resistance. This study leveraged riboflavin to re-sensitize fluoroquinolones and carbapenems against MDR Shigella and Salmonella spp. Disk diffusion, microbroth-dilution, chequerboard, and time-kill assays were used to determine resistance profiles and riboflavin-antibiotic activity. Biofilm-formation and bacterial viability (after riboflavin-antibiotic challenge) was determined with crystal-violet and Macrophage infection assays, respectively. Strains exhibited >80% resistance to fluoroquinolones and carbapenems, with 160–320 µg MIC ranges and 0.5–2 FIC, indicating no synergy. At 40–80 µg riboflavin, there was two-fold reduction in bacterial survival, with meropenem-riboflavin exhibiting significant reduction and FIC of 0.075 indicating high synergistic activity. Biofilm-formation was altered (from strong to weak phenotype) with 40 µg riboflavin-antibiotic treatment. There was a 40–70% reduction in bacterial survival in THP-1 cells treated with meropenem-riboflavin after 3 hours, and complete clearance between 24-48 hpi. Riboflavin potentiated fluoroquinolones and meropenem, leading to modulation of the host immune response for the clearance of the strains.

Background/objectives: The health benefits of resistant starch are well known, but there have not been many studies available documenting the effect of basmati rice products containg resistant starch upon blood glucose level and lipid profile in vivo efficacy. Methods: Common cooking methods were used to prepare basmati rice products including two boiling methods viz. boiling 1 (boiling by absorption), boiling 2 (boiling in extra amount of water), frying and pressure cooking. The cooked rice were held at various temperatures and times: it was made fresh (T1), kept at room temperature (20–22°C) for 24 h (T2), kept at 4°C for 24 h (T3), and then reheated after being kept at 4°C for 24 h(T4). Next, the products' proximate composition, total dietary fibre (soluble and insoluble), resistant starch (RS), and In vitro starch digestion rate (rapidly and slowly digested starch) were examined. The effect of RS on blood glucose and lipid profile were measured in humans and rats. Histopathological study of liver and pancreas in rats were also observed. Results: The basmati rice prepared by boiling 1 and stored with T3 was found more effective to control blood glucose and lipid profile. Similarly in rats, the blood glucose level, cholesterol, triglycerides and LDL were reduced about 29.7, 37.9, 31.3 and 30.5% respectively, after consumption of basmsti rice prepared by boiling 1 and stored at T3. Conclusion: Rice products stored at 4⁰C have a high amount of resistant starh, insoluble dietary fibre, slowly digestible starch and low glycemic index. Thus helps to inhibit glycogen and lipid synthesis.

The eutrophication of open water bodies, especially in coastal water area, has received intensive public focuses in recent years. Biological treatment of organic pollutants in industrial and domestic wastewater requires microbial flora to participate. The environmental impact of these microbes, particularly in regard to the spread of antibiotic resistance genes and pathogenicity in coastal water, remains largely unknown. We initiate studies to examine antibiotic resistance genes (ARGs) in microbial flora and study the mode of antibiotic spread in the coastal waters of Bohai Bay, North China by using high performance liquid chromatography-mass spectrum analysis and quantitative polymerase chain reaction. The metabolic features of bacteria related to the presence of ARGs in the coastal area showed the enrichment of Pseudomonadale species with triple resistance properties (ampicillin, kanamycin and gentamycin) at the estuary site locating adjacent to a coastal sewage treatment plant where both type I and type II polyketide synthase genes and b-lactam type antibiotics are detected. Pseudomonadale order is phylogenetically belonged to Proteobacteria Phylum, Gamma-proteobacteria Class and contains Pseudomonadaceae family and Pseudomonas genus. QPCR analysis suggests that the percent occupation of Pseudomonadale species to total Proteobacteria in the examined stations is close to several sampling stations close to sewage treatment plants, where consistent release of organic wastes occurred.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Under the increasingly severe global heat threat, continuous high temperature has far-reaching effects on plant growth and development and become a major constraint to crop production. The development of heat-resistant varieties has become research hotspot in many fields, and it is also necessary to establish effective identification methods. In this study, twenty Brassica rapa varieties were selected to to investigate the physiological and biochemical characteristics under heat stress, explore the relationship between physiological response and the heat resistance mechanism, select some typical heat-resistant and heat-sensitive varieties. The effects of photosynthetic electron transfer and antioxidant pathway on heat resistance of Brassica rapa were identified. These findings will providing an important reference for the physiological regulation and identification method of high-temperature stress in plants.

The $k$-means problem is to compute a set of $k$ centers (points) that minimizes the sum of squared distances to a given set of $n$ points in a metric space. Arguably, the most common algorithm to solve it is $k$-means++ which is easy to implement, and provides a provably small approximation factor in time that is linear in $n$. We generalize $k$-means++ to support: (i) non-metric spaces and any pseudo-distance function. In particular, it supports M-estimators functions that handle outliers, e.g. where the distance $\mathrm{dist}(p,x)$ between a pair of points is replaced by $\min {\mathrm{dist}(p,x),1}$. (ii) $k$-means clustering with $m\geq 1$ outliers, i.e., where the $m$ farthest points from the $k$ centers are excluded from the total sum of distances. This is the first algorithm whose running time is linear in $n$ and polynomial in $k$ and $m$.

Candida glabrata is a yeast of increasing medical relevance, particularly in critically ill patients. It is the second most isolated Candida species associated with invasive candidiasis (IC) behind C. albicans. The attributed higher incidence is primarily due to an increase in the acquired immunodeficiency syndrome (AIDS) population, cancer, and diabetes patients. The elderly population and the frequent use of indwelling medical devices are also predisposing factors. The work aimed to review various virulence factors that facilitate the survival of pathogenic C. glabrata in IC. The available published research articles related to the pathogenicity of C. glabrata were retrieved and reviewed from four credible databases, mainly Google Scholar, ScienceDirect, PubMed, and Scopus. The articles highlighted many virulence factors associated with pathogenicity in C. glabrata, including adherence to a susceptible host surface, evading host defences, and producing hydrolytic enzymes (e.g., phospholipases, proteases, and haemolysins). The factors facilitate infection initiation. Other virulent factors include iron regulation and genetic mutations. Accordingly, biofilm production, tolerance to high-stress environments, and development of resistance to the antifungal drug, notably to fluconazole and other azole derivatives, were reported. The review provided evident pathogenic mechanisms and antifungal resistance associated with C. glabrata in ensuring its sustenance and survival.

Multidrug resistant extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is considered a serious concern to public health worldwide including Bangladesh, and chicken meat is recognized as an important reservoir of ESBL-Ec dissemination to humans. Therefore, this study aimed to determine the prevalence, and phenotypic and genotypic antimicrobial resistance pattern of ESBL-producing Escherichia coli (ESBL-Ec) in frozen chicken meat. A total of 113 frozen chicken meat samples were purchased from 40 outlets of 9 branded supershops in five megacities in Bangladesh. Isolation and identification of Escherichia coli were done based on cultural, biochemical properties and PCR assay. The resistance pattern was determined by disk diffusion method. ESBL-encoding genes were determined by multiplex PCR. The results showed that 76.1% samples were positive for Escherichia coli, of which 86% were ESBL producers. All the isolates were multidrug-resistant (MDR). Resistance to 9–11 and 12–13 antimicrobial classes was observed in 38.4% and 17.4% isolates, respectively while only 11.6% were resistant to 3–5 classes. The possible extensively drug resistance (pXDR) was found in 2.3% isolates. The high single resistance was observed for oxytetracycline (93%) and amoxicillin (91.9%), followed by ampicillin (89.5%), trimethoprim-sulphamethoxazole and pefloxacin (88.4%), and tetracycline (84.9%). Most importantly, 89.6% of isolates were resistant to carbapenems. All the isolates were positive for blaTEM gene. However, the blaSHV and blaCTX-M-2 genes were identified in two ESBL-non producer isolates. None of the isolates were carried blaCTX-M-1 gene. This study provided evidence of wide dissemination of MDR and existence of pXDR ESBL-Ec in frozen chicken meat in Bangladesh. Our data clearly indicated that frozen chicken meat is, at the present time, the most significant known food source of ESBL-Ec to which peoples are regularly exposed.

Antimicrobial resistance (AMR) is a major global concern; antibiotics and other regular treatment methods have failed to overcome the increasing number of infectious diseases. Bacteriophages (phages) are viruses that specifically target/ kill bacterial hosts without affecting other human microbiome. Phage therapy provides optimism in the current global healthcare scenario with a long history of its applications in humans that has now reached various clinical trials. Phages in clinical trials have specific requirements of being exclusively lytic, free from toxic genes with an enhanced host range that adds an advantage to this requisite. This review explains in detail the various phage engineering methods and their potential applications in therapy. To make phages more efficient, engineering has been attempted using techniques like conventional homologous recombination, Bacteriophage Recombineering of Electroporated DNA (BRED), clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, CRISPY-BRED/Bacteriophage Recombineering with Infectious Particles (BRIP), chemically accelerated viral evolution (CAVE), and phage genome rebooting. Phages are administered in cocktail form in combination with antibiotics, vaccines, and purified proteins, such as endolysins. Thus, phage therapy is proving to be a better alternative for treating life-threatening infections, with more specificity and fewer detrimental consequences.

With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance (AMR), databases and clear nomenclature for AMR gene families are critical. Due to the convoluted nomenclatural history of the integron-associated trimethoprim-resistant dihydrofolatereductase (dfr) gene family, we decided to conduct a literature review, comparative sequence analysis, and phylogenetic investigation of the dfr family, the results of which are presented here and available at the Comprehensive Antibiotic Resistance Database (CARD). Overall, literature review and phylogenetic analysis resolved gene name synonyms based on sequence. We recommend adoption of phylogenetic methods to help guide AMR gene naming efforts and relegation of misleading names to synonyms.

Beetles are by far one of the most successful and diverse insect species. A part of this success is attributed to their elytra which provide various functions such as protection to their bodies from mechanical forces and the harmful environmental factors. In this study, Stag beetle (Lucanus cervus) elytra were first examined for their overall flexural properties and were observed to have a localized shape retaining snap-through mechanism which could play a crucial role in energy absorption, e.g. during battles and falls from heights. The snap-through mechanism was validated using theoretical calculations and also finite element simulations. Elytra were also characterized to examine their puncture and wear resistance. Our results show that elytra resisted puncture up to a force of 1.8±0.4 N and have puncture resistance compared to that of commercially available puncture resistant gloves. The measured values of modulus and hardness of elytra exocuticle were 10.3±0.8 GPa and 0.7±0.1 GPa. Using the hardness to modulus ratio as an indicator of wear resistance, the estimated value was observed to be in the range of wear resistant biological materials. Thus, our study demonstrates different mechanical properties of the stag beetle elytra which can be explored to design shape retaining bio-inspired composites with enhanced puncture and wear resistance.

Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increase rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarises the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage -antibiotic combination therapy, phage coding Acinetobacter baumannii and the novel phage enzyme treatment. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions especially in regard to its in vivo applications, before possible routine clinical use.

Natural cellulose hydrogels have been widely used to enhance mechanical properties. However, existing natural fiber composite hydrogels are not reusable, limiting their potential applications. To address this issue, we designed and prepared a polyvinyl alcohol/glycerol /bamboo microfibril double network tough hydrogel using a simple method. The bamboo microfibril and polyvinyl alcohol form a tight and rigid network through hydrogen bonding, improving mechanical properties. The prepared polyvinyl alcohol/glycerol/bamboo microfibril double network tough hydrogel has the advantages of reusability and fatigue resistance. Furthermore, both the elastic modulus and toughness of the hydrogel increase with increasing bamboo microfibril content. We also demonstrated that the hydrogel can be recast after cyclic compression, maintaining its recyclability, stability, and certain stiffness and toughness. Our study highlights the potential of hydrogels for controllable mechanical properties, fatigue resistance and shows that polyvinyl alcohol/glycerol/bamboo microfibril hydrogel has broad value for plasticity and reuse.

The majority of E-commerce transactions reveal private information such as customers' identities, order contents, and payment information during the transaction. Other personal information such as health conditions, religion, and even ethnicity may be also deduced. Even when deploying electronic cryptocurrencies such as Bitcoin, anonymity cannot be fully guaranteed. Also, many anonymous payment schemes suffer from possible double spending circumstances. E-commerce privacy is basically a difficult problem as it involves parties with concurring interests. Three major e-commerce requirements are highly difficult to resolve: anonymous purchase, anonymous delivery, and anonymous payment. This work presents a possible e-commerce system addressing all three anonymity requirements for electronic-items business on open networks. The system offers anonymous entities authentication mechanisms up to completing a fair anonymous e-commerce transaction. The system is based on deploying a physically clone-resistant hardware token for each relevant involved party. The tokens are made clone-resistant by accommodating a Secret Unknown Cipher (SUC) in each hardware-token as a digital PUF-like identity. A set of novel generic system-setups for units, protocols and e-commerce schemes is introduced. The proposed anonymization is basically attained by virtually-replacing relevant e-commerce entities by low-cost, unique and clone-resistant tokens/units using SUCs. The units act as trustable anonymous, authenticated and non-replaceable entities monitored by their acting users.

