The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Superficial mycoses, encompassing a range of fungal infections affecting the outer layers of the skin, hair, and nails, have become increasingly prevalent in recent years. While these infections are generally non-life-threatening, the emergence of antifungal resistance poses a growing threat to effective treatment strategies. In this article we explore the escalating specter of antifungal resistance in superficial mycoses, focusing on the underlying mechanisms driving resistance, the clinical implications, and potential avenues for mitigation. The rise of antifungal resistance in superficial mycoses is multifactorial. Consequently, the efficacy of conventional treatments is diminishing, leading to persistent or recurrent infections. Understanding the molecular mechanisms underlying antifungal resistance is crucial for developing targeted therapeutic approaches. Research efforts aimed at unraveling these mechanisms are essential for identifying new drug targets and designing innovative treatment strategies to combat resistant strains. In response to the escalating threat of antifungal resistance, a multifaceted approach is required. This includes enhanced surveillance of antifungal susceptibility patterns, the development of novel antifungal agents, and the implementation of stringent guidelines for antifungal use. Additionally, educational initiatives targeting healthcare professionals and the public are essential to promote responsible antifungal use, reduce the risk of resistance emergence, and improve treatment outcomes.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies de-scribing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonautes proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases and an atypical ribonuclease III (RNaseIII). NCRIP regulates the expression of mRNAs by degrading them in a specific manner. Its mechanism binds dsRNA but only cuts ssRNA. NCRIP exhibits a diversity of functional roles. It represses the epimutational pathway and the lack of NCRIP increases the generation of drug resistant strains. NCRIP also regulates the control of retrotransposons expression, playing an essential role in genome stability. Finally, NCRIP regulates the response during phagocytosis, affecting the multifactorial process of virulence. These critical NCRIP roles in virulence and antifungal drug resistance, along with its exclusive presence in Mucorales, mark this pathway as a promising target to fight against mucormycosis.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

This paper illustrates an experimental activity for the closed-loop position control of an actuator made using shape memory alloy (SMA) wire. A solution with the self-sensing effect was implemented to miniaturize the systems, i.e., without external sensors. A proportional control algorithm was initially used, demonstrating the idea's feasibility: the wire can behave simultaneously as an actuator and sensor. An experimental investigation was subsequently conducted for the optimization of the developed actuator. As for the material, a Flexinol wire, Ni-Ti alloy, with a diameter of 0.150 mm and a length of 200 mm, was used. Preliminarily, a characterization of the SMA wire at constant and variable loads was carried out: the characteristics detected are elongation vs. electric current and elongation vs. electrical resistance. The control system is PC-based with a data acquisition card (DAQ). A drive board has been designed and built to read the wire's electrical resistance and power it by pulse width modulation (PWM). A notable result is that the actuator works with good precision and in dynamic conditions, even when it is called to support a load up to 65% different from that for which the electrical resistance-length correlation has previously been experimentally obtained, on which the control is based. This opens up the possibility of using the actuator in a counteracting configuration with a spring, which makes hardware implementation and control management simple.

Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations in dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies, and 31 articles referring to case reports/clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts/essential oils, calcineurin inhibitors, peptides, disinfectant agents and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e.: azole [mainly itraconazole], terbinafine or griseofulvin) plus a topical medication (i.e.: azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful in accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available as far, it is desirable to continue the research in this field.

In agriculture, soil-borne fungal pathogens, especially Fusarium oxysporum strains, are posing a serious threat to efforts to achieve global food security. In the search for safer agrochemicals, silica nanoparticles (SiO2NPs) have recently been proposed as a new tool to alleviate pathogen damage including Fusarium wilt. Hollow mesoporous silica nanoparticles (HMSNs), a unique class of SiO2NPs, have been widely accepted as a desired pesticide carrier. However, their role in enhancing the disease resistance and the specific mechanism remain unknown. In this study, three sizes of HMSNs (19, 96 and 406 nm as HMSNs–19, HMSNs–96 and HMSNs–406, respectively) were synthesized and characterized to determine their effects on seed germination, seedling growth, and Fusarium oxysporum f. sp. phaseolus (FOP) suppression in cowpea roots by foliar spray using phenotypes, fresh biomass and disease progression as indicators. The results revealed that three HMSNs exhibited no adverse impacts on seed germination and tended to improve plant growth. Also, they exert their FOP suppression with a size- and concentration-dependent manner. HMSNs–406 possessed the best control effect at a concentration of 1000 mg/L showing an upto 40.00% decline in the disease severity. The Si(OH)4 control was also effective on FOP suppression at a lower concentration of 100 mg/L, whereas its higher concentrations exhibited obviously adverse impacts on FOP control, seed germination and plant growth. Moreover, we conformed that HMSNs posed their Fusarium wilt suppression in cowpea plant by activating SA (salicylic acid)-dependent SAR (systemic acquired resistance) responses rather than directly suppressing FOP. A higher level of SA content and elevated expression of its maker genes of PR-1 and PR-5 in HMSNs–406 treated cowpea roots provided substantial evidences of this mode of action. Other resistance-related genes, as well as defense-responsive enzymes, were also involved in the HMSNs-activated SAR pathway. Overall, for the first time, our results extended a new role of HMSNs as a potent elicitor to serve as a versatile alternative for plant disease protection of low cost, highly efficiency and sustainability.

Continuous technological progress places significant demands on the materials used in increasingly modern devices. An important parameter is often the long-term thermal resistance of the material. The use of heat-resistant polymer materials worked well in technologically advanced products. An economically justified direction in searching for new materials is the area of polymer nanocomposite materials. It is necessary to appropriately select both the polymer matrix and the nanofillers best able to demonstrate the synergistic effect. A promising area of exploration for such nanocomposites is the use of organosilicon polymers, which results from the unique properties of these polymers related to their structure. This review presents the results of the analysis of the most important literature reports regarding organosilicon polymer nanocomposites with increased thermal resistance. Particular attention was paid to modification methods of silicone nanocomposites focused on the increase of their thermal resistance related to the modification of siloxane molecular structure and by making nanocomposites using inorganic additives, carbon nanomaterials. Attention was also paid to such important issues as the influence of the dispersion of additives in the polymer matrix on the thermal resistance of silicone nanocomposites and the possibility of modifying the polymer matrix and permanently introducing nanofillers thanks to the presence of various reactive groups. The thermal stability mechanism of these nanocomposites was also analysed.

Culex quinquefasciatus is an important target for vector control because of its ability to transmit pathogens that cause disease. Most populations are resistant to pyrethroids and often to organophosphates, the two most common classes of active ingredients used by public health agencies. A knockdown resistance (kdr) mutation, resulting in a change from a leucine to phenylalanine in the voltage gated sodium channel, is one mechanism contributing to the pyrethroid resistant phenotype. Enzymatic resistance has also been shown to play a very important role. Recent studies have shown strong resistance in populations even when kdr is relatively low which indicates factors other than kdr may be larger contributors to resistance. In this study, we examined on a statewide scale (over 70 populations), the strength of the correlation between resistance in the CDC bottle bioassay and the kdr genotypes and allele frequencies. Spearman correlation analysis showed only moderate (-0.51) and weak (-0.29) correlation between the kdr genotype and permethrin and deltamethrin respectively. The frequency of the kdr allele was an even weaker correlate. These results indicate, in contrast to Aedes aegypti, assessing kdr in populations of Culex quinquefasciatus is not a good surrogate for phenotypic resistance testing.

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

The aim of our work was to check if one of the products of natural origin, namely honey bee propolis may be an alternative or supplement to currently used antifungal agents. The activity of 50 ethanolic extracts of propolis (EEPs), harvested in Polish apiaries, was tested on a group of 69 clinical isolates of C. albicans. Most of the EEPs showed satisfactory activity, with minimum fungicidal concentrations (MFC) mainly in the range of 0.08-1.25% (v/v). Eradication of biofilm from polystyrene microtitration plates in 50% (MBEC50) required concentrations in the range of 0.04% (v/v) to more than 1.25% (v/v). High activity was also observed in eradication of biofilm formed by C. glabrata and C. krusei on the surfaces of PVC and silicone catheters. EEPs at subinhibitory concentrations inhibited yeast-to-mycelia morphological transformation of C. albicans in liquid medium and mycelial growth on solid medium. A synergistic effect was observed for the action of EEPs in combination with fluconazole (FLU) and voriconazole (VOR) against C. albicans. In the presence of EEP at concentration as low as 0.02%, the MICs of FLU and VOR were 256 to 32 times lower in comparison to those of the drug alone. Evidences for the fungal cell membrane as the most probable target of EEPs are presented.

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have an elevated resistance to exogenous antimicrobial peptides (AMPs) – both, with regard to peptide bulk concentration in the medium, and the numbers of peptide molecules per cell. By monitoring integration of the AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy-coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.

Carbapenem antibiotics are the drug of choice for treating multidrug-resistant bacterial infections. Metallo-beta-lactamases (MBLs) are carbapenemase capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, a need to assess the frequency and phenotypic resistance phenomena of two MBL genes in diarrheal and urinary tract infections (UTIs). Samples were collected through a cross-sectional study, with MBLs genes detected via PCR. Two hundred twenty eight diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively.  Total 142 UTI pathogens were obtained from 150 urine samples, with Klebsiella spp. (39%) and Escherichia coli (24%) are the major pathogens. Phenotypic resistance to amoxycillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively.  Twenty four diarrheal isolates carried either blaNDM-1 or blaVIM genes; the overall MBL gene prevalence was 10.5%. Thirty six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes.  MBL genes exhibited a strong association with phenotypic carbapenem and other beta-lactam antibiotic resistance. Resistance to carbapenems requires active surveillance and stewardship.