In the continued battle against one of the oldest enemies known to mankind, Mycobacterium tuberculosis (MTB), the emergence of drug resistance among children poses multiple challenges for early detection and treatment. Molecular diagnostics and newer drugs like bedaquiline and delamanid have strengthened the armamentarium and helped design convenient, safe and child-friendly therapeutic regimens against drug-resistant tuberculosis (TB). Preventive strategies like treatment of TB infection among children living in close contact with patients with drug-resistant TB and effective vaccines against TB are currently in the investigative stages of development and implementation. In addition to the implementation of recent novel diagnostics and treatment modalities, effective psychosocial and nutritional support, as well as dedicated monitoring for compliance and adverse effects, are crucial determinants for successful treatment outcomes in these children.

The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G>A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

Fermented food products are widely consumed for their nutritional and health-promoting properties earning them a central place in diets around the globe. However, these foods can present a paradox, as they have the potential to harbor not only beneficial probiotics but also antibiotic-resistant (AR) microbes and genes. The impact of AR in fermented foods has far-reached implications, such as its potential effects on human health, repercussions in the food industry, and environmental consequences. An in-depth analysis of AR in fermented foods, including dairy products, fermented fruits and vegetables, meat products, and beverages, would provide insights into the extent and ramifications of the issue with these foods. Therefore, this review systematically presents the status of AR in fermented foods, with a particular focus on AR bacteria and genes within this category of food products. The review also highlights the complexities of AR in fermented foods, emphasizing the role of bacterial adaptation during the fermentation process and the dynamics of bacterial gene transfer. Various contributing factors to AR are brought into focus, including intrinsic resistance among bacteria in fermented foods and the potential risk of contamination with pathogenic bacteria. Moreover, this review presents a range of mitigation strategies, from the development of novel antimicrobials to advances in fermentation technology and regulatory control. This comprehensive perspective on the intricate interplay between AR and fermented food will potentially pave the way for more targeted research and mitigation strategies in this critical area.

Nutrigenomics is the study of the interaction of nutrition and genes, focusing on the influence of nutrients on the genome, proteome, and metabolome, and how nutrition affects human health. In the context of nutrigenomics, bioactive components are dietary ingredients that may transmit information from the external environment and alter gene expression in the cell, and hence the overall function of the organism. It is critical to consider food not only as a source of energy and essential nutrients necessary for life and growth, but also as a factor impacting health/disease, biochemical processes, biochemical pathway activation and affecting the diversity of the gut microbiome. Antimicrobial resistance in pathogenic and commensal microorganisms has emerged as a major public health concern due to emerging antimicrobial resistance genes in E. coli isolates from pig, cattle, chicken, and turkey meat, against tetracycline, streptomycin, and sulfonamides. Also, Salmonella spp. and Campylobacter spp. have shown antibiotic resistance at farms and slaughterhouses, and in animal-based food products. A correlation has been proven between a critical nutrient-responsive signaling system and catabolite control of gene expression, and a two-component signaling system that drives antibiotic resistance in E. faecalis, revealing a previously unknown integration between the nutritional status of the cell and intrinsic antibiotic resistance. Moreover, different nutrigenomic approaches can be applied to mitigate possible emergence of antimicrobial resistance against novel antibiotics. However, little progress has been achieved in converting nutrigenomics information into clinical advice, so far.

Pseudomonas aeruginosa is a critical healthcare challenge due to its ability to cause persistent infections and the acquisition of antibiotic resistance mechanisms. Lack of preventive vaccines and rampant drug resistance phenomenon has rendered patients vulnerable. As new antimicrobials are in the preclinical stages of development, mining for the unexploited drug targets is also crucial. Here, we designed a chimeric vaccine against P. aeruginosa using a subtractive proteomics approach and identified nine unique enzymes as novel drug targets in PAO1 proteome. A total of five unique proteins were selected as potential vaccine candidates based on essentiality, extracellular localization, virulence, antigenicity, pathway association, protein-protein interaction analysis, hydrophilicity, and low molecular weight. These include two outer membrane porins OprF (P13794) and OprD (P32722), a protein activator precursor pra (G3XDA9), a probable outer membrane protein precursor PA1288 (Q9I456), and a conserved hypothetical protein PA4874 (Q9HUT9). These proteins were further analyzed using a reverse vaccinology approach to identify immunogenic and antigenic T cell and B cell epitopes. The best scoring epitopes qualifying for all set criteria were then further subjected to the construction of a polypeptide multi-epitope vaccine construct with cholera toxin B (CtxB) subunit as an adjuvant. The identified drug targets qualifying the screening criteria were: UDP-2-acetamido-2-deoxy-d-glucuronic acid 3-dehydrogenase WbpB (G3XD23), aspartate semialdehyde dehydrogenase (Q51344), 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase (Q9HV71), 3-deoxy-D-manno-octulosonic-acid transferase (Q9HUH7), glycyl-tRNA synthetase alpha chain (Q9I7B7), riboflavin kinase/FAD synthase (Q9HVM3), aconitate hydratase 2 (Q9I2V5), probable glycosyltransferase WbpH (G3XD85) and UDP-3-O-[3-hydroxylauroyl] glucosamine N-acyltransferase (Q9HXY6). For druggability and pocketome analysis crystal and homology structures of these proteins were retrieved and developed. A sequence-based search was performed in different databases (ChEMBL, Drug Bank, PubChem and Pseudomonas database) for the availability of reported ligands and tested drugs for the screened targets. These predicted targets may provide a basis for the development of reliable antibacterial preventive and therapeutic options against P. aeruginosa.

Klebsiella pneumoniae, a major cause of both hospital and community-acquired infections, is listed by the World Health Organization as a critical priority antibiotic- resistant bacterial pathogen. With the appearance of sequencing techniques such as Next-generation Sequencing (NGS), there is the possibility to obtain the whole genome of the bacteria, getting to know all antimicrobial resistance determinants. The purpose of this study has been to apply this new technology to clinical microbiology, in order to characterize the resistome present in carbapenem-resistant K.pneumoniae strains isolated in a tertiary hospital in Valencia, Spain. A total of 234 isolates were prepared for whole-genome sequencing with Ilumina MiSeq, and sequences were later studied for antimicrobial resistance genes, sequence-typing and plasmids. Sequence-typing showed four major circulating clones in our hospital settings: ST11, ST307, ST101 and ST147, carrying different plasmids and different resistance determinants such as OXA-48 and NDM-1 carbapenemase. Application of new technologies such as whole-genome sequencing in clinical microbiology gives advantages when it comes to rapid therapy adjustment, consequently improving the patient’s clinical outcomes.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Salmonella can cause acute and chronic infections in humans. Salmonella species are known to cause food poisoning and other diseases in developing countries. Their role in the pathogenesis of these diseases has received increased international attention. Despite numerous advances in sanitation, they still can infect humans and cause outbreaks in developed countries. For example, Salmonella causes about 1.2 million illnesses in the US each year with over 450 deaths. Additionally, Salmonella outbreaks cause significant losses to chicken producers globally. The Salmonella species is also prone to acquiring resistance to various classes of antibiotics. Hence, the need for a paradigm shift from antibiotics to bacteriophages to manage, control and treat bacterial infections. The ɛ34 phage belongs to Podoviruses and categorized into the P22-like phages. The P22-like phages include ɛ34, ES18, P22, ST104, and ST64T. In this work, we investigated the antibacterial property of ɛ34 phage tailspike protein against Salmonella newington (S. newington). We demonstrate here that, the phage’s tailspike protein enzymatic property as a LPS hydrolase synergizes with Vero Cell culture supernatant in killing S. newington. Using decellularized cartilage scaffold as an ex vivo tissue model, the ɛ34 TSP protected the scaffold from S. newington biofilm formation. Computational analysis of the ɛ34 TSP interaction with membrane proteins of S. newington demonstrated a higher probability (0.7318) of binding to ompA of S. newington, and when docked to ompA extracellular component, it produced a high free energy of -11.3kcal/mol. We also demonstrate the resistance/sensitivity of the tailspike to the digestive enzyme trypsin. The data obtained in this work indicates that the trypsin resistant tailspike protein of Ɛ34 phage can be formulated as a novel antibacterial agent against S. newington.

Background: Carbapenem-resistant A. baumannii (CRAB) hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) is becoming a globally therapeutic problem. Method: The open-label, randomized, superiority, single-blind trial was conducted in Rajavithi Hospital, a super-tertiary care in Bangkok, Thailand. We included CRAB HAP/VAP patients randomly assigned to receive sitafloxacin-colistin-meropenem compared to colistin-meropenem to assess mortality, clinical response, and adverse effects. Result: April 2021-2022, 77 patients were randomized and received combination treatment sitafloxacin-colistin-meropenem (n = 40) or colistin-meropenem (n = 37). Among two groups, the all-cause mortality rate was no significant difference at 7-days and 14-days (7.5% vs 2.7%; p = 0.616 and 10% vs 10%; p = 1, respectively). Patients received sitafloxacin-colistin-meropenem showed improved clinical response, compared patients receiving colistin-meropenem with both intentions to treat (87.5% vs 62.2%; p = 0.016) and per-protocol analysis (87.2% vs 67.7%; p = 0.049). The adverse effects were not different among 2 groups. Conclusion: Adding sitafloxacin as third agent in meropenem plus colistin could improve clinical in CRAB HAP/VAP with comparable adverse effects. Sitafloxacin-meropenem-colistin could be another option for combatting CRAB HAP/VAP

The article presents the results of research on the production of effective inorganic fillers and chemically resistant composite polymer-mineral materials based on industrial waste. The aim of the work is to develop the technological foundations for the production of inorganic fillers and highly filled filling compositions for use in chlorine-containing media. Materials with high resistance to hydrochloric acid are graphite and quartz sand. Thermal power plant (TPP) ash was used as an acid-resistant filler in the compositions. The simplex lattice planning method was used to determine the areas of compositions with the best properties. Two components were selected: formaldehyde rubber resin and mineral filler (TPP ash) as a binder. As the third component, hydrolytically active fillers were used - anhydrite, phosphogypsum and phosphorus production slag. A preliminary operation was performed to remove hygroscopic moisture from the filler.The influence of the nature of mineral fillers on the chemical stability and durability of the obtained composites is investigated. The nature of the interaction of mineral fillers with a polymer binder was determined, and chemical interaction of the hydroxyl groups of the filler and the methyl groups of the polymer took place. The mathematical planning method was used to optimize the chemical resistance and durability of the compositions of the studied substances. Based on the results of this study, optimal compositions of compositions, anhydrite, phosphogypsum and phosphoric slag were selected. These composites, with the highest possible degree of filling, have high target characteristics.

Multidrug resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach; we have modified the antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-ester-PPh3), to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3 and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (MRSA) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with an MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivates induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria, through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.

The 2019-Novel Coronavirus has currently gripped the world in terror, affecting 210 countries and territories. Originating from Wuhan, Hubei province, China, the virus has spread so rapidly throughout the world and has already claimed 308,927 lives and is currently afflicting 4.6 million people. The US has over 1.48 million confirmed cases of COVID-19, followed by Spain, Italy, France, UK, Germany, Turkey, Russia, Iran, and China. On careful inspection of the COVID-19 statistics, a peculiar unsettling trend becomes apparent. Western European countries and the US appear to have difficulties in overcoming the catastrophe. In contrast, countries in East Asia, Middle East and mid-Europe have sorted out the situation. Here, we will highlight this trend and propose the importance of infection-genomics (sankramikogenomics), in understanding the susceptibility to COVID-19 and the severity of disease progress. More detailed, systematic evaluation may also identify more susceptible populations. We will also highlight mere 12-fold lower affinity is insufficient to ignore CD147, as interactions occur between tens of spike proteins and equal number of cell surface ACE2 and/or CD147. Thus, both receptors are important to understand sankramikogenomics and severity of COVID-19. The observed ethnic differences in COVID severities may be due to variations in structure or tissue-specific expression (alternate splicing and accessibility) of both the target receptors. Research on both receptors may help in designing improved therapeutic strategies to fight COVID-19. Similar to pharmacogenomics to drug development and precision medicine, Sankramikogenomics will become an important field in other infectious diseases and pathogenicity.

We studied short- and long-term effects of intravitreal injection of N-methyl-D-aspartate (NMDA) on melanopsin-containing (m⁺) and non-melanopsin-containing (Brn3a⁺) retinal ganglion cells (RGCs). In adult SD-rats, the left eye received a single intravitreal injection of 5µL of 100nM NMDA. At 3 and 15 months, retinal thickness was measured in vivo using SD-OCT. Ex vivo analyses were done at 3, 7, 14 days or 15 months after damage. Whole-mounted retinas were immunolabelled for Brn3a and melanopsin, the total number of Brn3a⁺RGCs and m⁺RGCs were quantified and their topography represented. In control retinas, the mean total numbers of Brn3a⁺RGCs and m⁺RGCs were 78,903±3,572 and 2,358±144 (mean ± SD; n=10), respectively. In the NMDA injected retinas, Brn3a⁺RGCs numbers diminished to 50% and 25%, at 3 and 14 days, respectively, but there was no further loss up to 15 months. The number of immunoidentified m⁺RGCs decreased significantly at 3 days, recovered between 3-7 days and was back to normal thereafter. OCT measurements revealed a significant thinning of the left retinas at 3 and 15 months. Intravitreal injections of NMDA induce a rapid loss of 75% of Brn3a⁺RGCs, a transient downregulation of melanopsin expression but not m⁺RGC death, and a thinning of the inner retinal layers.

At secondary healthcare, Carbapenem-Resistant Enterobacterales (CREs) such as observed in Klebsiella pneumoniae are a global public health priority with significant clinical outcomes. In this study, we describe clinical, phenotypic, and genotypic characteristics of three pan-drug resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for acquisition of multidrug resistant organisms while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents such as ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria including CREs pointing towards potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial resistant genes (ARGs), including blaNMD-5 and blaOXA derivative types as well as a mutated outer membrane porin protein (OmpK37).

BMAP-18, derived from the N-terminal region of bovine myeloid antimicrobial peptide BMAP-27, demonstrated potent antimicrobial activity without cytotoxicity. This study aimed to compare the antibacterial, antibiofilm, and anti-inflammatory properties of BMAP-18, rich in aromatic phenylalanine residues, with its aliphatic analogue, BMAP-18-FL. Both aromatic BMAP-18 and aliphatic BMAP-18-FL exhibited equally potent antimicrobial activities against Gram-positive and Gram-negative bacteria, particularly methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Mechanistic investigations employing SYTOX green uptake, DNA binding, and FACScan analysis revealed that both peptides acted by inducing membrane permeabilization and subsequent intracellular targeting. Moreover, both BMAP-18 and BMAP-18-FL effectively prevented biofilm formation and eradicated existing biofilms of MRSA and MDRPA. Notably, BMAP-18-FL displayed superior anti-inflammatory activity compared to BMAP-18, significantly reducing the expression levels of pro-inflammatory cytokines in lipopolysaccharide-stimulated macrophages. This study emphasizes the similarities and differences in the antimicrobial, antibiofilm, and anti-inflammatory properties between aromatic BMAP-18 and aliphatic BMAP-18-FL, providing valuable insights for the development of multifunctional antimicrobial peptides against drug-resistant bacteria.

Antibiotics are released into the environment either directly in an unchanged form or in a partially metabolized form. The discharge is usually through untreated waste or industrial treatment effluents. The potential concern is the uptake of these antibiotics by crops irrigated by treated wastewater. This study collected wastewater from eight points at the Pagla, Kadamtali, Dhaka treatment plant. Here we consider three crucial antibiotics, Doxycycline, Ciprofloxacin, and Tetracycline, used mainly during the last two years of the pandemic. A PDA detector was used in high-performance liquid chromatography (HPLC) analysis to determine the raw and processed effluent antibiotics. The most frequently seen antibiotics in natural wastewater were Doxycycline and Ciprofloxacin, with the highest concentration of 0.23µgL-1and 0.20 µgL-1(raw water), respectively. Tetracycline was not detected in natural water. Contrarily, Doxycycline was discovered in the Pagla plant's completed water and had the highest concentration (0.12 gL-1), whereas Ciprofloxacin and Tetracycline were not found in the dead water. The findings of this study showed that Doxycycline was still present in both the raw and processed effluent. Both natural and finished wastewater was subjected to a microbial-resistant test in the presence of all three antibiotics. The results revealed that the samples detected both heterotrophic bacteria and total coliform. The viable aerobic heterotrophic bacteria ranged between 5.421 and 4.754 log cfu/ml. Total bacteria load gradually decreased in the finished wastewater.

(1) Background: Although resistance to pathogens and pests has been researched in many potato cultivars and breeding lines with DNA markers, there is scarce evidence as to the efficiency of the marker-assisted selection (MAS) for these traits when applied at the early stages of breeding. A goal of this study was to estimate the potential of affordable DNA markers to track Rpi disease resistance genes, that are effective against the pathogen Phytophthora infestans, as a practical breeding tool on a progeny of 68 clones derived from a cross between the cultivar Sudarynya and 13/11-09. (2) Methods: this population was studied for four years to elucidate the distribution of LB resistance and other agronomical desirable or simple to phenotype traits such as tuber and flower pigmentation, capacity and structure of yield. LB resistance was phenotypically determined through natural and artificial infection and the presence/absence of nine Rpi genes was assessed via 11 sequence-characterized amplified region (SCAR) markers. To aid this analysis, the profile of Rpi genes in the 13/11-09 parent was established using diagnostic resistance gene enrichment sequencing (dRenSeq) as a gold standard. (3) Results: at the early stages of a breeding program, MAS can halve the workload when screening the segregation of F1 offspring and selected SCAR markers for Rpi-genes provide useful tools.

Bacterial resistance to antibiotics is a growing global concern, threatening human and environ-mental health, particularly among urban populations. Wastewater treatment plants (WWTPs) are thought to be “hotspots” for antibiotic resistance dissemination. The conditions of WWTPs, in conjunction with the persistence of commonly used antibiotics, may favor the selection and trans-fer of resistance genes among bacterial populations. WWTPs provide an important ecological niche to examine the spread of antibiotic resistance. We used heterotrophic plate count methods to identify phenotypically resistant cultivable portions of these bacterial communities and charac-terized the composition of the culturable subset of these populations. Resistant taxa were more abundant in raw sewage and wastewater before the biological aeration treatment stage. While some antibiotic resistant bacteria (ARB) were detectable downstream of treated wastewater re-lease, these organisms are not enriched relative to effluent-free upstream water, indicating effi-cient removal during treatment. Combined culture-dependent and culture-independent analyses revealed a stark difference in community composition between culturable fractions and the envi-ronmental source material, irrespective of culturing conditions. Higher proportions of the envi-ronmental populations were recovered than predicted by the widely accepted 1% culturability paradigm. These results represent baseline abundance and compositional data for ARB commu-nities for reference in future studies addressing the dissemination of antibiotic resistance associ-ated with urban wastewater treatment ecosystems.

Tumor cells exhibit a resistance-associated secretory phenotype involving extracellular vesicles (EVs) and heat shock proteins (HSPs). This response occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as in free form as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in stressome release, epithelial-to-mesenchymal transition (EMT), and tumor progression. A number of HSP family members and their common receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein species. The small EVs (30 to 200 nm in size, potentially exosomes) were released even in a non-heated condition from the prostate cancer cells, whereas EMT-coupled release of EVs (200 to 500 nm, likely ectosomes) with associated HSP90α was increased after heat shock stress (HSS). Lactate dehydrogenase, a marker of membrane leakage/damage of cells, was also released upon HSS from the prostate cancer cells. During this stress response, intracellular CDC37 was also transcriptionally inducible by heat shock factor 1, and knockdown of CDC37 decreased EMT-coupled release of EVs. Triple knockdown of CDC37, HSP90α, and HSP90β was required for efficient reduction of the chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, the data indicated that CDC37 and HSP90 are essential for stressome release and for tumorigenesis in resistant cancer.

Fire safety is a critical concern in various industries necessitating the development of sustainable and effective fire-resistant materials. Sustainable fire-resistant polysaccharide-based composite aerogels are regarded as innovative solutions in fire safety applications, and as such, research in this field has increased consistently over the past few years. Despite the plethora of literature on this important subject, only a few studies have attempted to map the global research of sustainable fire-resistant polysaccharide-based composite aerogels to identify the geospatial collaborative network and trend of research. This study utilizes a scientometric review of global trends in sustainable fire-resistant polysaccharide-based composite aerogels research between 2003–2023 by VOSviewer and biblioshiny to analyze co-author, co-word, co-citation, clusters, and geospatial map. A total of 234 bibliographic records from the Scopus database were analyzed to generate the study's research power networks and geospatial map. The most significant contributions in sustainable fire-resistant polysaccharide-based composite aerogels comes from China, the United States, Australia, Canada, and India with records of 194, 20, 11, 9, and 8 respectively. The top five sources for articles in this area of research include ACS Applied Materials and Interfaces, Chemical Engineering Journal, Composite Engineering, ACS Sustainable Chemistry and Engineering, and Carbohydrate Polymers. The application of sustainable fire-resistant polysaccharide-based composite aerogels spans the engineering and construction fields. The versatility in the fabrication and customization allows for seamless integration into diverse applications. The article concludes by emphasizing the significance of sustainable fire-resistant polysaccharide-based composite aerogels as a promising advancement in fire safety technology, combining sustainability, fire resistance, versatility, and mechanical strength to address critical challenges in the field. This study provides readers with an extensive understanding of the salient research themes, trends, and patterns of sustainable fire-resistant polysaccharide-based composite aerogel research worldwide.

The cerebellum is an encephalic region classically known for its central role in the control of movement, although recent research has revealed its involvement in other cognitive and affective tasks. Several different pathologies are known to affect this structure, causing a wide range of behavioral and gait impairments. Intriguingly, although the neurodegenerative factors affect all Purkinje cells of the cerebellum uniformly, certain neurodegeneration patterns can be distinguished, in which some Purkinje cells persist longer than other cell types. Precisely, there is a cerebellar region, lobe X, which is more resistant to different types of neurodegeneration regardless of the injury. This work will review the main models of cerebellar degeneration, with special emphasis on this region, and aims to reveal a common origin for its resistance to neuronal death.

Introduction Infections caused by multidrug-resistant bacteria (MDR) occur more frequently after pancreaticoduodenectomy (PD) compared to other abdominal surgeries, and infective complications are a leading cause of postoperative morbidity following PD. Pre-operative biliary stent (PBS) placement often leads to biliary contamination, which in turn plays a significant role in postoperative infections. The aim of this study is to evaluate the impact of MDR contamination on short-term postoperative outcomes in patients undergoing PD and to examine the relationship between MDR bacteria, PBS, and bile contamination. Methods This is a retrospective study based on a prospectively maintained database comprising 825 consecutive patients who underwent pancreaticoduodenectomy (PD) between January 2010 and December 2020 at our center. All procedures were conducted with a standardized resection by a dedicated group of surgeons in a specialized pancreatic surgery unit, and the patients were managed according to the same perioperative enhanced recovery protocol. Results MDR bacteria were present in 17.5% of bile cultures, exclusively within the stented group. In our multivariate analysis, the development of a major postoperative complication (MPC) was correlated with the presence of MDR bacteria in the bile (OR 1.66, 95% CI: 1.1-2.52; p = 0.02). MDR bacteria were detected early in the surgical drainage in 144 out of 825 patients (12.1%), with 72.2% having a previous biliary stent placement and 27.8% without stents (p < 0.001). In our multivariate analysis, the development of an MPC was associated with the presence of MDR bacteria in the drainage (OR=1.81, 95% CI: 1.21-2.73, p= 0.0042). Conclusions We demonstrated that MDR contamination worsens the short-term outcomes of patients undergoing PD. Specifically, when MDR bacteria are present in both the bile and drainage, there is a statistically significant increase in the incidence of major postoperative complications (MPC). Our data suggest that the majority of MDR surgical site infections stem from biliary contamination resulting from the placement of a pre-operative biliary stent (PBS).

There is a major problem with the rising occurrence of highly virulent and multiply-resistant strains, including methicillin-resistant Staphylococcus aureus (MRSA), because of their difficult treatment. This study aimed to evaluate the antibacterial and antibiofilm effect of new enterocins (Ent) against potential pathogenic MRSA strains isolated from rabbits. Staphylococci (n =110) were identified with PCR and screened for methicillin/oxacillin/cefoxitin resistance (MR) using the disk diffusion method and the PBP2' Latex Agglutination Test Kit. Enzyme production, hemolysis, DNase activity, slime production, and biofilm formation were tested in MRSA strains. The susceptibility of MRSA to eight partially-purified enterocins (Ent) produced by E. faecium and E. durans strains was checked using agar spot tests. The antibiofilm activity of Ents was tested using a quantitative plate assay. Out of 14 MRSA, PBP testing confirmed MR in 8 strains. The majority of MRSA showed DNase activity and β-hemolysis. Slime production and moderate biofilm formation were observed in all strains. MRSA were susceptible to tested Ents (100–12800 AU/mL; except Ent4231). The antibiofilm effect of Ents (except Ent4231) was noted in the high range (64.9-97.0%). These results indicate that enterocins offer a promising option for the prevention and treatment of bacterial infections caused by biofilm-forming MRSA.