Cadmium Sulfide nanoparticle (CdS-LA hybrid nanoparticles) was synthesized here by a green approach using the precursor cadmium acetate and sodium sulphide along with the extract of a plant Lathyrus aphaca L. containing the phytochemicals which were responsible for surface modification of nanoparticles. The nanoparticle was used to evaluate their inhibition potential against species of bacteria and fungi. The nanoparticles were characterized by XRD which demonstrates the hexagonal crystal structure. SEM confirms the homogenous surface appearance of the CdS-LA hybrid crystalline structure. EDX analysis confirms surface modification of nanoparticles by phytochemicals. FTIR confirmed the Cd-S linkage laterally with the related functional groups and the presence of metabolites on the surface of nanoparticles. The UV-visible spectroscopy confirmed the peak at the characteristic wavelength range but a slight shift occurred in the peak of the CdS nanoparticles due to the presence of the phytochemicals. This study particularly provides an environment-friendly strategy to synthesize the CdS nanoparticles capped by Lathyrus Aphaca L. extract that are biologically active due to the mediation of the plant extract. CdS-LA hybrid nanoparticles have shown inhibition potential against various species of bacteria and fungi and realize the biological importance of the green synthesis of nanoparticles especially mediated with the plant extract.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

This study explored the effects of cryogenic treatment on the microstructure, hardness, and wear-resistance of diamond-like carbon (DLC) by cryogenically treating NAK 80 mold steel coated with DLC. Raman spectroscopy analyzed the structure of the DLC film. Nanoindenter analyzed the hardness and Young’s modulus of the film, and their relationship determined the wear resistance. Wear test assessed the wear rate and friction coefficient of the DLC film. The results showed that cryogenic treatment increased the rate of carbide precipitation and refined the grain structure. Raman spectroscopy indicated that the Raman intensity rate (I_D/I_G) of treated DLC films was smaller than those without cryogenic treatment. When the sp3 bond increased, the hardness and wear-resistance of the DLC film also increased.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

The increase in fungal infections, accompanied by adverse effects and acquired resistance associated with the use of antifungal agents used for their clinical management, have facilitated the search for new substances with antifungal properties. Naphthoquinones have been investigated due to their multiple biological activities, including their significant antifungal potential. This study aimed at evaluating the antifungal potential of naphthoquinones against opportunistic fungi and dermatophytes and to assess the impact of a selected naphthoquinone on the formation of the cell wall, ergosterol membrane, and cellular membrane of Candida albicans ATCC 60193. Additionally, cytotoxicity in the MRC-(Medical Research Council-)5 cell lineage, Artemia salina, and tomato as well as arugula seeds was evaluated. The antifungal activity of four naphthoquinones was assessed using well-characterized fungal strains, the minimum inhibitory concentration (MIC) was determined applying the microdilution assay technique. Antifungal activity of the assessed naphthoquinones could be confirmed, particularly for 2,3-DBNQ (2,3-dibromo-1,4-naphthoquinone), which showed prominent antifungal activity (MIC of <1.56 - 6.25 µg/mL) in all chosen test settings. However, its toxicity in MRC-5 cells (IC50 = 15.44 µM), a recorded 100% mortality in A. salina at a concentration of 50 µg/mL, as well as inhibition of 94.8% of the tomato seeds at a concentration of 400 µg/mL and inhibition of 64.1% of arugula seeds at a concentration of 200 µg/mL may limit hypothetical therapeutic applications. It was demonstrated that the likely mechanism of action of 2,3-DBNQ involves interfering with fungal membrane permeability, leading to increased leakage of nucleotides. This study adds to available knowledge on antifungal effects of naphthoquinones, especially of 2,3-DBNQ, against opportunistic yeasts and dermatophytes. However, the observed cytotoxicity in the MRC-5 cell lineage, A. salina, as well as tomato and arugula seeds highlights a need for further research to optimize the selectivity and safety profile of naphthoquinones like 2,3-DBNQ before potential clinical use may be assessed.

A series of novel indole Schiff base derivatives (2a–2t) containing a 1,3,4-thiadiazole scaffold modified with a thioether group were synthesized, and their structures were confirmed using FT-IR, ¹H NMR, ¹³C NMR, andHR-MS. In addition, the antifungal activity of synthesized indole derivatives was investigated against Fusarium graminearum (F. graminearum), Fusarium oxysporum (F. oxysporum), Fusarium moniliforme (F. moniliforme), Curvularia lunata (C. lunata), and Phytophthora parasitica var. nicotiana (P. p. var. nicotianae) using the mycelium growth rate method. Among the synthesized indole derivatives, compound 2j showed the highest inhibition rates of 100%, 95.7%, 89%, and 76.5% at a concentration of 500 μg/mL against F. graminearum, F. oxysporum, F. moniliforme, and P. p. var. nicotianae, respectively. Similarly, compounds 2j and 2q exhibited higher inhibition rates of 81.9% and 83.7% at a concentration of 500 μg/mL against C. lunata. In addition, compound 2j has been recognized as a potential compound for further investigation in the field of fungicides.

Background: Biosurfactants are amphiphilic surface active compounds that produced by several microorganisms, including, bacteria and fungi. Biodegradability, low toxicity, applications diversity and functionality under extreme conditions are characterized them from chemically biosurfactants. It is found that, Rhodotorula species, read yeasts, have high potency for biosurfactant producing. Recently, antimicrobial activities of biosurfactants have been subjected for new antibiotic therapy. The aim of the present study was to evaluate biosurfactant production by the different strains of Rhodotorula species in laboratory conditions. In addition, antifungal activity of produced biosurfactant was assessed against several saprophytic fungi. In the present study 54 strains of Rhodotorula including, R. glutinis (48 strains), R. minuta (2 strains), R. mucilaginosa (2 strains) and Rhodotorula species (2 strains) were screened for biosurfactant production. The biosurfactant was produced using the Sabouraud dextrose broth medium and confirmed by specific tests. Antifungal assay was also evaluated by disk diffusion method and the serial dilutions of biosurfactant. In the present study, although all tested strains were capable to produce biosurfactant in vitro, the degree of biosurfactant production was varied among stains. 7.4% strains had the highest (+5) biosurfactant activity followed by 16.7%, 29.5%, 25.8% and 20.4% had +4, +3, +2 and +1, respectively. In the present study, all tested fungi were inhibited at 40 µl of biosurfactant. Rhodotorula species are appropriate organisms for the production of biosurfactants and R. glutinis strains have the greatest ability to producing biosurfactant than another species. Furthermore, our results were demonstrated that the produced biosurfactant by R. glutinis presented a valuable potential for biopharmaceutical applications.

In this review, we discuss novel natural products discovered within the last decade that are reported to have antifungal activity against pathogenic species. Nearly a hundred natural products were identified that originate from bacteria, alga, fungi, sponges and plants. Fungi were the most prolific source of antifungal compounds discovered during the period of review. The structural diversity of these antifungal leads encompasses all the major classes of natural products including polyketides, shikimate metabolites, terpenoids, alkaloids and peptides.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

With the increased scientific interest in green technologies, many researches have been focused on the production of polymeric composites containing naturally occurring reinforcing particles. Apart from increasing mechanical properties, these additions can have a wide range of interesting effects, such as increasing the resistance to bacterial and fungal colonization. In this work, different amounts of two different natural products, namely neem and turmeric, have been added to polyethylene to act as a natural antibacterial and antifungal product for food packaging applications. Microscopic and spectroscopic characterization showed that fractions up to 5% of these products can be dispersed into low-molecular weight polyethylene, while higher amounts could not be properly dispersed and resulted in an inhomogeneous, fragile composite. In vitro testing conducted with Escherichia coli, Staphylococcus aureus and Candida albicans showed a reduced proliferation of pathogens when compared to the polyethylene references. In particular, turmeric, resulted to be more effective against E. coli when compared to neem, while they had similar performances against S. aureus. Against C. albicans, only neem was able to show a good antifungal behavior, at high concentrations. Tensile testing showed that the addition of reinforcing particles reduces the mechanical properties of polyethylene, and, in the case of turmeric, it is further reduced by UV irradiation.

Fifty-two kinds of N’-phenylhydrazides were successfully designed and synthesized. Their anti-fungal activity in vitro against five strains of C. alb. was evaluated. All prepared compounds owned varying degrees of activity and their MIC80, TAI, and TSI values were calculated. The in-hibitory activities of 27/52 compounds against fluconazole-resistant fungi C. alb. 4395 and C. alb. 5272 were much higher than those of fluconazole. The MIC80 values of 14/52 compounds against fluconazole-resistant fungus C. alb. 5122 were less than 4 μg/mL, so it was the most sensitive fungus (TSIB = 12.0). A11 showed the highest inhibitory activity against C. alb. SC5314, 4395, and 5272. The antifungal activities of B14 and D5 against four strains of fluconazole-resistant fungi were higher than those of fluconazole. The TAI values of A11 (2.71), B14 (2.13), and D5 (2.25) are the highest. Further exploring the antifungal mechanism revealed that the fungus treated with compound A11 produced free radicals and reactive oxygen species, and their mycelium mor-phology was damaged. In conclusion, the hydrazide scaffold showed potential in the develop-ment of antifungal lead compounds. Among them, A11, B14, and D5 demonstrated particularly promising antifungal activity and hold potential as novel antifungal agents.

The morbidity and mortality caused by invasive fungal infections is increasing across the globe due to developments in transplant surgery, the use of immunosuppressive agents, and the emergence of drug-resistant fungal strains, which has led to a challenge in terms of treatment due to the limitations of three classes of drugs. Hence, it is imperative to establish effective strategies to identify and design new antifungal drugs. Drug repurposing is an effective way of expanding the application of existing drugs. In the last years, various existing drugs have been shown to be useful in the prevention and treatment of the invasive fungi. In this review, we summarize the currently used antifungal agents. In addition, the most up to date information on the effectiveness of existing drugs with antifungal activity is discussed. Moreover, the antifungal mechanisms of existing drugs are highlighted. These data will provide valuable knowledge to stimulate further investigation and clinical application in this field.

The paper provides a discussion on the results of studies of the effect exerted by combined degradation factors typical of four types of wear: abrasion, impact-abrasion, tribocorrosion, and impact-abrasion-corrosion, conducted for chain wheels made of Ni-Cu alloyed Austempered Ductile Iron. The studies consisted in determining the content of retained austenite in the structure of the cast irons in question, establishing the measures of wear following wear testing, and identifying basic surface degradation mechanisms observed in the chain wheels tested following multifactorial wear processes. The chain wheels made of ADI were found to have sustained the greatest damage under the impact-abrasion-corrosion (three-factor) wear scenario, while the wear was least advanced in the abrasion (one-factor) wear case. Another observation derived from the studies is that the combined effect of dynamic forces, corrosion, and quartz sand-based abrasives causes increased surface degradation in the cast iron grades taken into consideration compared to processes characterised by a reduced number of degradation factors (i.e. one- or two-factor wear processes). Additional hardness tests and XRD analyses have revealed a distinctive effect attributable to combined degradation factors on the surface hardness increase value and implied that bench testing was followed by phase transition.

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration-resistance is often developed during the course of treatment, though its influences require further understanding. This study explores the human microbiome for its implications in castration-resistance and metastasis in prostate cancer. RNA sequencing data was downloaded for bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These sequences were mapped to bacterial sequences to yield species-level abundance approximations. Numerous species were found to correlate to the expression of known markers of castration-resistance, including AR, PI3K, and AKT. Castration-resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for relation to these species. EGFR and SLC3A2 were widely downregulated with greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration-resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of prostate cancer, allowing for needed improvement in the treatment of this disease.

Modern technologies can satisfy human needs only with the use of large quantities of fertilizers and pesticides that are harmful to the environment. For this reason, it is possible to develop new technologies for sustainable agriculture. The process could be made by using endophytic microorganisms with a (possible) positive effect on plant vitality. Bacterial endophytes have been reported as plant growth promoters in several kinds of plants under normal and stress conditions. In this study, isolates of bacterial endophytes from the roots and leaves of Miscanthus giganteus plants were tested for the presence of plant growth-promoting properties and their ability to inhibit pathogens of fungal origin. Pantoea ananatis and Pseudomonas libanensis were the predominant bacteria in leaves whereas other pseudomonads prevailed in roots. Selected bacterial isolates were able to solubilize inorganic phosphorus, to fix nitrogen, and to produce IAA, ACC deaminase and siderophore. Leaf bacterial isolate Pantoea ananatis 50 OL 2 had high production of siderophores and weak capabilities for phytohormone production. The root bacterial isolate of Pseudomonas libanensis 5 OK 7A showed the best results of phytohormone production. Four fungal cultures - Fusarium sporotrichioides DBM 3229, Sclerotinia sclerotiorum SS-01, Botrytis cinerea and Sphaerodes fimicola were used to test the antifungal activity and these cultures were selected for their representatives of known pathogenic fungi families, especially for crops. All selected roots endophyte isolates significantly inhibited the pathogenic growth of Fusarium sporotrichoides with a mean inhibition diamater (zone ≥ 5 mm). These results demonstrated that the root endophytic Pseudomonas sp. could be used as biofertilizer for crops.

Nanosystems-based antifungal agents have emerged as an effective strategy to address issues related to drug resistance, drug release, and toxicity. Among the different materials used for drug delivery, multifunctional polymers have proven to be ideal due to their versatility. This review provides an overview of the various types of nanoparticles used in antifungal drug delivery systems, with a particular emphasis on the types of polymers used. The review focuses on the application of drug delivery systems and the release behavior of these systems. Furthermore, the review summa-rizes the critical physical properties and relevant information utilized in antifungal polymer nanomedicine delivery systems, and briefly discusses the application prospects of these systems.

Fungal infections impact the lives of at least 12 million people every year, killing over 1.5 million. Wide-spread use of fungicides and prophylactic antifungal therapy have driven resistance in many serious fungal pathogens, and there is an urgent need to expand the current antifungal ar-senal. Recent research has focused on improving azoles, our most successful class of antifungals, by looking for synergistic interactions with secondary compounds. Synergists can co-operate with azoles by targeting steps in related pathways, or they may act on mechanisms related to re-sistance like active efflux or on totally disparate pathways or processes. A variety of sources of potential synergists have been explored, including pre-existing antimicrobials, pharmaceuticals approved for other uses, bioactive natural compounds and phytochemicals, and novel synthetic compounds. Synergy can successfully widen the antifungal spectrum, decrease inhibitory dosag-es, reduce toxicity, and prevent the development of resistance. This review highlights the diversity of mechanisms that have been exploited for the purposes of azole synergy and demonstrates that synergy remains a promising approach for meeting the urgent need for novel antifungal strate-gies.

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

Fungal infections pose a significant threat to human health, particularly in immunocompromised individuals. Due to several factors, such as the inappropriate use of antimicrobial drugs, the emergence of resistance in microorganisms, and increasing demand for less cytotoxic antifungal agents for immunocompromised patients, antifungal research has gained significant attention in recent years. Antifungal peptides, and among them, cyclic peptides, are a class of antifungal agents that have been under development since the 1960s. Using cyclic peptides as a promising approach for combating antifungal resistance in pathogenic fungi has gained significant attention in recent years. The identification of antifungal cyclic peptides from various sources has been possible due to the widespread interest in peptide research in recent decades. It is increasingly important to evaluate the narrow to broad-spectrum antifungal activity and the mode of action of synthetic and natural cyclic peptides for both synthesized and extracted peptides. This short review aims to highlight some of the antifungal cyclic peptides isolated from bacteria, fungi, and plants, taking into consideration the progress made in peptide research. Additionally, it provides a summary of synthetic cyclic peptides with antifungal activity and discusses the potential future of utilizing combinations of antifungal peptides from different sources. The review underscores the need for further exploration of the novel therapeutic applications of these abundant and diverse cyclic peptides.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

Candida auris is considered an emerging Candida species that has rapidly spread all over the world. The evidence of its origin and emerging resistance is still unclear. The severe infection by this species causes significant mortality and morbidity among the elderly and immune compressed individuals. Development of drug resistance is the major factor associated with therapeutic failure of existing antifungal agents. Previous studies addressed the antifungal resistance profile and drug discovery for C. auris. However, comprehensive coverage of these information in a single investigation yet to be available. In this review, we have mainly focused on recent development in therapeutic strategy against C. auris. Based on the available information, several differential approaches were discussed, including existing antifungal drugs, chemical compounds, essential oils, natural products, antifungal peptides, immunotherapy, antimicrobial photodynamic therapy, drug repurposing, and drug delivery systems. Among them, chemical medications, natural products, and antifungal peptides are the prime contributors. However, a limited number of resources are available to prove the efficiency of these potential therapies in clinical usage. Hence, we hope that the data gathered in this review can encourage in vivo studies and clinical trials.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple medi-ation analysis revealed that all three potential mediators played a role in mediating the associa-tion. However, in the parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43—0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31—0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003—0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Background: The resurgence of syphilis, primarily in MSM populations, has necessitated novel prophylactic strategies, such as the use of doxycycline post-exposure prophylaxis (doxy-PEP). However, the potential for increased doxycycline use to select for tetracycline resistance represents significant challenges in managing this sexually transmitted infection. This study aims to identify chromosomal mutations associated with tetracycline resistance in Spirochaetales to inform treatment strategies and surveillance measures.Methods: Whole genome sequences (WGS) from the Spirochaetales order, including 4,355 genomes, were analyzed for the presence of mutations in 16S rRNA and non-synonymous mutations in the rpsC and rpsJ genes. The study utilized WGS from GenBank® and sequence data from the PubMLST Treponema pallidum isolate collection. Genetic resistance to tetracycline was detected using a combination of BLASTN searches and gene-gene analysis. Results: A transition mutation TGA to TGG at positions 965-967 in the 16S rRNA gene was detected in 5.6% of Treponema spp. and 3.97% of Spirochaeta spp. genomes. The rpsJ gene exhibited a V57G amino acid substitution across a significant subset of Treponema spp. Notably, the V57K mutation was common in Spirochaeta spp. The rpsC gene had the H178Q mutation and was found to be present in the Spirochaetales bacterium.Conclusion: The identification of mutations associated with tetracycline resistance in Spirochaetales provides a foundation for the development of rapid molecular diagnostics and guides the clinical selection of antibiotics for syphilis treatment. This study underscores the complexity of antibiotic resistance mechanisms and the critical importance of surveillance in the era of antibiotic prophylaxis for STI management.

Vulvovaginal candidiasis (VVC) is a prevalent condition affecting women worldwide. This study aimed to develop a rapid qPCR assay for accurate identification of VVC etiological agents and reduced azole susceptibility. One hundred and twenty nine vaginal samples from an outpatient clinic (Bilbao-Spain) were analyzed using culture-based methods and multiplex qPCR targeting fungal species, Candida albicans being the predominant species. Antifungal susceptibility tests revealed reduced azole susceptibility in three (3,48%) isolates. Molecular analysis identified several mutations in genes associated with azole resistance and novel mutations in TAC1 and MRR1 genes were also identified, which could contribute to drug resistance.

Broad-spectrum antifungal drug deployed for topical therapy, specific for onychomycosis, Itraconazole was used as the active pharmaceutical ingredient in a nail lacquer formulation¹. The objective of the study was to optimize an antifungal nail lacquer, which when applied topically onto the dorsal surface of the nail plate would facilitate the transungual penetration of the drug. Itraconazole hydrochloride was synthesized to aid the formulation of the lacquers. The optimization involved comparing four different formulations of 1%w/w Itraconazole nail lacquers containing combinations of penetration enhancers (Papain, Salicylic acid, Urea) based on their ability to facilitate diffusion of the drug through the nail plate over five days. The drug uptake was quantified by extracting the drug from the nail clippings and analyzing it. The tests conducted to account for the quality of the optimized formulation were drug content, spread ability, check for precipitation, and accelerated stability. The results demonstrated that the optimized 1%w/w Itraconazole nail lacquer contained 5%w/w Papain, 5 %w/w Salicylic Acid, and 2.8% w/w Urea. The drug uptake from nail clippings was higher than the literature derived reference MIC90 value for T. Rubrum strain, and the quality of the optimized lacquer was not compromised throughout three weeks [2]. The hypothesis stated that the inclusion of Salicylic acid, Papain, and Urea in an Itraconazole (1%w/w) nail lacquer would have the highest transungual penetration on application to the nail plate. In conclusion, the hypothesis was accepted, and the optimized lacquer passed the drug uptake evaluation and all quality control tests.

The carriage of Candida albicans in children's oral cavities is associated with a higher risk for early childhood caries, so controlling this fungus in early life is essential for preventing caries. In a prospective cohort of 41 mothers and their children from 0-2 years of age, this study addressed 4 main objectives: 1) Evaluate in vitro the antifungal agent susceptibility of oral Candida isolates from the mother-child cohort, 2) Compare Candida susceptibility between isolates from the mothers and children; 3) Assess longitudinal changes in the susceptibility of the isolates collected between 0-2 years; and 4) Detect mutations in C. albicans antifungal resistance genes. Susceptibility to antifungal medications was tested by in vitro broth microdilution and expressed as minimal inhibitory concentration (MIC). C. albicans clinical isolates were sequenced by whole genome sequencing, and the genes related to antifungal resistance, ERG3, ERG11, CDR1, CDR2, MDR1, and FKS1, were assessed. Four Candida spp (n=126) were isolated: C. albicans, C. parapsilosis, C. dubliniensis, and C. lusitaniae. Caspofungin was the most active drug for oral Candida, followed by fluconazole and nystatin. Two missense mutations in the CDR2 gene were shared among C. albicans isolates resistant to nystatin. Most of the children’s C. albicans isolates had MIC values similar to those from their mothers, and 70% remained stable to antifungal medications from 0-2 years. For caspofungin, 29% of the children’s isolates showed an increase in MIC values from 0-2 years. Results of the longitudinal cohort indicated that clinically used oral nystatin was ineffective in reducing the carriage of C. albicans in children; novel antifungal regimens in infants are needed for better oral yeast control.