This article describes the challenges, pharmacological strategies, and recommendations for managing multidrug-resistant breast cancer in Sub-Saharan Africa (SSA). By examining the current breast cancer treatment landscape, region-specific challenges, and promising pharmacological interventions, the objective is to bring to light the insufficient research on breast cancer and its multidrug resistance in this part of the world and guide healthcare professionals, policymakers, and researchers in developing evidence-based strategies for improved breast cancer care in SSA. Breast cancer is the leading cause of cancer morbidity in SSA, necessitating continuous advancements in its management. This overview explores the evolution of breast cancer treatment, including surgery, targeted therapy, immunotherapy, radiotherapy, and chemotherapy. Despite these advancements, multidrug resistance poses a significant challenge, impacting treatment efficacy and patient outcomes.The article provides insights into various breast cancer treatment modalities, emphasizing surgery, targeted therapy, immunotherapy, radiotherapy, and chemotherapy. Each approach is discussed in detail, highlighting its significance in managing breast cancer. The effectiveness of these treatments is contingent on timely diagnosis and intervention. Multidrug resistance is examined as a critical obstacle in breast cancer treatment, elucidating its impact on treatment failure and patient outcomes. Mechanisms such as the efflux system, enhanced DNA repair, apoptosis inhibition, alterations in drug targets, and the tumor microenvironment contribute to multidrug resistance, emphasizing the need for a multifaceted understanding.The unique challenges faced in SSA regarding multidrug-resistant breast cancer are delineated. These include the lack of comprehensive data, late presentation and diagnosis, poor genomic studies, limited access to specialized care, financial constraints, inadequate infrastructure, and psychosocial support issues. Addressing these challenges is crucial for devising effective strategies. In response to multidrug resistance, the article discusses contemporary treatment strategies such as P-glycoprotein inhibitors, combined chemotherapy, and immunotherapy. Notable advancements, including the use of Tariquidar and synergistic effects of combined chemotherapy, are highlighted, presenting promising avenues for overcoming resistance.The article proposes recommendations to enhance breast cancer management in SSA, encompassing strengthening primary healthcare services, creating specialized oncology facilities and long-term monitoring and data collection. Breast cancer management in SSA is multifaceted, marked by challenges and evolving solutions. Multidrug resistance remains a significant hurdle, demanding a holistic approach. Promising advancements in pharmacological interventions offer hope, while comprehensive recommendations serve as a roadmap for progress. By implementing these strategies, SSA can substantially improve multidrug-resistant breast cancer care and overall patient well-being.

Imidacloprid, a neonicotinoid, has proven as efficacious against hemipterans including the brown planthopper, Nilaparvata lugens (Stål). Frequent use, however, has resulted in high levels of resistance to imidacloprid among brown planthopper populations. Endosymbionts of insects are important for host insect growth and development and seem to play a role in resistance to imidacloprid. In this study, polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) was used to analyze the bacterial and yeast-like-symbiont communities of imidacloprid-resistant and imidacloprid-susceptible brown planthopper populations. The Shannon-Weaver diversity index and the evenness index indicated that there were no differences in the composition of the symbiotic communities of resistant and susceptible with a similarity coefficient of 0.53 for bacterial symbionts and 0.56 for yeast-like symbionts for the two planthopper populations. Sequence comparison analysis showed that the numbers of bacterial species in the imidacloprid-resistant versus the imidacloprid-susceptible populations were not significantly different. The bacterial species in the susceptible population were members of the Enterobacteriaceae and Moraxellaceae, while these in the resistant population were members of the Enterobacteriaceae, Oxalobacteriaceae, Rhodobacteriaceae, and Sphingomonadaceae. The imidacloprid-susceptible population had more yeast-like symbiont species than the resistant population.

The use of anti-microbial drugs and coccidiostats in poultry farming is widespread, with a significant proportion of these drugs being excreted and released into the environment. The residues of such drugs in poultry litter (PL) can result in the development of antibiotic-resistant bacteria. The impact of different biotic treatments (aerobic, anaerobic, and stacking) on broiler litter (BL) before use as animal feed has not been studied extensively, nor have the differences between antimicrobial-dependent and independent broiler farms been investigated. This study aimed to determine the resistant bacteria in BL used as ruminant feed before and after litter treatment. The results showed that the most resistant bacteria before BL treatment were Enterococcus species. The study also found that the quantity of amoxicillin-resistant Enterococcus detected in samples from antimicrobial-dependent farms was significantly higher than in those from antimicrobial-independent farms. Additionally, 14% of bacteria were multi-resistant to tetracycline, sulfafurazole, and erythromycin in antimicrobial-independent farm litters, significantly lower than those measured in antimicrobial-dependent broiler farm litter. This study highlights the importance of better understanding, regulating, managing, and using animal waste appropriately to reduce the number of antibiotic-resistant bacteria and minimize the use of antimicrobials that carry high risks for animals, humans, and the environment

We survey the diversity of antimicrobial resistance profiles of Escherichia coli (E. coli) isolates and molecular genotypes by means of phylogenetic groups circulating in complex aquatic habitats, such as sewage and receiving waters bodies as well as in clinical environment in Boeotia regional district of Greece. The predominant resistant profile among all environmental and clinical isolates was to penicillins - ampicillin (AMP) and piperacillin (PIP). ESBLs resistance related profiles were observed both in environmental and clinical isolates. Phylogenetic group B2 was the predominant in clinical isolates, whilst group A was dominant in environmental isolates. We report that reclaimed river water and wastewater are reservoirs of R and MDR E. coli to commonly used antibiotics in clinical practice posing putative threats for human and animal health.

Infections with multi-drug-resistant (MDR) pathogens in food-animals threaten public health and food security. However, the epidemiology and factors associated with MDR Escherichia coli on Ugandan farms are not well known. This study investigated the prevalence, resistance patterns and factors associated with MDR E. coli carriage on chicken farms. A total of 158 E. coli strains were isolated from 158 chicken farms. The disc diffusion method for susceptibility testing was performed. Clinical breakpoints were interpreted according to Clinical and Laboratory Standards Institute guidelines. MDR was defined as resistance to three or more classes of antimicrobials. MDR E. coli prevalence on chicken farms was 62.7% (95% CI: 55.0 – 70.3). High resistance was observed against ampicillin 79.8% (95% CI: 72.7–85.4), tetracycline 72.8% (95% CI: 65.2–79.2), cotrimoxazole 55.7% (95% CI: 47.8–63.3), and ciprofloxacin 38% (95% CI: 30.7–45.9). Farmers who were males (APR = 0.72, CI: 0.55, 0.93), and attained at least secondary education (APR=0.64, CI: 0.46, 0.88) and administration of recommended antibiotic doses (APR = 0.76, CI: 0.59–0.96) posed a lower risk of MDR E. coli carriage. Farms without footbaths posed a heighten risk (APR=1.48, CI: 1.16–1.88). MDR E. coli were highly prevalent on chicken farms. This study underscores the need for antimicrobial stewardship and improved infection prevention strategies on chicken farms.

The article presents the results of the γ-ray and fast neutrons impact on various rice species, in order to obtain mutant forms resistant to salinity (NaCl) and drought factors (sorbite). They are going to be used as initial forms in synthetic selection when creating varieties, adapted to the stressful conditions of, both, soil and climate in the Kazakhstan Aral Sea. The average lethal doses (LD50) of γ-rays and fast neutrons, as well as, the average NaCl and sorbite lethal concentrations were established. A distinct dependence on the effect of ionizing radiation and stress factors on the number of induced resistant mutant forms has been related to the initial rice variety. The largest number of mutant forms was obtained from the local variety Syr Suluy, followed by Leader and Aikerim varieties. Out of all varieties, only 1% of the initially irradiated by γ-rays seeds survived, while after fast neutron irradiation – 4,3%. M1 mutant plants significantly differ from the initial forms in terms of morphological features – plant height, panicle length, and grain size. They are tolerant to lodging, and have short and highly sterile panicles, indicating that they are mutants.

The addition of prebiotics is one of the most important ways to improve the techno-functional properties of bread. In this study, the effects of resistant starch, polydextrose, and inulin on the wheat flour, dough, and bread properties were investigated. In farinography results, resistant starch significantly increased the development time (2:18) with a boosting effect, but polydextrose (1:48) and inulin (1:36) weakened the dough (P &lt;0.05). Inulin, polydextrose, and resistant starch had the most effect on reducing water absorption (40, 43.2, and 48.9) respectively (P &lt;0.05). According to extensography data, inulin had the best result in baking compared to other polysaccharides. In terms of baked breads, samples containing resistant starch had high moisture that could be due to starch gelatinization and moisture-retaining, which delays the staling process of bread. Inulin, polydextrose, and resistant starch prebiotic ingredients affected dough rheological properties and bread quality, and organoleptic characteristics, however, resistant starch was the best.

Background and objective K. pneumoniae appeared to be a significant problem due to its ability to accumulate antibiotic-resistance genes. After 2013, alarming colistin resistance rates among carbapenem-resistant K. pneumoniae have been reported in the Balkans. The study aims to perform an epidemiological, clinical, and genetic analysis of a local outbreak of COLr CR-Kp. Material and methods All carbapenem-resistant and colistin-resistant K. pneumoniae isolates observed among patients in the ICU unit of Military Medical Academy, Sofia from 1 January to 31 October 2023 were included. The results were analyzed according to the EUCAST criteria. All isolates were screened for blaVIM, blaIMP, blaKPC, blaNDM, and blaOXA-48. Genetic similarity was determined using the Dice coefficient as a similarity measure and the unweighted pair group method with arithmetic mean (UPGMA). mgrB genes and plasmid-mediated colistin resistance determinants (mcr-1, mcr-2, mcr-3, mcr-4, mcr-5) were investigated. Results There was a total of 379 MDR-K. pneumoniae isolates, 88% of which were carbapenem-resistant. Of them, there were 9 (2.7%) colistin-resistant isolates in six patients. A time and space cluster for five patients was found. Epidemiology typing showed that two isolates belonged to clone A (pts. 1, 5) and the rest to clone B (pts. 2-4) with 69% similarity. Clone A were coproducers of blaNDM-like and blaOXA-48-like and had mgrB-mediated colistin resistance (40%). Clone B isolates had only blaOXA-48-like and intact mgrB genes. All isolates were negative for mcr-1,-2,-3,-4,-5 genes. Conclusions The study describes a within-hospital spread of two clones of COLr CR-Kp with a 60% mortality rate. Clone A were coproducers of NDM-1 and OXA-48-like enzymes and had mgrB-mediated colistin resistance. Clone B isolates had only OXA-48-like enzymes and intact mgrB genes. No plasmid-mediated was found. The extremely high mortality rate and limited treatment options warrant strict measures to prevent outbreaks.

This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) among non-carbapenemase producing (NCP) and carbapenemase producing (CP) Escherichia coli and Klebsiella pneumoniae. As mutations for ertapenem resistance establish the genetic background for non-carbapenemase meropenem resistance, there is a great need for antibiotic stewards and researchers to understand the determinants of a strain’s propensity to become resistant. Whole genome sequencing was conducted on clinical carbapenem-resistant E. coli (CREC) and K. pneumoniae (CRKP) across 5 hospitals in San Antonio, U.S. from 2012-2018. The majority of carbapenem resistant Enterobacterales (CRE) were NCP (54%; 41/76). The blaCTX-M was found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Antimicrobial susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p &lt; 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p &lt; 0.001). ErMs strains carrying blaCTX-M, had approximately 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem and meropenem susceptible (EsMs) isolates (3.7 v. 0.9, p &lt; 0.001). ErMs also carried more mobile genetic elements (MGEs), particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p &lt; 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. To thwart potential mismanagement of CRE infected patients, future efforts should focus on understanding the mechanism(s) underlying OmpC loss, developing rapid methods to detect blaCTX-M copy number variants, and targeted antimicrobials for NCPE and ErMs strains.

Background: Number of joint infections caused by Vancomycin-resistant pathogens is emerging. Currently no PMMA cement is commercially available to cover VRE. Daptomycin shows promising results in infection treatment, offers a good safety profile and reduced risk for resistance development. Purpose of this in vitro study is to investigate the mechanical stability, handling properties, elution behavior and antimicrobial effectiveness of PMMA cement loaded with three different Daptomycin concentrations in comparison to commercially available ALBC; Methods: Mechanical properties and handling characteristics (ISO 5833, DIN 53435), HPLC elution, antimicrobial effectiveness with proliferation assay (DIN 17025) and inhibition zone testing were investigated; Results: All tested Daptomycin concentrations fulfilled ISO and DIN mechanical strength. Dosage of 0.5. g added Daptomycin did not show any antimicrobial effectiveness in contrast to 1.0 g and1.5 g. Cement with 1.5 g Daptomycin was best in elution and effectiveness, showed good mechanical ISO strength, ISO doughing was a little longer sticky and setting was faster as Vancomycin containing reference cement; Conclusion: PMMA cement containing 0.5 g Gentamicin and 1.5 g Daptomycin could be a good alternative to the already established COPAL® G+V for PJI treatment of VRE.

Although the beneficial health effects of prebiotics have been demonstrated in numerous research papers, its incorporation into daily food remains unfamiliar to consumers. This work evaluates the resistant maltodextrin (RMD) addition in the sensory attributes of pasteurized orange juice, together with the physico-chemical properties and the aromatic profile. RMD addition moderately improved almost all sensory attributes evaluated by panellists. It also proportionally increased °Brix together with density and decreased acidity. Colour changes were registered with higher RMD concentrations. Orange pulp presence affected the volume particle size distribution analysis while RMD addition did not exercised any effect. The aroma volatile compounds were also analysed. Pulp-added samples marked higher alcohol and aldehydes quantity, whereas pulp-free samples registered higher terpenes and terpenoids values. Ketones and acids were also quantified. RMD had a moderate impact on volatile compounds quantifications, playing the orange pulp presence a much more decisive role. A correlation analysis was also performed to relate instrumental and sensorial determinations for all samples. This work proves that the addition of RMD to orange juice is technologically feasible while also achieving a good response at the sensory level.

Type 2 diabetes mellitus (T2DM) has emerged as a major health care concern in modern society, primarily due to lifestyle changes and dietary habits. Obesity-induced insulin resistance is considered as the major pathogenic factor in T2DM. In this study, we have investigated the effect of vindoline, an indole alkaloid of Catharanthus roseus on insulin resistance, oxidative stress and inflammatory responses in high glucose induced insulin resistant L6-myoblast cells, and dexamethasone (IR inducer)/1L-β (inflammation inducer) induced dysfunctional 3T3-L1 adipocytes. Results showed that dexamethasone induced dysfunctional 3T3-L1 adipocytes treated with different concentrations of vindoline significantly enhanced basal glucose consumption, accompanied by increased expression of GLUT-4, IRS-1 and adiponectin. Vindoline treatment significantly suppressed the ROS production and upregulated pro-inflammatory mediators in IL-1β induced dysfunctional adipocytes. Similarly, vindoline treated insulin resistant L6 myoblasts exhibited significantly enhanced glycogen content accompanied with upregulation of IRS-1 and GLUT-4. Thus, in vitro studies of vindoline in insulin resistant skeleton muscle and dysfunctional adipocytes confirmed that vindoline treatment significantly mitigate insulin resistance in myotubes and improves functional status of adipocytes. These results demonstrated that vindoline has the potential to be used as a therapeutic agent to ameliorate obesity-induced T2DM associated insulin resistance profile in adipocytes and skeletal muscles.

Studies have previously described the occurrence of multidrug-resistant (MDR) Escherichia coli in human and veterinary medical settings, livestock, and, to a lesser extent, in the environment and food. While they mostly analyzed foodborne E. coli regarding phenotypic and sometimes genotypic antibiotic resistance and basic phylogenetic classification, we have limited understanding of the in vitro and in vivo virulence characteristics and global phylogenetic contexts of these bacteria. Here, we investigated an E. coli strain (PBIO3502) isolated from a pork sausage in Germany in 2021 in-depth. Whole-genome sequence analysis revealed sequence type (ST)58, which is an emerging international high-risk clonal lineage. In addition to its MDR phenotype that mostly matched the genotype, PBIO3502 demonstrated pronounced virulence features, including in vitro biofilm formation, siderophore secretion, serum resilience, and in vivo mortality in Galleria mellonella larvae. Along with the genomic analysis indicating close phylogenetic relatedness of our strain with publicly available, clinically relevant representatives of the same ST, these results suggest the zoonotic and pathogenic character of PBIO3502 with the potential to cause infection in humans and animals. Also, our study highlights the necessity of the One Health approach while integrating human, animal, and environmental health, as well as the role of meat products and food chains in the putative transmission of MDR pathogens.

The demand for efficient processes through a comprehensive understanding and optimization of welding conditions continues to grow in the manufacturing industry. This study involves heat-resistant 2.25 Cr-1 Mo V-groove steel welding using the square-waveform alternating cur-rent. Experiments were conducted to build the relationship between input variables—such as current, frequency, electrode negativity ratio, and welding speed—and process performance, such as penetration, bay area, deposition rate, melting efficiency, percentage dilution, flux–wire ratio, and heat input. The process was analyzed in light of the defect-free high-deposition weld groove weld, the sensitivity to process parameters, and the optimization and development of the process map. The study proposes an innovative approach to reducing the cost and time of optimizing the one-pass-each-layer V-groove welding process using bead-on-plate welds. Square waveform welding creates a metallurgical notch in the form of a bay at the fusion boundary that can be minimized by selecting appropriate welding conditions. The square waveform submerged arc welding is more sensitive towards changes in current and welding speed than the frequency and electrode negativity ratio; however, the electrode negativity ratio and frequency are minor but helpful parameters to achieve optimal results. The proximity of the planned and experimental results to within 3% confirms the validity of the proposed approach. The investigation shows that 90% of the maximum deposition rate is possible for one-pass-each-layer V-groove welds within heat input and weld width constraints.

Background: Most drug-resistant Escherichia coli isolates in dogs come from diseased dogs. Prior to this study, the prevalence and risk factors of fecal carriage drug-resistant E. coli and epidemic clone sequence type (ST) 131 (including subtypes) isolates in dogs were unknown. Methods: Rectal swabs were used for E. coli isolation from 299 dogs in a veterinary teaching hospital in Taiwan. Antibiotic resistance and multiplex PCR analyses of E. coli for major STs were performed. Result: There were 43.1% cefazolin-resistant, 22.1% fluoroquinolone-resistant, and 9.4% extended-spectrum beta-lactamase-producing E. coli in our cohort. In the phylogenetic study, B2 was the predominant group (30.1%). The cefazolin-resistant group and ciprofloxacin-resistant group had greater antibiotic exposure in the last 14 days (P &lt; 0.05). The age, sex, and dietary habits of the antibiotic-resistant and -susceptible groups were similar. In the seven isolates of ST131 in fecal colonization, the most predominant subtypes were FimH41 and FimH22. Conclusion: Recent antibiotic exposure was related to the fecal carriage of antibiotic-resistant E. coli isolates. Three major subtypes (FimH41, H22, and H30) of ST131 can thus be found in fecal carriage in dogs in Taiwan.

This study aimed to isolate, identify enteric bacterial species from the migratory seagulls migrated to Libyan cost and to assess the antibiotic resistance of these bacteria. A total of 50 fecal samples were collected from slender-billed gulls in January, 2023 at Farwa Island near the city of Zwara. Bacteria were isolated by conventional culturing method, identified by using the Enterosystem 18R, and antibiotic susceptibility testing was conducted on the isolated bacteria. Only 32 of 46 bacteria were identified using biochemical tests. These identified bacteria belong to six species of Enterobacteriacae namely Citrobacter freundii, Pantoea agglomerans, E. coli, Enterobacter cloacae, Serratia liquifaciens, and Proteus mirabilis, with percentages of (17) 53.125%, (10) 31.25%, (2) 6.25%, (1) 3.125%, (1) 3.125%, and (1) 3.125%, respectively. All isolated bacterial species in this study were 100% sensitive to gentamicin and ciprofloxacin. The highest resistance rate was observed against the antibiotic cefoxitin. The results indicated that C. freundii was the most antibiotic-resistant bacterial species isolated in this study. In conclusion, slender-billed gulls carry multi-drug resistant bacteria. The study recommends implementation of a national program to survey antibiotic-resistant bacteria and expanding scientific research on migratory birds.

Neat polyimide films are known to be dense and rigid. They are therefore not suitable for use in membranes, sensors and sustainable energy storage applications. In this study a novel technique has been used to simulta-neously improve the rigidity, damping ability and impact resistance of polyimide membranes. It is demonstrated that dispersion of a small amount of polyaniline copolymer-modified clay of about 0.25-0.5 wt.% into the pol-yimide matrix, resulted in enhanced storage modulus while maintaining high damping ability and glass transition temperature, Tg. Novel polyimide/substituted polyaniline-copolymer-clay nanocomposite membranes containing poly(N-ethyl-aniline-co-aniline-2-sulfonic-acid-modified-clay (SPNEAC) was successfully prepared and in-corporated into polyimide matrix to form modified clay/polyimide nanocomposites. UV-Vis analysis of the nanocomposite films show that the optical transparency of the SPNEAC-PI nanocomposite membranes de-creased with increasing SPNEAC concentration due to the high UV-Vis absorption of SPNEAC. Transmittance of about 3 % was observed in the nanocomposite membrane containing 5wt.% modified clay at 500 nm wave-length, which is significantly lower than that for the neat PI membrane of about 36 %. The dispersion of SPNEAC containing high concentration of clay (≥ 40 wt.% clay), SPNEAC2 in polyimide matrix, resulted in attainment of a higher degree of imidization than was possible for the neat organoclay/polyimide nanocomposite. This behavior is believed to be due to the synergistic interaction between PI and polyaniline copolymer modified clay. The viscoelastic property of polyimide and the nanocomposite membranes was measured by using the dynamic mechanical spectroscopy, DMS. It was shown that the glass transition temperature, Tg of the nano-composites decreased, while the damping ability and impact energy increased with increasing weight fraction of fillers.

(1) Background: Health Care-Associated Infections (HAIs)are a significant public health problem worldwide favoring multidrug-resistant (MDR) microorganisms. The SARS-CoV-2 infection had a negative association with the increase in antimicrobial resistance, and the ESKAPE group had the most significant impact on HAIs. The study aimed to evaluate the bactericidal effect of high concentration O3 gas on some reference and ESKAPE bacteria. (2) Material and Methods: Four standard strains and four clinical or environmental MDR strains were exposed to high ozone doses at different concentrations and times. Bacterial inactivation (growth and cultivability) was investigated using colony counts and resazurin as a metabolic indicator. Scanning electron microscopy (SEM) was performed. (3) Results: The culture exposure to a high level of O3 inhibited the growth of all bacterial strains tested with a statistically significant reduction in colony count compared to the control group. The cell viability of S. aureus (MRSA) (99,6%) and P. aeruginosa (XDR) (29,2%) was reduced considerably, and SEM showed damage on bacteria after O3 treatment (4) Conclusion: High doses of ozone were able to interfere in the growth of all strains studied, evidencing that ozone-based decontamination approaches may represent the future of hospital cleaning methods.

This paper presents the results of the investigation of composite sinters W-TiB2 which were used as an electrode in the process of electro-spark deposition (ESD) and the examination of the deposited layers. The scope of the study includes detailed characteristics of powder mixtures, composite sinters made using the spark plasma sintering method (SPS) and layers deposited in the electro-spark process. The ESD process, using the W+30 vol.% TiB2 electrode, was carried out using an automated device. The substrates were made of copper and aluminium. The topography analysis of the surfaces of the composite layer and the evaluation of their wear resistance properties are also presented. The analysis of the results of research showed the possibility to obtain, using the SPS method, composite materials of good quality, which can be used as electrodes in the ESD process. The obtained layers had increased wear resistance in relation to the substrate material.

The main objective of the present study was to investigate arsenate [As (V)] resistance genes in rice cultivars grown in arsenic contaminated Egyptian soil in order to genetically induce resistance against arsenic in the local rice varieties as well as defining contaminated rice grains and/or soil. Three local rice cultivars; Sakha 102-104 were cultivated on modified Murashige and Skoog Basal Medium (MS medium) containing elevated concentrations of arsenate (0.1, 1 and 10 mg/l). The three varieties showed different resistant attitudes against arsenate with Sakha 104 being the most resistant. Extracted messenger RNA (mRNA) from treated and untreated Sakha 104 plantlets was scanned using differential display to demonstrate the arsenate resistant genes using three different arbitrary primers. About 100 different RNAs with (1500 bp - 50 bp) were obtained from which seven were up-regulated genes, subjected to DNA cloning using TOPO TA system and the selected clones were sequenced. The sequence analysis described four genes out of the seven namely disease resistance protein RPM1, Epstein-Barr virus EBNA-1-like, CwfJ family protein and outer membrane lipoprotein OmlA while the other three genes were hypothetical proteins. It is concluded the four induced genes in the resistant rice cultivar considered as a direct response to arsenic soil pollution. Genes detected in the present study can be used as geno-sensors for rice grains and soil contamination with As (V). Moreover, local rice cultivars may be genetically modified with such genes to induce high resistance and to overcome arsenic soil pollution.

The specialisation and intensification in agriculture have increased the productivity but have also led to the spread of monocultural systems, simplifying production and reducing genetic diversity. The purpose of this study was to propose crop diversification as a tool to increase biodiversity and achieve sustainable and resilient intensive agriculture, particularly in areas with water scarcity. In this paper, a combined Life Cycle Assessment (LCA) and Life Cycle Costing (LCC) was applied to evaluate the environmental and economic sustainability of a differentiated system of cultivation (pomegranate, almond and olive), according to modern intensive and superintensive cropping systems. Based upon the results obtained, it is deduced that pomegranate cultivation generated the highest environmental load, followed by almond and olive. From the financial analysis, it emerged that almond is the most profitable, followed by pomegranate and olive.