Background : Probiotics are composed of microorganisms that have positive effects on health when consumed in prescribed quantities. Lately, studies have attempted to establish this role of probiotics in enhancing health. Aim : The aim of this study was to compare the antifungal activity of 3 different probiotics against Candida albicans.Methodology :This was an in-vitro study. 3 types of commercially available probiotics - Bifilac, Pre pro HS and VSL-3 were cultured separately with Candida albicans and were placed under incubation. The maximum zone of inhibition was recorded for each of the probiotic solutions.Results : In this study, it was found that among the three probiotic products, Bifilac exhibited a maximum zone of inhibition of 13mm at concentration of 100µL against C. albicans, while Pre pro HS and VSL-3 showed zone of inhibition of 11mm at concentrations of 50µL and 100µL, respectively.Conclusion : Within the limits of the present study, This study could prove that probiotics can be considered as an alternative and safe treatment option for treatment of Oral candidiasis infections.

Filamentous fungi such as Aspergillus spp. are opportunistic pathogens, which cause highly invasive infections, especially in immunocompromised individuals. Control of such fungal pathogens is increasingly problematic due to the small number of effective drugs available for treatment. Moreover, the increased incidence of fungal resistance to antifungal agents makes this problem a global human health issue. The cell wall integrity system of fungi is the target of antimycotic drugs echinocandins, such as caspofungin (CAS). However, echinocandins cannot completely inhibit the growth of filamentous fungal pathogens, which results in survival/escape of fungi during treatment. Chemosensitization was developed as an alternative intervention strategy, where co-application of CAS with the intervention catalyst octyl gallate (OG; chemosensitizer) greatly enhanced CAS efficacy, thus achieved ≥ 99.9% elimination of filamentous fungi in vitro. Based on hypersensitive responses of Aspergillus antioxidant mutants to OG, it is hypothesized that, besides destabilizing cell wall integrity, the redox-active characteristic of OG may further debilitate fungal antioxidant system.

Abstract Plant fungal pathogens are frequently found as one of limiting factors for crop production. More than 10,000 species of fungi can cause disease in plants. To control the diseases, many farmers are still rely on the use of chemical fungicides, however most synthetic fungicides can cause acute toxicity, and some cause chronic toxicity as well. Thus, an appropriate technological improvement towards a more effective use of natural resources is required in agriculture to develop environmentally friendly sustainable farming system. This paper highlights the potential of extracts of tropical plants as antifungal agent to control plant fungal diseases. Information and data presented in this paper are mainly derived from selected and related references that previously published in the scientific journals. Many higher plants of tropical origin with fungicidal activities and their potential for fungal disease control of agricultural crops have been studied, however most of the studies have been done under in vitro condition. Some plant extracts showed strong antifungal activities on in vitro as well as in vivo tests, but some plant extracts showed significant antifungal activities on in vitro test, but did not obvious on in vivo tests. A great variation in antifungal activities were shown by plants extracts of different species and plant parts, in one hand, and on the other hand, variation was also observed on the responses of different fungal species to the same plant extract. Since the purpose of the use of plant extract is to control plant fungal diseases, the field trial is needed to ensure the stability of efficacy of certain plant extract. In addition, isolation and identification of active substances in the extracts is needed to assess possible mode of action and side effect of their use.

Sporotrichosis’ clinical manifestations, lesions in the cutaneous or subcutaneous tissues, it is caused by dimorphic fungi of the Sporothrix complex, is a cosmopolitan mycosis that affects humans and animals. This study aimed to identify prevalent species in Minas Gerais, Brazil, and characterize virulence profiles and antifungal susceptibility associated with Sporothrix isolates. Isolates were identified using macro and micro-morphological traits as well molecular biology techniques. Antifungal susceptibility was determined using the Minimal Inhibitory Concentration test, while, virulence factors such as growth at different temperatures, biofilm formation, melanin production, and urease activity were assessed. Our findings revealed S. brasiliensis as a predominant species isolated. Urease activity was a crucial factor associated with growth at 50°C in S. brasiliensis isolates, highlighting their high thermotolerance. Furthermore, strains isolated from humans produced a more robust biofilm compare to those from felines. Strains of S. brasiliensis isolated from Felis catus exhibited faster melanin production, decreased susceptible to antifungal agents tested, and superior growth capacity at 50°C to strains isolated from humans. Therefore, our study highlights the prevalence of S. brasiliensis causing sporotrichosis in both human and felines. However, it underscores the circulation of different strains, with varying levels of virulence and susceptibility to antifungal agents.

Addressing the growing need for effective and environmentally friendly fungicides in agricul-ture, this study explored the potential of alginate microparticles loaded with metal ions as a novel approach to combat fungal pathogens. Novel alginate microparticles (microspheres and microcapsules) loaded with zinc or simultaneously with zinc and silver ions were prepared and physicochemically characterized (microparticle size, morphology, topography, encapsulation efficiency, loading capacity, and swelling behavior). Investigation of molecular interactions in microparticles using FTIR-ATR spectroscopy exhibited complex interactions between all con-stituents. Fitting to the simple Korsmeyer-Peppas empirical model revealed the rate-controlling mechanism of zinc and silver ions release from microparticles is Fickian diffusion. Lower values of the release constant k imply a slower release rate of Zn or Ag ions from microcapsules com-pared to that of microspheres. The antimicrobial potential of the new formulations against the fungus Botrytis cinerea was evaluated. When subjected to tests against the fungus, microspheres and microparticles loaded with both zinc and silver ions effectively reduced its growth and al-tered the fungal hyphal structures well as exhibited superior antifungal activity. The results showed the potential of these novel microparticles as potent fungicides in agriculture.

The dynamic resistance is an important parameter in flux pumping. It is simple to calculate in slab geometry but more complex in tapes. In this paper another simple geometry is analysed which is a wire loop. To do this it is essential to make clear what is meant by the term 'voltage', which is ambiguous when there are alternating magnetic fields present. The term can be used if it refers to the EMF along a specified path. However this means that results are dependent on how the voltage leads are attached. If the n value of the V-I characteristic is large simple analytic expressions can be obtained. This will be referred to as the 'Bean' model solution. A more exact approach uses Faraday's law to derive a differential equation which is solved and compared with the Bean model. The dynamic resistance of the loop can be used to drive a flux pump of the type proposed by Geng and Coombs [4] and again simple expressions can be obtained for the performance. If the load is of high inductance L2 and the loop has an inductance L1 then the load current increases exponentially with a characteristic number of cycles L2/L1. The final current can be close to the critical value.

To estimate the progressive collapse resistance capacity of a multi-column frame tube structure with the assembled truss beam composite floor (ATBCF), the pushdown analysis, and the nonlinear dynamic analysis as well, are conducted for such a structure by using the alternate load path (ALP) method. The bearing capacities of the remaining structures at three different work conditions, which are the side middle column failure, the edge middle column failure, and the corner column failure, are individually studied, and the collapse mechanism for the remaining structures is analyzed from the aspects of the internal force redistribution and the failure mode of the second defense line. Simultaneously, the influence of the column failure time on the dynamic response of the remaining structure and the dynamic amplification coefficient are discussed. The results show that the residual bearing capacity of the remaining structure with the bottom corner column failure is higher than that of the one with the side or edge middle column failure, while the latter has a stronger plastic deformation capacity. When the ALP method is adopted to operate the progressive collapse analysis, it is reasonable to take the column failure time as 0.1 times of the first-order vertical vibration period of the remaining structure, and it is suitable to set the dynamic amplification coefficient as of 2.0, which is the ratio of the maximum dynamic displacement to the static displacement of the remaining structure under the transient loading condition.

In searching for compounds with antioxidant and antifungal activity, our study focused on the subshrub species Empetrum rubrum Vahl ex Willd. (Ericaceae), commonly known as Brecillo or Murtilla de Magallanes. We measured the antioxidant activity of its methanolic extract (MEE) obtained from the aerial parts (leaves and stems). The antioxidant activity of MEE was evaluated in vitro by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical and 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) cationic radical. Results were expressed in gallic acid and Trolox equivalents for DPPH and ABTS assays, respectively. The antioxidant activities, for the DPPH and ABTS assays, were also calculated as an inhibitory concentration of extract needed to inhibit 50% of the absorbance (IC50 value). The results of IC50 values measured by the DPPH and ABTS methods were 0.4145 mg mL-1 and 0.1081 mg mL-1, respectively. In relation to the antioxidant activity, the total phenolic content (TPC) in MEE was determined by the Folin-Ciocalteu method, and the presence of secondary metabolites groups, including phenolic compounds, was determined by using different standardized test procedures. Phenolic compounds contained in leaves, stems, and fruits of E. rubrum were determined qualitatively by means of high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) analysis. The antifungal activity of MEE obtained from aerial parts of E. rubrum was tested against Rhizoctonia solani. In vitro, mycelial growth of this fungus was reduced from 90% to 100% in the presence of MEE.

Developing nanomaterials with the capacity to restrict the growth of bacteria and fungus is of current interest. In this study, nanocomposites of poly(2-hydroxyethyl methacrylate) (PHEMA) and carbon nanotubes (CNTs) functionalized with primary amine, hydroxyl, and carboxyl groups were prepared, and characterized. An analysis by Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy showed that PHEMA chains were grafted to the functionalized CNTs. The morphology of the prepared nanocomposites studied by field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM) shows significant changes with respect to the observed for pure PHEMA. The thermal behavior of the nanocomposites studied by differential scanning calorimetry (DSC) revels that the functionalized CNTs affects strongly the mobility of the PHEMA chains. Tests carried out by thermogravimetric analysis (TGA) were used to calculate the degree of grafting of the PHEMA chains. The ability of prepared nanocomposites to inhibit the growth of the fungus Candida albicans, and the bacteria Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli was evaluated. A moderated antifungal and antibacterial capacity of the prepared nanocomposites was determined.