The ANFC/ABPE-10 composite film was prepared by ABPE-10 impregnating into ANFC films under negative pressure. And the composite film had meted high performance FOLED substrate requirement even when ANFC dosage was high for approximately 70%, which was consistent with for low cost efficiency, recyclability, and environmentally friendly. The enhanced properties of ANFC films were mainly because of the nature of ABPE-10 itself and the IPN structure formed between ABPE-10 and ANFC film. The transparency of composite films with different ANFC dosage was significantly increased from 67% to 88% by UV-Vis analysis. The composite film inherited the properties of AFNC, obtaining low CTE characteristics and ductile compact structure. The contact angles of ANFC films increased by 102% from 49.2° to 102.9°after dipping ABPE-10. Additionally, the composite films had outstanding mechanical properties such as tensile strength 173.72 MPa, Young’s modulus 4.06 GPa, and elongation at break 5.81%.

Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease due to the absence of effective therapies. A more comprehensive understanding of molecular events, encompassing the dysregulation of microRNAs (miRs) and metabolic reprogramming, holds the potential to unveil precise mechanisms underlying mCRPC. This study aims to assess the expression of selected serum exosomal miRs (miR-15a, miR-16, miR-19a-3p, miR-21, and miR-141a-3p) alongside serum metabolomic profiling and their correlation in patients with mCRPC and benign prostate hyperplasia (BPH). Blood serum samples from mCRPC patients (n=51) and BPH patients (n=48) underwent metabolome analysis through 1H-NMR spectroscopy. The expression levels of serum exosomal miRs in mCRPC and BPH patients were evaluated using quantitative real-time polymerase chain reaction (qRT‒PCR). The 1H-NMR metabolomics analysis revealed significant alterations in lactate, acetate, citrate, 3-hydroxybutyrate, and branched-chain amino acids (BCAAs, including valine, leucine, and isoleucine) in mCRPC patients compared to BPH patients. MiR-15a, miR-16, miR-19a-3p, and miR-21 exhibited a down-regulation of more than twofold in the mCRPC group. Significant correlations were predominantly observed between lactate, citrate, acetate, and miR-15a, miR-16, miR-19a-3p, and miR-21. The importance of integrating metabolome analysis of serum with selected serum exosomal miRs in mCRPC patients has been confirmed, suggesting their potential utility as clinical diagnostic markers.

Staphylococcus pseudintermedius (SP) is an emergent zoonotic agent associated with multidrug resistance (MDR). This work aimed to describe the antibacterial activity of four essential oils (EOs) and silver nanoparticles (AgNPs) against SP. Fifteen SP strains were tested. The four EOs, namely Rosmarinus officinalis (RO), Juniperus communis (GI), Citrus sinensis (AR) and Abies alba (AB), and AgNPs were used alone and in combination to determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) against SP. All strains presented MDR and methicillin resistance. Among the antibiotic cohort, only rifampicin, doxycycline and amikacin were effective. When EOs were tested alone, AB showed the lowest MIC followed by GI, RO and AR (0.23%±0.3; 0.5%±0.51; 0.79%±0.39; 0.93%±0.63). MBC was increased with the following order: AB, GI, AR and RO (3.56%±4.87; 4.93%±6.27; 8.53%±7.2; 10.34%±5.31). MIC and MBC values for AgNPs were 10.74 mg/L±4.23; 261.05 mg/L±172.74. In combination, the MIC and MBC values were lower for all compounds. In conclusion, EOs and AgNPs could be considered as promising antibacterial alternatives to antibiotics.

Ultra-high temperature oxidation-resistant alloys (UTORAs) have received a lot of attention due to the increased research demand for deep space exploration around the world. But UTORAs have the disadvantages of easy oxidation and chalking. So, in this study, a UTORA was prepared by hot-press sintering on VZrHfNbTa (HEA) substrate coated with hafnium. The bonding mechanism, resistance to high-temperature oxidation, and hardness of the sample tests were carried out. The results show that zirconium in the matrix will diffuse into the hafnium coating during the high-temperature sintering process and form the HfZr alloy transition layer, the coating thickness of the composite is about 120 μm, and the diffusion distance of zirconium in the hafnium coating is about 60 μm, this transition layer chemically combines the hafnium coating and the HEA substrate into a monolithic alloy composite. The results of high-temperature oxidation experiments show that the oxidation degree of the hafnium-coated VZrHfNbTa composite material was significantly lower than that of the VZrHfNbTa HEA after oxidation in air at 1600 °C for 5 h. The weight gain of the coated sample after oxidation is 56.56 mg/cm2, which was only 57.7 % compared to the weight gain of the uncoated sample (98.09 mg/cm2 for uncoated), and the surface of the uncoated HEA showed obvious dents, oxidation, and pulverization occurred on the surface and interior of the sample. In contrast, the coated composite alloy sample mainly underwent surface oxidation sintering to form a dense HfO2 protective layer, and the internal oxidation of the hafnium-coated VZrHfNbTa composite alloy was significantly lower than that of the uncoated VZrHfNbTa HEA.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

A plant’s early response to pathogen stress is a vital indicator of its disease resistance. In order to study the response mechanism of resistant and susceptible flax cultivars to Fusarium oxysporum f. sp. lini (Foln), we applied RNA-sequencing to analyze transcriptomes of flax with Foln 0.5, 2 and 8 hours post inoculation (hpi). We found a significant difference in the number of differential expression genes (DEGs) between resistant and susceptible flax clutivars. The number of DEGs in the Fusarium-resistant cultivar increased dramatically at 2 hpi, and a large number of DEGs participated in the Fusarium-susceptible cultivar response to Foln infection 0.5 hpi. GO enrichment analysis determined that the up-regulated DEGs of both flax cultivars were enriched such as oxidoreductase activity and oxidation-reduction process. At the same time, the genes involved in diterpenoid synthesis were up-regulated in resistant cultivar, while those involved in extracellular region, cell wall and organophosphate ester transport were down-regulated in susceptible cultivar. KEGG enrichment analysis showed the genes encoded WRKY 22 and WRKY33 which involved in MAPK signaling pathway were up-regulated expressed in S-29 and down-regulated expressed in R-7, negatively regulated the disease resistance of flax; The genes encoded Hsp 90 family which in involved in plant pathogen interaction pathway were up-regulated in R-7 and down-regulated in S-29, which positively regulated the disease resistance of flax; The genes encoded MYC2 transcription factor and TIFY proteins which involved in plant hormone signaling pathway were up-regulated in R-7, and regulated the jasmonic acid metabolism of flax and the signal transduction of plant hormones. Meanwhile seven regulatory genes with the most correlation were screened out, Among Lus10025000.g and Lus10026447.g regulated other genes expressed both in plant hormone signal transduction pathway and MAPK signal pathway. In conclusion, these findings will facilitate further studies on the function of these candidate genes in flax of response to Fusarium stress, and the breeding of disease-resistant flax cultivar.

Background: In France, no previous studies had addressed the acquisition of multidrug resistant (MDR) bacteria and colistin resistance genes by medical students when undertaking internships abroad. Methods: Nasopharyngeal, rectal, and vaginal swabs samples were collected from 382 French medical students before and after travel to investigate the acquisition of MDR bacteria. The bacterial diversity in the samples was assessed by culture on selective media. We also genetically characterised the isolates of MDR bacteria including Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), methicillin-resistant Staphylococcus aureus (MRSA), and Carbapenemase-producing Enterobacteriacae (CPE) using the real-time polymerase chain reaction method. The samples were collected from 293 students and were investigated for mcr colistin-resistance genes using RT-PCR directly on the samples, followed by conventional PCR and sequencing. Results: A proportion of 29.3% of the participants had acquired ESBL-E and 2.6% had acquired CPE. The most common species and ESBL-E encoding gene were Escherichia coli (98.4%) and bla_CTX-M-A (95.3%), respectively. A proportion of 6.8% of the participants had acquired mcr-1 genes, followed by mcr-3 (0.3%) and mcr-8 (0.3%). We found that taking part in humanitarian missions to orphanages, being in contact with children during travel, the primary destination of travel being Vietnam and north India, using antibiotics during travel, and studying in 2017 were associated with the acquisition of ESBL-E. When the primary destination of travel was Vietnam and the year of study was 2018, this was associated with acquisition of colistin resistance genes. Conclusion: Medical students are at a potential risk of acquiring ESBL-E, CPE and colistin resistance genes. A number of risk factors have been identified, which may be used to develop targeted preventive measures.

Biocides used in antifouling (AF) paints, such as 4,5-dichlorine-2-n-octyl-4-isothiazole-3-one (DCOIT), can gradually leach into the environment. Some AF compounds can persist in the marine environment and cause harmful effects on non-target organisms. Nanoengineered materials, such as mesoporous silica nanocapsules (SiNC) containing AF compounds, have been developed to control their release rate and reduce their toxicity to aquatic organisms. This study aimed to evaluate the acute toxicity of new nanoengineered materials, SiNC-DCOIT and a silver-coated form (SiNC-DCOIT-Ag), as well as the free form of DCOIT and empty nanocapsules (SiNC), on the sun coral Tubastraea coccinea. T. coccinea is an invasive species and can be an alternative test organism for evaluating the risks to native species, as most native corals are currently threatened. The colonies were collected from the Alcatrazes Archipelago, SP, Brazil, and acclimatized to laboratory conditions. They were exposed for 96h to different concentrations of the tested substances: 3.33, 10, 33, and 100 µg L-1 of free DCOIT; 500, 1000, 2000, and 4000 µg L-1 of SiNC; and 74.1, 222.2, 666.7, and 2000 µg L-1 of SiNC-DCOIT and SiNC-DCOIT-Ag. The test chambers consisted of 500 mL flasks containing the test solutions, and the tests were maintained under constant aeration, constant temperature of 23 ± 2°C, and photoperiod of 12h:12h (light/dark). At the end of the experiments, no lethal effect was observed; however, some sublethal effects were noticeable, such as the exposure of the skeleton in most of the concentrations and replicates, except for the controls, and embrittlement at higher concentrations. Adults of T. coccinea were considered little sensitive to the tested substances. This resistance may indicate a greater capacity for proliferation of the species, which is favored in substrates containing antifouling paints, to the detriment of the native species.

Antibiotics have played a crucial role in the reduction of TB incidence globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline of antibiotic development, and different economic and social conditions. In this review, we summarise recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasise that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throught the community.

Prevalence of antimicrobial-resistant bacteria has become a major challenge worldwide. Methicillin-resistant Staphylococcus aureus (MRSA)—a leading cause of infections—forms biofilms on polymeric medical devices and implants, increasing their resistance to antibiotics. Antibiotic administration before biofilm formation is crucial. Raman spectroscopy was used to assess MRSA biofilm development on solid culture media from 0 to 48 h. Biofilm formation was monitored by measuring DNA/RNA-associated Raman peaks and protein/lipid-associated peaks. The search for an antimicrobial agent against MRSA biofilm revealed that Eugenol was a promising candidate as it showed significant potential for breaking down the biofilm. Eugenol was applied at different times to test the optimal time for inhibiting MRSA biofilms, and the Raman spectrum showed that the first 5 h of biofilm formation was the most antibiotic-sensitive time. This study investigated the performance of Raman spectroscopy coupled with Principal Component Analysis (PCA) to identify planktonic bacteria from biofilm conglomerates. Raman analysis, microscopic observation, and quantification of the biofilm growth curve indicated early adhesion from 5 to 10 h of incubation time. Therefore, Raman spectroscopy can help in monitoring biofilm formation on a solid culture medium and performing rapid antibiofilm assessments with new antibiotics during the early stages of the procedure.

The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.

Water-soluble nonionic surfactant, pentaethylene glycol monododecyl ether, C12E5, spontaneously blooms to the surface of spin-cast hydrophobic polyiso-prenes, generating hydrophilic surfaces. This system represents a simple model for hydrophilic chemical modification of rubbery polymers yet demonstrates surprisingly rich, complex and unexpected behaviour. The ver-tical depth profiles were quantified using neutron reflectometry (NR) and deuterated surfactant, and the surface properties were characterized using con-tact angle analysis and atomic force microscopy (AFM). Despite the low surface tension of the toluene solvent used in film preparation and the low surface en-ergy of the PI matrix, NR depth profiles revealed clear evidence of surfactant segregation. This surface layer was typically thicker than a monolayer, but incomplete, yet was remarkably stable with respect to dissolution, even when exposed to hundreds of thousands of times the volume of water required to dissolve all the surfactant on the surface. Despite the apparent resistance to removal from the surface, water exposure does alter the subsequent wettabil-ity of the surface, with a hydrophilic-to-hydrophobic transition occurring after rinsing. Complementary AFM images of these C12E5 / cis-PI films showed unexpected strand-like features on the surface of the film, which we attribute to a non-uniform lateral distribution of some of the surfactant. This surface structure becomes more evident after rinsing, and it appears that there are two distinct populations of surfactant on the PI film surface. We conclude that some of the bloomed surfactant exists as layers, which are relatively inert with respect to rinsing or surface modification, and some is laterally inhomogene-ous. This latter population is primarily responsible for surface wetting be-havior, but is not detected by specular NR.

Bananas, a staple food globally and a key agricultural commodity, face a severe threat from the fungus Fusarium oxysporum form specialis cubense (Foc), significantly impacting production. Genetic improvement to develop resistant cultivars stands out as a crucial strategy to mitigate this disease. This study focused on assessing and recommending enhanced diploid banana varieties for resistance against Foc subtropical race 4 (ST4) and Foc race 1 (R1). Twenty-five improved diploids developed by Embrapa, Brazil, underwent evaluation. Utilizing a scale for internal symptoms at 90 days post-inoculation, genotypes were categorized from highly resistant to highly susceptible based on the internal symptom index. The diploid M53 exhibited high resistance to R1 and resistance to Foc ST4, while only the diploid CNPMF 0534 demonstrated complete resistance to both R1 and ST4, with resistance to the latter likely associated with penetration. These findings provide valuable insights for banana and plantain breeding programs, offering selected diploids for crossbreeding with commercial cultivars to develop new, resistant genotypes against Foc.

Escherichia coli causes several infections like intestinal diarrhea, urinary tract infections, and pneumonia, which are difficult to treat due to the emergence of antimicrobial resistance. The World Health Organisation (WHO) declared carbapenem-resistant E. coli a critical pathogen and called for the development of new antimicrobial agents. Phage therapy, a century-old technique, has been revitalised recently with many successful applications against multi-drug resistant infections. As such, phage therapy is considered one of the most effective alternatives or adjuvants to antibiotics and is also effective in treating multidrug-resistant (MDR) bacterial infections. However, few phages that can kill pathogenic E. coli strains from Southeast Asia have been studied at a molecular level, although the burden of MDR, particularly carbapenem resistance, is high in this region. In this study, three closely related obligately virulent Escherichia phages (øEc_Makalu_001, øEc_Makalu_002, and øEc_Makalu_003) that could infect uropathogenic E. coli were isolated from sewage samples and characterized using morphological as well as sequence-based analysis. Further, a comparative genomic and phylogenetic analysis was done to predict the functional genes and evolutionary relationships. Electron microscopy and genome-based classification revealed that all three phages belonged Krischvirus genus of Straboviridae family. One-step growth curve showed that the latent period of the phages ranged from 15-20 min, the outbreak period was about 50 min, and the burst size ranged between 74-127 PFU/bacterium. Moreover, the phages could tolerate a pH range of 6 to 9 and a temperature range of 25-37°C for up to 180 minutes without significant loss of phage viability. Spotting the purified phages in different clinical isolates showed a broad host-range of isolated Escherichia phages and could lyse up to 30% of the tested pathogenic clinical isolates, including an intra-genus isolate of Klebsiella pneumoniae. The genome organization of all three phages was almost identical and similar to T4-like phage with a full-length genome of ~163 kb. Around 284 coding sequences (CDS) were predicted in each phage, of which only 40% were functional with an average gene length of 951 bp. The coding density in all phages was approximately 95%, while the gene density was 1.73 gene/kbp. Putative lysin, holin, endolysin, and spanin genes were found in the genomes of all three phages, resembling that of T4-like phages implying their phylogenetic relatedness. Furthermore, various in silico sequence analysis tools confirmed that all three phages were strictly virulent with functional lysis modules but devoid of any known virulence or toxin genes, integron-associated genes and antimicrobial-resistance (AMR) genes. In summary, pre-clinical experimental analysis and exploration of genomic features suggest that all three phages may be suitable candidates for therapeutic applications against uropathogenic E. coli.

Multidrug-resistant tuberculosis emerged as a serious challenge to tuberculosis management and control. In the Eastern Cape, the Beijing variants are prevalent and a driving force of multidrug-resistant tuberculosis; hence, we investigated the distribution of gene mutations in Beijing strains compared to non-Beijing strains. Multidrug-resistant tuberculosis and heteroresistant isolates were identified in 412 sputum cultures by drug susceptibility testing. The isolates were analyzed for mutations in three genes associated with resistance to antituberculosis first-line drugs: katG and inhA promoters for isoniazid and rpoB for rifampicin. All isolates were genotyped by spoligotyping. There were more males than females and a more economically active age group in the study. The most prevalent mutations in rpoB resistance were in S531L, katG in S315Tb, and inhA in c-15tb. Heteroresistance was found in 18 isolates. Beijing variants were predominant. Most of the heteroresistant isolates were INH, with heteroresistance occurring more in the inhA gene mutation region c-15tb. Beijing and LAM variants were found more frequently in INH heteroresistant isolates. Mutations in katG S315Tb and rpoB S531L were higher in Beijing variants. The Beijing family is a major contributor to the epidemiological picture and accounts for most of the multidrug-resistant tuberculosis in the study area.

Equine metabolic syndrome (EMS) is a major health threat in veterinary endocrinology medicine worldwide, and there is growing interest in utilizing molecular agents for modulation of hepatocyte function for potential clinical applications with recent studies showing promising results in the inhibition of PTP1B on adipose-derived stromal cells. In this study, we investigated the effects of MSI-1436 on equine hepatic progenitor cells (HPCs) in terms of their proliferative activity, glucose uptake, and mitochondrial morphogenesis under lipotoxic condition. Our study found that MSI-1436 promotes the entry of HPCs in the cell cycle and rescues them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the morphological architecture of the cells. Additionally, our findings suggest that MSI-1436 enhances the 2-NBDG internalization by increasing the expression of SIRT1, which is associated with liver insulin sensitivity, and promotes mitochondrial dynamics by modulating their number and morphotype through PINK1, MFN1, and MFN2 increased expression. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in the treatment of EMS and insulin dysregulation.

The incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing considerably annually since being first reported in 2008. Gyeonggi Province has the largest number of healthcare facilities in South Korea, which contribute to its regional vulnerability to CRE infections. Thus, there is a need to obtain up to date information on the occurrence of CRE infections in the Gyeonggi Province to take corrective measures. Therefore, in this study, we aimed to investigate the overall trends of CRE occurrence in Gyeonggi Province over the past 4 years and the epidemiological characteristics of CRE-related mortality. Patients admitted to a healthcare facility in Gyeonggi Province from January 2018 to December 2021 with positive blood cultures to CRE were included in the study and investigated. Additionally, the risk factors for CRE-related death were determined using data from CRE-positive patients who died within 30 days of last blood sampling. Older adults aged 70 and over accounted for the highest percentage of both survivors and non-survivors with CRE bacteremia. The number of non-survivors was higher in tertiary hospitals and among patients in intensive care unit. There were no significant differences in the mortality risk according to the use of antibiotics. Moreover, non-survivors were predominant among patients with hypertension, malignant tumor, and those having two or more underlying diseases. Klebsiella pneumoniae was the most common CRE strain in both survivors and non-survivors. Among the survivors, carbapenemase-producing Enterobacteriaceae was detected in 151 cases (71.2%) and 49 cases (23.1%) in the KPC and NDM groups, respectively. Among the non-survivors, it was detected in 25 cases (86.2%) and 5 cases (17.2%) in the KPC and NDM groups, respectively. The endemicity of CRE in South Korea has been proposed for several years; our results have suggested endemicity of CRE in the Gyeonggi Province. Despite the strengthened infection control policies in healthcare facilities during the pandemic, there has been an increasing trend in the isolation of CRE strains in South Korean long-term care hospitals and hospitals within Gyeonggi Province. Factors such as history of hospitalization and underlying diseases have been identified as risk factors for CRE-related deaths. However, to address this issue strictly, it is important to establish infection control infrastructure tailored based on each type of healthcare facility, and elaborate specific government support measures, accordingly.

Klebsiella pneumoniae (Kp) has gained prominence in the last two decades due to its global spread as a multi-drug resistant (MDR) pathogen. Further, Carbapenem-Resistant Kp are emerging at an alarming rate. The objective of this study was (1) to evaluate the prevalence of β-lactamases, especially carbapenemases in Kp isolates from India, (2) determine the most prevalent sequence type (ST) & plasmids, and their association with β-lactamases. Clinical samples of K. pneumoniae (n=65) were collected from various pathology lab, drug susceptibility and minimum inhibitory concentrations (MIC) were detected. Whole genome sequencing (WGS) was done for (n=22) resistant isolates and WGS analysis was performed using various bioinformatics tools. Additional Indian MDR Kp genomes (n=187) were retrieved using Pathosystems Resource Integration Center (PATRIC) database. Detection of β-lactamase genes, location, plasmid replicons, and ST type of genomes were carried out using CARD, mlplasmids, PlasmidFinder, and PubMLST respectively. All data were analyzed and summarized using iTOL tool. ST231 was highest, followed by ST147, ST2096 & ST14 among Indian isolates. blaAmpH was detected as the most prevalent gene followed by blaCTX-M-15, blaTEM-1. Among carbapenemase genes, blaOXA-232 was prevalent and associated with ST231, ST2096 and ST14, which was followed by blaNDM-5 which was observed to prevalent in ST147, ST395 &ST437. ST231 genomes were most commonly found to carry Col440I and ColKP3 plasmids. ST16 carried mainly ColKP3, and Col (BS512) was abundantly present in ST147 genomes. One Kp isolate with novel MLST profile was identified, which carried blaCTX-M-15, blaOXA-1 and blaTEM-1. ST16 &ST14 from this study, which is mostly dual producer of carbapenem and ESBL genes, could be emerging high-risk clones in India.

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, 68Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of 68Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: 68Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those 2/17 had NePC. Semiquantitative analysis with standardized uptake values (SUV) (e.g. SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. 68Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastic lesion with identifiable 68Ga-DOTATATE uptake. Marked 68Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. 3 patients had mild 68Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after 68Ga-DOTATATE imaging. Conclusions: 68Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with 68Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.

Drought events are predicted to become more prevalent in the future. Evaluating the performance of herbicide-resistant and susceptible weed ecotypes to progressive drought can provide insights into whether resistance trait(s) increased or reduced the fitness of a resistant population. Two experiments were conducted in the greenhouse between January and May 2021 to evaluate drought tolerance differences between Palmer amaranth accessions resistant to S-metolachlor or glyphosate and their susceptible counterparts. The accessions used were: S-metolachlor-resistant (17TUN-A), a susceptible standard (09CRW-A), and glyphosate-resistant (22 to 165 EPSPS copies) and glyphosate-susceptible (3 to 10 EPSPS copies) plants from accession 16CRW-D. Daily transpiration of each plant was measured. The daily transpiration rate was converted to normalized transpiration ratio (NTR) using a double-normalization procedure. The daily soil water content was expressed as a fraction of transpirable soil water (FTSW). The threshold FTSW (FTSWcr), after which NTR decreases linearly, was estimated using a two-segment linear regression analysis. The data showed differences between S-metolachlor- resistant and -susceptible accessions (P ≤ 0.05). The FTSW remaining in the soil at the breakpoint for the S-metolachlor-susceptible accession (09CRW-A) was 0.17±0.007. The FTSW remaining in the soil at the breakpoint for the S-metolachlor-resistant accession (17TUN-A) was 0.23±0.004. Although the mechanism endowing resistance to S-metolachlor might have contributed to increased drought tolerance, follow-up experiments are needed to verify this finding. Increased EPSPS copy number did not improve drought tolerance of Palmer amaranth.

Transparent materials used for facial protection equipment provide protection against microbial infections caused by viruses and bacteria, including multidrug-resistant strains. However, transparent materials used for this type of application are made of materials that do not possess antimicrobial activity. They just avoid direct contact between the person and the biological agent. Therefore, healthy people can get infected through contact of the contaminated material surfaces and this equipment constitute an increasing source of infectious biological waste. Furthermore, infected people can transmit microbial infections easily because the protective equipment do not inactivate the microbial load generated while breathing, sneezing, or coughing. In this regard, the goal of this work consisted of fabricating a transparent face shield with intrinsic antimicrobial activity that could provide extra-protection against infectious agents and reduce the generation of infectious waste. Thus, a single-use transparent antimicrobial face shield composed of polyethylene terephthalate and an antimicrobial coating of benzalkonium chloride has been developed for the next generation of facial protective equipment. The antimicrobial coating was analyzed by atomic force microscopy and field emission scanning electron microscopy with elemental analysis. This is the first facial transparent protective material capable of inactivating enveloped viruses such as SARS-CoV-2 in less than one minute of contact, and the methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis. Bacterial infections contribute to severe pneumonia associated with the SARS-CoV-2 infection, and their resistance to antibiotics is increasing. Our extra protective broad-spectrum antimicrobial composite material could also be applied for the fabrication of other facial protective tools such as such as goggles, helmets, plastic masks and space separation screens used for counters or vehicles. This low-cost technology would be very useful to combat the current COVID-19 pandemic and protect health care workers from multidrug-resistant infections in developed and underdeveloped countries.