Salinity is one of the major factors responsible for the deterioration of soils, making them unsuitable for agriculture. The application of halotolerant and halophilic plant growth promoting bacteria (PGPR: Plant Growth Promoting Rhizobacteria) with biological control activities as an inoculant of cultivated plants offers a biological alternative to the use of agrochemicals, particularly when subjected to salt stress. In this perspective, 70 bacterial strains were isolated from saline soils (sebkha) in arid and semi-arid areas of eastern Algeria. Three isolates were selected based on their ability to produce bioactive molecules allowing them to promote plant growth, such as hydrolytic enzymes, indole acetic acid, HCN, NH3, etc. Two of these isolates belong to the genus Serratia and the third is a halophilic Halomonas bacteria. These bacteria were identified based on the 16S rDNA sequence. Antagonism tests against phytopathogenic fungi were carried out. The identification of the antifungal molecules produced by these bacteria was done by high performance liquid chromatography. These bacteria are capable of inhibiting mycelial development against phytopathogenic fungi with rates reaching 80.67% against Botrytis cinerea, 76.22% against Aspergillus niger and 66.67% against Fusarium culmorum for Serratia sp. The strain Halomonas sp. inhibited mycelial growth by production of volatile substances of Aspergillus niger at 71.29%, Aspergillus flavus at 75.49% and Penicillium glabrum at a rate of 72.22%. The identification by HPLC of the antifungal molecules produced by these three bacteria reveals that they are polyphenols, which makes these strains the first rhizobacteria capable of producing phenolic compounds. Finally, pot tests to determine the effectiveness of these strains in promoting wheat growth under salinity stress (125 mM, 150 mM and 200 mM) were carried out. The results revealed that a consortium of two isolates (Serratia sp. and Halomonas sp.) performed best at 125 mM. But, at higher concentrations it was the halophilic bacteria Halomonas sp which gave the best result. In all cases, there was a significant improvement in the growth of wheat seedlings inoculated with the bacteria, compared to non-inoculated controls.

The development of multidrug resistance by pathogenic bacteria and yeast is a significant medical problem that needs to be addressed. One possible answer could be the combined use of antibiotics and silver nanoparticles, which have different mechanisms of antimicrobial action. Nanoparticles can be combined with antifungal agents in the same way. Biogenic silver nanoparticles synthesized using environmentally friendly technology using extracts of biologically active plants are an effective nanomaterial that needs to be comprehensively investigated for implementation into medical practice. In this study, the synergistic effects arising from their combined use with antibiotics and fungicides against various bacteria and yeasts, included in the ESKAPE list, were studied. Effective concentrations of substances were established, recommendations for the studied pathogenic species were presented and the effect of destruction of the bacterial membrane was illustrated. The most significant synergistic effect was manifested in pathogenic candida and brewer's yeast.

Olive mill wastewater (OMW) has serious environmental problems considering its high organic matter, especially its phenolic compounds. The OMW application in crop protection is an alternative environmentally eco-friendly method reducing the chemicals pesticides impact on human health and environment. The present work aimed to study the antifungal activity of fresh and stored OMW and its ethyl acetate extract against phytopathogenic fungi: Syncephalastrum racemosum (S. racemosum), Paramyrothecium roridum (P. roridum), Fusarium oxysporum (F. oxysporum) and Verticilium dahlia (V. dahlia). The OMW was stored at 25 and 45 °C for 3 months. Fresh and stored OMW were used non-sterile, sterile and centrifuged. Phenolic and flavonoid compounds were extracted and identified by HPLC analysis. High inhibition of studied fungi was shown by fresh OMW and its derivative compounds, while OMW storage, sterilization, and centrifugation increased mycelium growth of studied fungi, especially S. racemosum that showed a relative resistance against stored OMW effect and its ethyl acetate extract. Under storage conditions, some phenolic and flavonoid compounds disappeared (resorcinol and vanillic acid), while the concentration of other compounds increased (gallic acid, chlorogenic acid and quercetin). This work highlighted the ability to use fresh OMW as a bio-agent to protect plants from fungi diseases.

Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.

Carvacrol has long been studied for its natural antifungal potential and food preservative. But the exact mode of its action remained highly complex as a general, but especially for Penicillium digitatum (P. digitatum) largely remained unexplored. Herein, a 1H-NMR-based metabolomic technique was used to investigate the antifungal mechanism of carvacrol. The metabolomic profiling data showed that alanine, aspartate, glutamate and glutathione metabolism were imbalanced in the fungal hyphae. A strong positive correlation was seen between aspartate, glutamate, alanine and glutamine, while negative correlation among glutathione and lactate. These metabolic changes revealed that carvacrol-induced oxidative stress had disturbed the energy production and amino acid metabolism of P. digitatum. Current study will improve the understanding of the metabolic changes posed by plant-based fungicides in order to control citrus fruit green mold caused by P. digitatum. Moreover, the study will provided certain experimental and theoretical basis for the development of novel citrus fruit preservatives.

Viroids are known the smallest plant pathogens, and although their genome sequences do not encode proteins, they can cause disease in economically important crops. In order to control viroid diseases and mitigate their damage, genetic resources used for breeding of the viroid-resistant crop have been searched, but the practical resistant trait has not been found in almost all viroid-crop combinations, as well as the tolerant trait. Due to the difficulty in exploiting naturally occurring resistance or tolerance, various effective strategies have been devised to control viroid diseases using non-transforming or transforming techniques. Meanwhile, extensive findings related to viroid resistance and tolerance may lead to confer resistance or tolerance to viroid infection by combining with the recently emerged new technologies (e.g., spray-induced gene silencing and genome-editing technologies), which are believed to be more environmentally viable and acceptable to the general public than previously reported approaches. In particular, some genome-modified crops produced by the latter technology are already on the market. In this review, we comprehensively summarize the current status about investigation of naturally occurring genetic traits for viroid resistance and tolerance, accumulating knowledge about host factors involved in viroid pathogenicity, and various basic technologies developed to try to possible viroid disease control strategies. Furthermore, we discuss prospects and challenges for the achievement of more effective, practical, and sustainable disease control of viroid.

The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as by elemental analysis and by HR-MS. The structure of a n-hexane monosolvate has been determined by single crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677 and C. tropicalis ATCC 64677) has been tested, using the disk diffusion and the microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.

Plant pathogenic fungi are the most important cause of losses in agriculture. In the face of the overuse of synthetic fungicides, natural products are an encouraging alternative to control these plant pathogenic fungi. In this study, we tested the antifungal capacity of metabolites produced by strains of the genus Streptomyces against the plant pathogenic fungi Alternaria alternata, Botrytis cinerea and Fusarium oxysporum. In addition, we investigated the feasibility of applying these metabolites in a postharvest setting for the control of B. cinerea on cherry tomato fruits. The results revealed the ability of the strains, especially Streptomyces netropsis, to inhibit the growth of plant pathogenic fungi and, in some cases, the sporulation of these fungi. In addition, we observed an interesting phenomenon in which Streptomyces strains physically encapsulated the mycelium of the fungi, which contributed to their inhibition. Finally, the protective activity of S. netropsis extract on Cherry tomato fruits infected with B. cinerea was demonstrated. In conclusion, this research opens the door to studies on the understanding of physical microbial interactions in natural environments and holds promise in agriculture, especially in the protection of agricultural products during the post-harvest stage as a safer and more sustainable alternative.

Eysenhardtia platycarpa (Fabaceae) is a medicinal plant used in México and it lacks biotechnological studies for its use. The aim of this work was to establish a cell suspension cultures (CSC) of E. platycarpa, determine the phytochemical profile, and evaluate its antifungal activity. Friable callus and CSC were established with 2 mg/L 1-naphthaleneacetic acid plus 0.1 mg/L kinetin. The highest total phenolics of CSC was 15.6 mg GAE/g dry weight and the total flavonoids content ranged from 56.2 to 104.1 µg QE/g dry weight. CG‒MS analysis showed that the dichloromethane extracts of CSC, sapwood and heartwood have a high amount of hexadecanoic acid (22.3 ‒ 35.3 %) and steroids (13.5 ‒ 14.7%). Heartwood and sapwood defatted hexane extracts have the highest amount of stigmasterol (≈ 23.4%) and β-sitosterol (≈ 43%), and leaf extracts presented β-amyrin (16.3%). Methanolic leaves extracts showed mostly sugars and some polyols, mainly D-pinitol (74.3%). Dichloromethane and fatty hexane extracts of CSC exhibited the percentages inhibition higher for Sclerotium cepivorum with 71.5 and 62.0%, respectively. The maximum inhibition for Rhizoctonia solani was with fatty hexane extracts of the sapwood (51.4%). Our study suggest that CSC extracts could be used as a possible complementary alternative to synthetic fungicides.

Classical Hodgkin lymphoma (cHL) is a highly curable disease (70-80%), even though long-term toxicities, drug resistance, and predicting clinical responses to therapy are major challenges in cHL treatment. To solve these problems, we characterized two cHL cell lines with acquired resistance to doxorubicin, KM-H2dx and HDLM-2dx (HRSdx), generated from KM-H2 and HDLM-2 cells, respectively. HRSdx cells developed cross-resistance to vinblastine, bendamustin, cisplatin, dacarbazine, gem-citabine, brentuximab vedotin (BV), and γ-radiation. Both HDLM-2 and HDLM-2dx cells had an intrinsic resistance to BV but not to the drug MMAE. HDLM-2dx acquired cross-resistance to caelyx. HRSdx cells had in common: decreased CD71, CD80, CD54, cyt-ROS, HLA-DR, DDR1, CD44; increased Bcl-2, CD58, COX2, CD26, CCR5, invasive capability; increased CCL5, TARC, PGE2, TGF-β, and capability to hijack monocytes. In HRSdx cells, less sensitive to DNA damage and oxidative stress, the efflux drug transporters MDR1 and MRP1 were not up-regulated, and doxorubicin accumulated in cytoplasm rather than in nucleus. Both autophagy inhibitor chloroquine and extracellular vesicles (EVs) release inhibitor GW4869 enhanced doxorubicin activity and counteracted doxorubicin resistance. In conclusion, this study identifies common modulated antigens in HRSdx cells, the associated cross-resistance patterns, and new potential therapeutic options to enhance doxorubicin activity and overcome resistance.