Infections by methicillin-resistant Staphylococcus aureus (MRSA) are continuously expanding within the community. Chicken meat is usually contaminated by MRSA, and this contaminated chicken meat is an important source of foodborne infections in humans. In this study, a cross-sectional supershop survey was conducted to determine the prevalence and antimicrobial resistance pattern of MRSA in 113 domestic frozen chicken meat samples purchased from nine branded supershops available in five divisional megacities of Bangladesh. The study also focused on the determination of methicillin resistance gene in MRSA isolates. S. aureus was identified by standard culture-based and molecular methods, and subjected to antimicrobial susceptibility testing. MRSA was screened by cefoxitin disk diffusion test. Methicillin resistance gene was identified by PCR. Of samples, 54.9% were positive for S. aureus, and, of these, 37.1% isolates were identified as MRSA. All the isolates were multidrug resistant (MDR): 52.2% were resistant to 6−8 antimicrobial classes, and 47.8% isolates to 9−12 classes. Three (3.2%) isolates of S. aureus were possible extensively drug resistant. The highest rates of resistance were observed against cefoxitin (100%), followed by nalidixic acid, ampicillin and oxacillin (97.7%), colistin (91.3%), amoxicillin-clavulanic acid and amoxicillin (87%), penicillin-G and cloxacillin (82.6%), oxytetracycline (78.3%) and cefixime (73.9%). Screening of methicillin resistance gene revealed that 43.5% isolates of MRSA were positive for mecA gene. The high prevalence of MDR MRSA in frozen chicken meat samples in this study emphasizes the need for better sanitary education of food handlers in hygienic practices focusing on their potential role as reservoirs and spreaders of MRSA.

Lytic bacteriophages have the efficacy to act and eradicate pathogenic bacteria as an attractive tool in the near future. Bacteriophages specifically kill multidrug-resistant bacteria even which have the capacity to form biofilms. The present review mainly focused on the efficacy of bacteriophages and cocktails as therapeutic agents against predominate MDR-bacteria and their biofilms which are isolated from septic wound infections. The body of evidence includes data from studies investigating bacteriophages from sewage samples as novel antibacterial and antibiofilm agents against pathogenic bacteria. The goal of this review is to present an overview on predominant bacteria from septic wound infection, the biofilm-forming capacity of bacteria, lytic effect of bacteriophages and phage cocktails with an emphasis on the application of bacteriophages against septic wound causing bacteria.

In this work, nylon 6/ P(N-phenylmaleimide-alt-styrene) blends were prepared by melt blending, and the mechanical, heat-resistant, crystallographic and dynamical mechanical properties of nylon 6/ P(N-phenylmaleimide-alt-styrene) blends with different contents were investigated and analyzed. The results showed that the mechanical properties decreased with increasing PNS, while the heat deflection temperature (HDT), relative crystallinity (Xn), and storage modulus (G’) increased with increasing PNS. The results of differential Scanning Calorimetry (DSC) proved the PNS played the positive role of nucleating PA6. And the results of dynamic mechanical analysis (DMA) proved the PNS could improve the rigidity of PA6/PNS blends. From the SEM, these PNS domains were between 0.2 and 4 μm in diameter. The experimental results indicated that the addition of PNS improved the rigidity of PA6/PNS blends, and then improved the heat-resistant property.

Rice blast and brown planthopper (BPH) are two of the most destructive diseases and pests in rice (Oryza sativa L.) production in China. The development of multi-resistant varieties is widely recognized as the most efficient and environmentally friendly approach to controlling crop diseases and pests. Functional molecular markers (FMMs) have been developed from functional variants in the genic region associated with trait variation, greatly enhancing the efficiency of identifying and pyramiding valuable genes in crop breeding. In this study, two FMMs and a multiplex PCR amplification system were developed for two major broad-spectrum BPH resistance genes, Bph6 and Bph9. By assistance of FMMs in multi-resistant rice restorer line development pipeline, two lines (Huahui7713 and Huahui3006) with blast and BPH resistance were developed by pyramiding three resistance genes Pigm, Bph6 and Bph9. Huahui7713 and Huahui3006 as male lines, two new hybrid rice varieties (WeiLiangYou7713 and Xuanliangyou3006) were certificated and commercial released in China. WeiLiangYou7713 and Xuanliangyou3006 showed improved blast and BPH resistance, and no penalty on yield and grain-quality. Annual promotion area of WeiLiangYou7713 has exceeded 53.3 thousand hectares, indicating its widespread adoption and success in the market. Huahui7713 and Huahui3006 could have great potential for utilization in blast and BPH resistance rice breeding.

The outbreak of yellow fever transmitted by Aedes aegypti has been of major concern in Nigeria, this mosquito also transmits several other arboviruses globally. The control of many of the Aedes aegypti borne diseases relies heavily on the use of insecticides. Therefore, constant monitoring of insecticide resistance status and associated mechanisms in crucial within the local population. Here, we determined the resistance profile of adult Aedes aegypti from Ikorodu Local Government Area of Lagos State, Nigeria to different classes of insecticides using WHO procedures. The presence of kdr mutations F1534C, S989P and V1016G were also determined among resistant populations using molecular methods. High level of resistance to DDT and pyrethroid was rec-orded in Aedes aegypti in this study, though possible resistance to deltamethrin was reported in one of the locations. Resistance to bendiocarb was recorded in Majidun community while Aedes aegypti in both locations were susceptible to malathion. The presence of F1534C mutation associated with resistance in Aedes aegypti was detected for the first time in Nigeria, and the presence of S989P mutation was detected singly and in co-occurrence with F1534C for the first time in Africa. The role of these mutations in resistance phenotype expressed in Aedes aegypti in this study area need to established.

1) Background: carbapenem-resistant Acinetobacter baumannii (CRAB) is an opportunistic Gram-negative pathogen that has a significant role in healthcare-associated infections. Unlike several studies on the antibiotic-resistant epidemiology of A. baumanni, virulence molecular epidemiology was less studied. This study aimed to investigate CRAB virulence genes and their ability to form biofilms, and to correlate their biofilm formation ability with both; biofilm-encoding virulence genes and carbapenemase-encoding resistance genes. 2) Methods: 107 CRAB clinical isolates were collected from two hospitals in Jordan between 2018 and 2019 and were screened for virulence genes using PCR. In addition, biofilm formation ability was assessed using the microtiter plate method. 3) Results: the frequencies of the bap, OmpA, surA, PLD, paaE, basD, and traT virulence genes were 99.10%, 98.20%, 98.20%, 95.50%, 89.10%, 86.40%, and 8.20%, respectively. Overall, 86.4% of the tested isolates were biofilm formers with varying degrees; weak (28.2%), moderate (36.4%) and strong (21.8%). A significant relationship was found between the carbapenemase-encoding gene (OXA-23 gene) and biofilm production. 4) Conclusion: to the best of our knowledge, this is the first study in Jordan that inspected CRAB virulence genes and highlighted the importance of improving infection control measures to avoid CRAB outbreaks.

In recent years, humanity has faced a growing challenge posed by the rise of antibiotic-resistant bacteria, resulting in an alarming surge in fatalities and the emergence of increasingly hard-to-manage diseases. Among these resilient pathogens is Acinetobacter baumannii, due to its escalating prevalence in hospitals, elevated mortality rates, and resistance to treatment. Despite its clinical significance, our understanding of this pathogen in non-hospital settings and its virulence factors remains limited. Therefore, this review aims to shed light on the latest research regarding its ecological niche, microbiological traits, and antibiotic resistance profiles. Recent investigations have expanded its detection to various environmental niches, including rivers, treatment plants, and soils. Moreover, this bacterium has been discovered in diverse food sources such as meat and vegetables, as well as in farm animals and household pets like dogs and cats. This broader presence of Acinetobacter baumannii outside of hospital environments underscores a significant risk of environmental contamination, necessitating heightened awareness and preventive measures to address potential public health implications.

As the control brain of the petrochemical plant, blast resistant performance requirements of the petrochemical control room should be guaranteed when the vapor cloud explosion occurs in the petrochemical production process. 3D-Kagome truss core sandwich structure is a kind of blast resistant material with high energy absorption. Considering the influence factors of the radius of the truss core rod and thickness of the upper and lower panels, in this paper, blast resistant performance of a real steel petrochemical control room with 3D-Kagome truss core sandwich wall is analyzed. With the optimization goal of plastic deformation energy and panel displacement, the optimal wall thickness and radius of the truss core rode are obtained. The optimized blast resistant wall is assembled, and the dynamic response of the steel petrochemical control room with the 3D-Kagome truss core sandwich blast resistant wall is analyzed. The simulation results show that the truss core layer does not dissipate the blast energy effectively when the radius ratio of the truss core rod is larger than 2.7% of the total thickness of the wall; with the increase of the thickness of the upper and lower panels, the proportion of plastic deformation energy of the truss core layer increases gradually and then tends to be a stable proportion value, that is about 90%; When the thickness ratio of the panel is 6.7% of the total one of the wall and the radius ratio of the truss core rod is 2.7% of the total thickness of the wall, the optimal blast resistant 3D-Kagome sandwich wall is determined.

The methyltransferase, KMT5A has been proposed as an oncogene in prostate cancer and therefore represents a putative therapeutic target. To confirm this hypothesis we have performed a microarray study in a prostate cancer cell line model of androgen independence following KMT5A knockdown in the presence of transcriptionally active androgen receptor (AR) to understand which genes and cellular processes are regulated by KMT5A in the presence of an active AR. We observed that 301 genes were down-regulated whilst 408 were up-regulated when KMT5A expression was reduced. KEGG pathway and Gene Ontology analysis revealed apoptosis and DNA damage signaling are up-regulated in response to KMT5A knockdown whilst protein folding and RNA splicing were down-regulated. Under these conditions, the top non-AR regulated gene was found to be CDC20, a key regulator of the spindle assembly checkpoint with an oncogenic role in several cancer types. Further investigation revealed that KMT5A regulates CDC20 in a methyltransferase dependent manner to modulate both histone H4K20 methylation within its promoter region and indirectly via the p53 signalling pathway. A positive correlation between KMT5A and CDC20 expression was also observed in clinical prostate cancer samples further supporting this association. Therefore, we conclude that KMT5A is a valid therapeutic target for the treatment of prostate cancer and CDC20 could potentially be utilized as a biomarker for effective therapeutic targeting.

The recent approval of 177Lu PSMA-617 (Pluvicto®) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. 177Lu PSMA-617, along with the bone specific radiotherapeutic agent, 223RaCl2, are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA) -, gastrin-releasing peptide receptor (GRPR) -, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies.

We previously described a model of deep intrinsic resistance of breast cancer wherein we used a function-based approach to selection of cancer cells that can survive a variety of challenges in prolonged but reversible quiescence. Our experimental results suggested that resistant cancer cells possess a variety of mechanisms, including modifications of the epigenome and transcriptome, for generating a high degree of cellular heterogeneity. In the present study, we evaluated JIB-04, a small-molecule epigenetic inhibitor initially discovered to inhibit cancer growth, to determine its ability to affect deep intrinsic resistance in our breast cancer model. We found that long pretreatment with JIB-04 sensitized resistant triple-negative inflammatory breast cancer cells and their parental cell line SUM149 to the chemotherapeutic drugs doxorubicin and paclitaxel. Resistant cancer cells derived from another inflammatory breast cancer cell line, FC-IBC02, were considerably more sensitive to JIB-04 than was the parental cell line. Investigating a mechanism of sensitization, we found that JIB-04 exposure increased the expression of PD-L1 in resistant cells, suggesting that JIB-04 may also sensitize resistant breast cancer cells to anti-PD-L1 immune therapy. Finally, these results support the usefulness of our experimental strategy for evaluating anticancer agents such as JIB-04 that may halt cancer evolution and prevent development of cancer resistance to currently used therapies.

Critical care of neonates involves substantial usage of antibiotics and exposure to multidrug resistant (MDR) nosocomial pathogens. These pathogens are often exposed to sub-MIC doses of antibiotics which might result in a range of physiological effects. Therefore, to understand the outcome of sub-inhibitory dosage of antibiotics on Staphylococcus populations, nasal swab specimens were collected from 34 neonates admitted to the Sick Newborn Care Unit between 2017-2018, a total of 41 non-repetitive isolates were included in this study. Staphylococcus haemolyticus was the prevalent species (58.54%) with high non-susceptibility to cefotaxime (CTX) (79.16%), gentamicin (87.50%), and meropenem (54.17%). Biofilm forming abilities of S. haemolyticus isolates in the presence of sub-optimal CTX (30μg/mL), the predominantly prescribed β-lactam antibiotic, were then determined by crystal violet assays and extracellular DNA (eDNA) quantitation. CTX was found to significantly enhance biofilm production among the non-susceptible isolates (p-valueWilcoxin test- 0.000008) with increase in eDNA levels (p-valueWilcoxin test- 0.000004). Additionally, no changes in non-susceptibility were observed among populations of two MDR isolates, JNM56C1 and JNM60C2 after >500 generations of growth in the absence of antibiotic selection in vitro. These findings demonstrate that sub-MIC concentration of CTX induces biofilm formation and short-term non-exposure to antibiotics does not alter non-susceptibility among S. haemolyticus isolates.