Abstract: Vulvovaginal candidiasis (VVC) is a mucous membrane infection, with an increased rate of antifungal resistance of Candida species. The in vitro efficacy of farnesol alone or in combination with traditional antifungals, against resistant Candida strains recovered from women with VVC was assessed. In this study, 80 Candida isolats were identified by multi-plex PCR. Antifungal sus-ceptibility of amphotericin B (AMB), fluconazole (FLU), itraconazole (ITZ), voriconazole (VOR), clotrimazole (CTZ) and farnesol was tested by M27-A3/S4 broth micro dilution method. The combinations of farnesol with each antifungal were calculated based on the fractional inhibitor concentration index (FICI). C. glabrata was the predominant species (48.75%) isolated from vaginal discharges, followed by C. albicans (43.75%), C. parapsilosis (3.75%), mixed infection of C. albicans and C. glabrata (2.5%), C. albicans and C. parapsilosis (1%). C. albicans and C. glabrata isolates had lower susceptibility to FLU (31.4% and 23.0%, respectively) and CTZ (37.1% and 33.3%, respectively). Importantly, there was ‟synergismˮ between farnesol-FLU and farnesol-ITZ against C. albicans and C. parapsilosis (FICI= 0.5 and 0.35, respectively), reverting the original azole resistant profile. These findings indicate that farnesol is able to revert to the resistance profile of azole by enhancing the activity of FLU and ITZ in resistant isolates, which is a promising result.

Globally increasing antibiotic resistance has been connected to the use of antibiotics in medical, veterinary, and agricultural medicine, contributing to the burden of antibiotic resistance in Asia and Europe. The main objective of this study was to correlations of antimicrobial-resistant of various pathogens in three compartments: humans, animals and the environment in India and Germany. A systematic search was carried out in Medline via PubMed, Google Scholar, and science direct, including studies published in 2022. Out of 532 papers, 24 were considered for meta-analysis. This study reveals that in India, β-lactam is highly resistant in animals. Quinolone, on the other hand, was highly resistant in humans. Furthermore, in the environment and integrated studies, aminoglycosides and β-lactams is resistant. While in Germany, a high rate of AMR resistance in all three sectors was reported in β-lactam. However, E. coli was the most frequent pathogen in both countries and is highly resistant to β-lactam, followed by cephalosporin in all the compartments. Monitoring and evaluating antibiotic-sensitivity patterns and developing proper antibiotic regimens may lead to improved outcomes for inhibiting and controlling E. coli infections in various parts of the world.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

The growing increase in infections caused by C. tropicalis, associated with its drug resistance and consequent high mortality, especially in immunosuppressed people, today generates a serious global public health problem. In the search for new potential drug candidates that can be used as treatments or adjuvants in the control of infections by these pathogenic yeasts, the objective of this research was to evaluate the action of isoespintanol (ISO) against the formation of biofilms fungal, the mitochondrial membrane potential (∆Ψm) and its effect on the integrity of the cell wall. We report the ability of ISO to inhibit the formation of biofilms by up to 89.35%, in all cases higher than the values expressed by amphotericin B (AFB). Flow cytometric experiments using rhodamine 123 (Rh123) showed the ability of ISO to cause mitochondrial dysfunction in these cells. Likewise, experiments using calcofluor white (CFW) and analyzed by flow cytometry, showed the ability of ISO to affect the integrity of the cell wall by stimulating chitin synthesis; these changes in the integrity of the wall were also observed through transmission electron microscopy (TEM). These mechanisms are involved in the antifungal action of this monoterpene.

The article describes facile one-pot, hi-yielding reactions to synthesize substituted 3,4-dimethyl-1H-pyrrole-2-carboxamide (3a–m) and carbohydrazide analogues (5a–l) as potential antifungal and antimicrobial agents. The structural integrity and purity of the synthesized compounds were assigned based on appropriate spectroscopic techniques. Synthesized compounds were assessed in vitro for antifungal and antibacterial activity. The compound 5h, 5i and 5j were found to be the most potent against A. fumigatus, with MIC value of 0.031 mg/mL. The compound 5f bearing a 2,6-dichloro group on the phenyl ring was found to be the most active broad spectrum antibacterial agent with MIC value of 0.039 mg/mL. The mode of action of the most promising antifungal compounds (one representative from each series; 3j and 5h) was established by their molecular docking to the active site of sterol 14α-demethylase. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds in the access channel away from catalytic heme iron of the enzyme, which suggested that the tested compounds inhibit this enzyme and would avoid heme iron related deleterious side effects observed with existing antifungal compounds.

In this work, the resistance/susceptibility (R/S) profile of Staphylococcus equorum strains (n=30) from cheese to 16 antibiotics was determined by broth microdilution. The minimum inhibitory concentration (MIC) for all antibiotics was low in most strains, although higher MICs compatible with acquired genes were also noted. Genome analysis of 13 strains showed the S. equorum resistome to be composed of intrinsic mechanisms, acquired mutations, and acquired genes. However, the genetic data did not always correlate with the phenotype. As such, a cat gene providing resistance to chloramphenicol was found on a plasmid in one strain; this was able to provide resistance to Staphylococcus aureus after electroporation. An msr(A) polymorphic gene was identified in five strains. The Mrs(A) variants were associated with variable resistance to erythromycin. All strains harboured a polymorphic fosB/fosD gene, although only one acquired copy was associated with strong resistance to fosfomycin. Similarly, a plasmid-associated blaR1-blaZI operon encoding a penicillinase was identified in five ampicillin- and penicillin G-susceptible strains. Identified genes not associated with resistance further included mph(C) in two strains and norA in all strains. The antibiotic R/S status and gene content of S. equorum strains intended to be employed in food systems should be carefully determined.

The ergosterol pathway is a prime antifungal target. The minimum inhibitory concentration (MIC) assay is a simple research tool that determines the lowest concentration at which a novel antimicrobial with limited scope to determine the mechanism of action for a drug. In this study, we show that by adding hydrogen peroxide, an oxidative stressor, or glutathione (GSH), an antioxidant, to modify a commonly performed MIC assay allowed us to screen selectively for new antifungal drugs that target ergosterol biosynthesis in fungi. A human pathogen, Microsporum gypseum, was used as a test organism. When exposed to ergosterol targeting drugs, the hydrogen peroxide treatment significantly decreased fungal survival by reducing ergosterol in the cell wall, whereas GSH increased survival of M. gypseum. Further, by performing a series of experiments with M. gypseum, it was determined that the oxidative stress from hydrogen peroxide causes cell death at different developmental stages. These findings allow us to describe a simple, high-throughput method for simultaneously screening new antifungal drugs for activity and effects on the ergosterol pathway. By using this tool, two isoquinoline alkaloids were discovered to be potent inhibitors of ergosterol biosynthesis by reducing the amount of ergosterol without affecting the expression of 1,3-β-glucan.

The use of Lactic Acid Bacteria (LAB) for probiotic enrichment of minimally processed fruit is a well-established practice in literature. In addition, several LAB demonstrated a strain-specific ability to control harmful microorganisms and decay agents, improving shelf-life, maintaining quality and promoting the safety of fruits and vegetables. Edible coatings can help modulate phenomena of gas exchange and water loss by fruits, representing protection from physical damage and spoilage phenomena linked to oxidation and the development of undesired microorganisms. At the same time, the coating can represent an innovative delivery matrix for the LAB strains of potential interest to improve safety and quality in the postharvest management of fruits. In this work, five Lactiplantibacillus plantarum strains, previously characterized for their probiotic and antifungal activity, have been incorporated into a sodium alginate coating to develop edible probiotic coatings with antifungal properties for table grapes cv. Italia. The transfer of probiotics and their survival were evaluated by comparing coated and uncoated table grapes during 14 days of cold storage at 4 °C. The alginate edible coating increased the number of probiotics transferred to the surface of the berries from about 5 to more than 7 Log CFU/g, with a crucial impact on the potential functional attributes of the final product. The ability of the functionalised coatings to counteract the decay development was evaluated on table grapes berries artificially contaminated with Aspergillus niger CECT 2805. A significant reduction of lesion diameter was observed in alginate coating with L. plantarum 11-A. The lesion diameter reduction was also accompanied by the reduction of the symptoms of infection, such as browning around the wound. These results suggest the application of selected strains of L. plantarum as promising bio-resources to enhance the overall value of ready-to-eat fruits and vegetables, particularly in combination with edible coating as a carrier matrix. While a strain-dependent effect was not detected with respect to the improvement of the number of cells in the edible coating, a variability depending on the biotype used was detected for the properties linked to biocontrol, suggesting that the inclusion in edible packaging may represent an innovative criterion in the selection of lactobacilli to be applied postharvest.

The rhizosphere is a rich source of actinomycetes which can produce several potential biologically-active secondary metabolites. The principal goals for this research are to extract, purify and characterize the bioactive secondary metabolites produced by three different strains of actinomycetes isolated from the rhizosphere of rosemary, black locust and olive. The plant growth-promoting effect (PGPE) of the studied strains of actinomycetes on Ocimum basilicum L. (basil) and disease-control effect on necrotic stem lesions of “black leg” caused by Fusarium tabacinum on basil, were in silico evaluated. The cell-free culture filtrates from the studied actinomycetes isolates were evaluated in vitro for their antimicrobial activity against some common phytopathogens. The secondary metabolites obtained from the cell-free culture filtrates have been chemically characterized using high‐resolution electrospray ionization of liquid-chromatography/mass-spectrometric detection (ESI-(HR)Orbitrap-MS). Results of in silico trial showed that all studied isolates demonstrated PGPE on basil seedlings improving some Eco-physiological characteristics and reduced the disease incidence of F. tabacinum. The extracted metabolites from the studied actinomycetes demonstrated antimicrobial activity in Petri-plates assay. The chemical analysis revealed the presence of totally 20 different components. This research emphasizes how valuable the examined isolates are for producing bioactive compounds, indicating their putative antimicrobial activity and their potential employment as fungal-biocontrol agents. In particular, the obtained results revealed the possibility of green-synthesis of some important secondary metabolites such as N-Acetyl-L-histidinol, Rhizocticin A and Eponemycin from actinomycetes. The bioactive metabolites may be successively used to develop novel bio-formulations for both crop protection and/or PGPE.

The investigation by the integrated approach newly introduced for this study indicates that insulin resistance (IR) would develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue, to the visceral adipose tissue, and to the liver with higher cell turnovers. Moreover, metabolic disruptions due to IR vary widely from tissue to tissue, contrary to the conventional notion that IR merely impairs glucose uptake in the whole body. This warrants that IR be divided better into four distinct tissue specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Tissue-specific IRs developing in the order of MIR, s-AIR, v-AIR, and HIR – producing tissue specific metabolic disruptions – would amount to nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin resistant stages. The four stage metabolic evolution from rapid weight gain to visceral obesity to rapid weight loss to full blown diabetes not only complies well with the natural development history of diabetes but also resolves most of the controversies regarding obesity or diabetes, including visceral obesity, obesity paradox, and dawn phenomenon that have long remained metabolic puzzles. In addition, the four-stage WBIR evolution model refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but supports instead the glycation-induced insulin resistance (GIIR) proposed in this study. A speculation is that the glycation reaction activated ever more with WBIR evolving may serve as the common thread connecting each other a cluster of disorders or diseases that are often collectively referred to as the metabolic syndrome, such as obesity, diabetes, cardio/cerebral vasculopathy, nephropathy, neuropathy, and retinopathy.

Influenza viruses cause acute respiratory infections responsible for significant mortality and morbidity around the world. Various factors, such as antigenic drift, allow influenza strains to avoid being fully suppressed by seasonal vaccines. This has led to the increased scrutiny of antivirals as treatment and prophylaxis options for seasonal outbreaks and potential pandemics. Unfortunately, many influenza antivirals suffer from a lack of adequate clinical trials, as well as a lack of toxicity data. This is especially true of umifenovir (arbidol), a drug popularly used for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, though widely prescribed, display a potential for future resistance. Adamantanes, while proven to be effective in treating influenza A, are already encountering rapid and widespread cross-resistance and are effectively obsolete. Baloxavir marboxil, a newer antiviral, shows promise in treating acute uncomplicated influenza and may avoid the development of resistance when co-administered with other antiviral drugs. Indeed, the low genetic barrier to resistance associated with influenza antivirals could potentially be overcome by co-administration with other antivirals. This review explores the most widely prescribed antivirals for influenza treatment, their mechanisms of action, and the data currently available about their susceptibility to resistance and efficacy.

Human exposure to antimicrobial resistance (AMR) through food is now very imperfectly understood, creating a significant gap in the design of interventions. The interchange of AMR genes and the transfer of AMR bacteria from animals to humans through the food chain necessitate comprehensive methods to risk reduction. With a focus on AMR in bacterial species isolated from food products, foods (of both animal and non-animal origin), and ambient samples, the current meta-analysis gathered up-to-date information on the epidemiology of AMR in animal-source food chain. As a result, the combined prevalence of AMR across the various food sources was calculated. From the 18,784 food samples obtained as a result of selected publications, 7,676 (40.9%) samples were contaminated, including 4343 (56.6%) and 3363 (43.4%) samples from Taiwan and India, respectively. Meat (chicken, pork, and beef), fish and milk all have moderate to medium potential for AMR exposure to both Gram-positive and Gram-negative foodborne pathogens such S. aureus, Clostridium, E. coli, Salmonella, etc. Antibiotic resistance to β-lactam, fluoroquinolone, carbapenem etc, is present in the majority of food samples. The results of this study emphasize the persistent danger of antimicrobial residue in animal-derived foods in Taiwan, India, and other nations with comparable customs.

As the prevalence of antimicrobial resistance genes is increasing in microbes, we are facing the return of the preantibiotic era. Consecutively, the number of studies concerning antibiotic resistance and its spread in the environment is rapidly growing. Next generation sequencing technologies are widespread used in many areas of biological research and antibiotic resistance is no exception. For the rapid annotation of whole genome sequencing and metagenomic results considering antibiotic resistance, several tools and data resources were developed. These databases, however can differ fundamentally in the number and type of genes and resistance determinants they comprise. Furthermore, the annotation structure and metadata stored in these resources can also contribute to their differences. Several previous reviews were published on the tools and databases of resistance gene annotation, however, to our knowledge, no previous review focused solely and in depth on the differences in the databases. In this review, we compare the most well-known and widely used antibiotic resistance gene databases based on their structure and content. We believe that this knowledge is fundamental for selecting the most appropriate database for a research question and for the development of new tools and resources of resistance gene annotation.

Rosette caused by rose rosette virus (RRV) is the most devastating malady of rose in the United States. Because of the recent discovery of the virus and the completion of Koch’s postulates all assumptions about the disease are based on visual observations of material that may or may have not been infected by the virus. This study addresses several aspects of virus and disease epidemiology. Twenty rose genotypes were screened for mite and/or virus resistance. Phyllocoptes fructiphilus the only known vector of RRV, was able to establish, lay eggs and develop to nymphs and adults in all genotypes. ‘Stormy Weather’ shows resistance to the virus as assessed by both mite and cleft-grafting transmission experiments. The acquisition/latent and inoculation access periods were studied revealing long acquisition/latent periods but rapid inoculation time frames. The outputs of this study will assist in the better management of the vector and the disease. The resistant genotype identified could be used in areas with high disease pressure to minimize spread and for identification of the mechanisms behind resistance or as breeding material to incorporate virus resistance to new cultivars. The short inoculation access period indicates that chemical control for the vector may be a challenging undertaking.

Decoctions, macerations and fumigations of the stem bark and wood of Terminalia brownii Fresen. are used in traditional medicine for fungal infections and as pesticides on field crops and in traditional granaries in Sudan. In addition, T. brownii is commonly used for protecting wooden houses and furniture. Therefore, using agar disc diffusion and macrodilution methods, eight extracts of various polarities from the stem wood and bark were screened for their growth inhibitory effects against filamentous fungi commonly causing fruit, vegetable and grain decay, as well as infections in the immunocompromised host. Ethyl acetate extracts of the stem wood and bark gave the best antifungal activities, with MIC values of 250 µg/ml against Nattrassia mangiferae and Fusarium verticillioides, and 500 µg/ml against Aspergillus niger and Aspergillus flavus. Aqueous extracts gave almost as potent effects as the ethyl acetate extracts against the Aspergillus and Fusarium strains, and were slightly more active than the ethyl acetate extracts against Nattrassia mangiferae. Thin layer chromatography, RP-HPLC-DAD and tandem mass spectrometry (LC-MS/MS), were employed to identify the chemical constituents in the ethyl acetate fractions of the stem bark and wood. The stem bark and wood were found to have a similar qualitative composition of polyphenols and triterpenoids, but differed quantitatively from each other. The stilbene derivatives, cis- (3) and trans- (4) resveratrol-3-O-β-galloylglucoside, were identified for the first time in T. brownii. Moreover, methyl-(S)-flavogallonate (5), quercetin-7-β-O-di-glucoside (8), quercetin-7-O-galloyl-glucoside (10), naringenin-4`-methoxy-7-pyranoside (7), 5,6-dihydroxy-3`,4`,7-tri-methoxy flavone (12), gallagic acid dilactone (terminalin) (6), a corilagin derivative (9) and two oleanane type triterpenoids (1) and (2) were characterized. Our results justify the traditional uses of macerations and decoctions of T. brownii stem wood and bark for crop and wood protection and demonstrate that standardized extracts could have uses for the eco-friendly control of plant pathogenic fungi in African agroforestry systems. Likewise, our results justify the traditional uses of these preparations for the treatment of skin infections caused by filamentous fungi.

The promising antimicrobial activity of essential oils (EOs) led researchers to use them in combination with antimicrobial drugs in order to reduce drug toxicity, side effects, and resistance with single agents. In Pancalieri (Turin, Italy), there is a local production of Mentha x piperita worldwide known as “Mentha of Pancalieri”. The EO from this Mentha is considered as one of the best peppermint EO in the world. In our research, we assessed the antifungal activity of “Mentha of Pancalieri” EO either alone or in combination with azole drugs (fluconazole, itraconazole, ketoconazole) against a wide panel of yeast and dermatophyte clinical isolates. The EO was analyzed by GC-MS and its antifungal properties were evaluated by MIC/MFC parameters, according to the CLSI guidelines, with some modifications. The interaction of peppermint EO with azoles was evaluated through the chequerboard and isobologram methods. Results suggest this EO exerts a fungicidal activity against yeasts, and a fungistatic activity against dermatophytes. Interaction studies with azoles indicate mainly synergistic profiles between itraconazole and peppermint EO vs. Candida spp., Cryptococcus neoformans and Trichophyton mentagrophytes. Peppermint of Pancalieri EO may act as a potential antifungal agent and may serve as a natural adjuvant for fungal infection treatment.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has been proven a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

Antimicrobial resistance (AMR) is a growing public health issue worldwide that affects the world economy. The concern associated with this issue increased during the COVID-19 pandemic. The misuse of antibiotics during the COVID-19 pandemic will have catastrophic implications for the control of AMR. In 2019, the coronavirus illness COVID-19 first appeared in China. COVID-19 infection is a surface-to-surface communicable disease. It is considered the most vital global health disaster of the century. It has rapidly spread around the world and is the greatest challenge for humankind. This chapter discusses the origin, symptoms, transmission, treatment, and recommendations of the COVID-19 disease.

In sustainable agriculture, plant nutrients are the most important elements. Biofertilizers introduce microorganisms that improve the soil nutrients and increase their accessibility to crops. In order to meet the demands of a growing population, healthy crops need to be produced using the right type of fertilizers to provide them with all the major nutrients they require. However, an increasing dependency on chemical fertilizers is destroying the environment and negatively af-fecting the health of humans. Thus, using microbes as bioinoculants as the best replacement of chemical fertilizers as eco-friendly way for plant growth and soil fertility is believed to be the best method for improving plant growth and soil fertility. In sustainable agriculture, these microbes provide significant benefits to crops. In addition to colonizing plant systems (epiphytic, endo-phytic, and rhizospheric), beneficial microbes play a key role in absorbing nutrients from surrounding ecosystems. Plant associate microbes can promote plant growth regardless of natural and extreme conditions. Plant growth promoting microbes promote plant growth through a variety of direct and indirect methods, such as nitrogen fixation, plant growth hormone production, siderophores, HCN, several hydrolytic enzymes, and potassium, zinc, and phosphorus solubilization. Research on biofertilizers has been extensive and even available, which demonstrates how these microbes can deliver nutrients to crops in sufficient quantities to enhance their yield. This review examines in detail the direct and indirect mechanisms of PGPR action and their interaction in plant growth and resistance.

To identify soil microbial communities, it is essential to understand their phenotypic and genetic characteristics. Plant growth-promoting rhizobacteria (PGPR) are bacteria capable of promoting plant growth. In addition, rhizobacteria also serve as biological control agents. In addition to fixing atmospheric nitrogen, solubilising insoluble phosphate and secreting hormones such as indoloacetic acid, kinetics and gibberellins, plant growth-promoting rhizobacteria help plants grow directly. Furthermore, they facilitate plant growth indirectly by inducing systemic resistance, siderophores, antibiotics, lytic enzymes, hydrogen cyanide production and stress regulation. This review examines in detail the direct and indirect mechanisms of PGPR action and their interaction in plant growth and resistance.

Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis and highlight various ways through which tumor cells reprogram normal cells including into phenotypes that are pro-tumorigenic including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to formation of new vascular networks in order to actively promote and sustain tumor growth via supply of oxygen and nutrients whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to targeting of tumor cells. Re-programming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centred therapies under investigations.

Background: Public misconception and demand for the indication of antibiotics could lead to inappropriate prescribing and consumption. Successful treatment can only be achieved when the public and industrial users have knowledge on antibiotic use and resistance. This survey is aimed to assess antibiotic usage and knowledge regarding antibiotics and antimicrobial resistance (AMR) among undergraduate students of Universiti Brunei Darussalam (UBD), public university located in Brunei Darussalam. Methods: A cross-sectional study was performed using a self-administered questionnaire. The questionnaire was adapted from the World Health Organization (WHO) Antibiotic Resistance, Multi-country public awareness survey distributed online. Students at UBD were invited to participate in the online survey through internal email. The questionnaire consisted of 5 sections: demographic information, antibiotic usage, knowledge on antibiotics, antibiotic resistance (AMR) and use of antibiotics in agriculture. Data were analyzed descriptively and appropriate inferential statistics was used accordingly. Cronbach’s alpha was also done to determine the internal consistency. The section on antibiotic use and knowledge showed good internal consistency of Cronbach’s alpha 0.66 and 0.86 respectively. Research ethics approval was obtained from the PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam (UBD). Results: A total of 145 students returned the complete questionnaire. The result of the study found that 50% of the students had good level of knowledge of antibiotic and antimicrobial resistance with a mean total knowledge score of 11.4 out of 14. Respondents reported the use of antibiotic in the past (69%). Many of the students could identify the use of antibiotics for the treatment of bacterial infection. However, there were also students who incorrectly thought that antibiotics can be used for cold and flu (43%) and fever (41%). Moreover, 76% of the respondents mistakenly believed that antibiotic resistance is the result of the body becoming resistant to antibiotics. Only 12% of the respondents were found to have poor knowledge in the study. Conclusions: Misconceptions in regards to the use of antibiotics for conditions related to viral illnesses was noticed among the respondents in our study. Thus, improving knowledge on antibiotics is crucial to address those beliefs.

Let G[F,Vk, Huv] be the graph with k pockets, where F is a simple graph of order n ≥ 1,Vk= {v1,v2,··· ,vk} is a subset of the vertex set of F and Hvis a simple graph of order m ≥ 2,v is a specified vertex of Hv. Also let G[F,Ek, Huv] be the graph with k edge pockets, where F is a simple graph of order n ≥ 2, Ek= {e1,e2,···ek} is a subset of the edge set of F and Huvis a simple graph of order m ≥ 3, uv is a specified edge of Huvsuch that Huv− u is isomorphic to Huv− v. In this paper, we derive closed-form formulas for resistance distance and Kirchhoff index of G[F,Vk, Hv] and G[F,Ek, Huv] in terms of the resistance distance and Kirchhoff index F, Hv and F, Huv, respectively.

Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increas the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, for example, for -manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance. This review focused onpossibilities and limitations of the proposed regulation of the resistance of normal cells whole organisms to genotoxic and oxidative stress by overexpressing of stress-response genes. Moreover, the existing experimental data on the effect of such overexpression on the resistance of cells and organisms to various genotoxic agents has been analyzed and systematized. We suggest that the recent advances in the development of multiplex and highly customizable gene overexpression technology that utilizes the mutant Cas9 protein and the wealth of available data on gene functions and their signal networks open new opportunities for research in this field.

Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Anti-fungal drug resistance and cytotoxicity highlight the need for effective antifungal therapeutics. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed, Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. the doubling time was also drastically affected, going from 2.8 hours to 22.5 hours. Which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cy-totoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the po-tential mechanisms of A. occidentale against C. albicans on a cellular level and might provide a promising op-tion for the design of a new treatment for invasive candidiasis

Microbiocontrol of Mycogone perniciosa is focused on casing soil antagonists use. Since no industrial producer strains of polyfunctional biologics were used in previous studies, research goal was to characterize Bacillus subtilis B-10 and M-22 effect on mycopathogen and reveal its control possibilities. Interactions between producer strains and M. perniciosa were evaluated using well method and spraying. Mycoparasite colony area and its lysis zone were determined. Biological efficacy was characterized by lysis zone proportion in total area occupied by the micromycete mycelium. Statistical processing included W-test, ANOVA, means (M) and standard errors (±SEM) calculation. The significance was assessed by t-test. M. perniciosa development suppressing by producer strains was established, indicates a prolonged B-10 and M-22 effect on mycopathogen. High biological efficacy of both strains at the early stages of mycopathogen development by introducing into the wells and spraying was shown: B-10 – 50.9–99.6 % and M-22 – 57.5–99.2 % respectively (p ≤ 0.05). Significant differences between producer strains were not revealed, although during the first exposure day to developed M. perniciosa colonies M-22 has shown greater activity. Preventive treatment high efficiency when producer strains completely suppressed mycoparasite development, permit recommending them both to introduce when preparing casing for M. perniciosa control.

Background: Scientific literature on COVID-19 is still limited about long-term impacts on the all-body systems and they treatments. The aim of the study was to create a safe protocol-based in-tervention to improve functional and equilibrium abilities in older adults impacted by COVID-19. Methods: The study completed 46 people (intervention group: n=26; control group: n=20). Re-sistance training (RT) was held twice a week, 60 min per session for 8 weeks. The postural stability and quality of life questionnaire (WHQOOL) were conducted during pre- and post-testing. Results: Results indicated significant differences in overall stability index (OSI) with eyes open (EO), ante-rior-posterior stability index (APSI) EO, fall risk index 6-2 (FRI6-2) values in males (p

Aspergillus flavus is a pathogenic fungus that affects and contaminates several foodstuffs and is associated with cancer in humans. In Senegal, significant losses of groundnut production are mainly due to contamination caused by this species. This study evaluated in vitro antifungal activities of Cyperus articulatus, Cyperus rotundus and Lippia alba essential oils against A. flavus isolated from peanut seeds. Essential oils obtained by hydrodistillation of rhizomes of the two Cyperus species and leaves of L. alba were analyzed by GC-DIF and GC-MS. The essential oil yields from C. articulatus, C. rotundus and L. alba were 1.1%, 1.3% and 1.7%, respectively. These three samples had the following chemotypes: (i) Mustakone (21.4%)/eudesma-4(15)-7-dien-1β-ol (8.8%)/caryophyllene oxide (5.9%), (ii) caryophyllene oxide (25.2%)/ humulene epoxyde 2 (35.0%) and (iii) geranial (46.6%)/neral (34.6%). The three oils tested inhibited the growth of A. flavus at concentrations between 100 and 1000 ppm. The L. alba oil was the most effective with total clearance of A. flavus on PDA. For the essential oils of C. rotundus (93.65%) and C. articulatus (78.11%), the highest inhibition rates were obtained with 1000 ppm dose. Thus, the L. alba oil could be used safely as an effective protector of groundnuts against A. flavus.

Skid resistance of a road pavement surface is the force developed when tyre is prevented from rotating slides along the pavement sur-face. This property comes from the combination of the macro- and micro-texture of pavement. The skid resistance of an asphalt pave-ment is an important parameter influencing driving safety on a road, since there is a proven relationship between skid resistance and accident parameters. The paper deals with the measurement principle of pavement skid resistance (surface friction) including longitudinal and transverse friction. A high number of measuring devices of skid resist-ance are also introduced highlighting their advantages and limitations. Besides, the measurement policies in the European Union and in Hun-gary are outlined. Pavement surface texture is investigated dealing with the levels of surface tex-ture, the most common measuring tech-niques, the macro-texture features of asphalt types, as well as the Hungarian regulation in the field. As a related topic, the aggregate properties and their implication in the relevant Hungarian specification are introduced briefly, as well. Some outcomes of the EU’s COST Ac-tion 354 on the development of unified European macro-roughness and skid resistance performance indicators and indices are also presented.

Introduction Tuberculosis is common in Pakistan. Due to various factors including socioeconomic factors, compliance is poor to anti-tuberculosis drugs, leading to resistance. We aim to determine the prevalence of Multidrug resistance (MDR) tuberculosis in Pakistani population.Methods A prospective observational study was conducted from April 1, 2019, to December 31, 2019, in the Pulmonology department of a tertiary care hospital in Pakistan. Culture and sensitivity were assessed using a sputum sample or, in cases of an absent sputum sample, from Broncho alveolar lavage.ResultsApproximately 71.3% percent patients who had tuberculosis were found to be resistant to Isoniazid and around 48.6% did not respond to Rifampin. Multi-drug resistant was found in 29.4% participants.ConclusionMulti-drug resistance tuberculosis is very prevalent in Pakistan, which may increase burden on health care system and may lead to various complications of tuberculosis.

Activating mutations in the Epidermal Growth Factor Receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20-30% of patients do not respond or respond for a very short time (< 3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.

Salmonella enterica serovar Typhi, is one of the major infection spreading from consuming contaminated food and water. The poor sanitation is one the major cause for successful infection. S. typhi is responsible for causing typhoid fever, which is a growing public health concern in developing countries. This bacterium has acquired antimicrobial resistance to many promising which is a growing health concern for community. This study is aim to elucidate the molecular complexity of flouroquinolone resistance in S. Typhi isolates (n=286). Genomic data was downloaded from NCBI and analysis was done by Resfinder, MLST, and Pointfinder. Genomic analysis unveils a complex resistance profile, featuring antimicrobial resistance genes (ARG) including blaCTXM-15, blaTEM-1D, catA1, dfrA7, qnrS1, sul1, sul2, and tetA(B). The investigation focuses on mutations in DNA gyrA, parC, and qnrS1 genes which plays an important role in quinolone resistance. Mutation analysis reveals mutations such as DNA gyrA_S83F, DNA gyrA_D87N, DNA gyrA_S83Y, DNA gyrB_S464F, parC_S80I, and parE_L416F with the presence of qnrS1 gene produces resistance against quinolones. The Docking studies was conducted by “Autodock vina” and visualize by “Discovery studio” which demonstrate that these mutations leads to ciprofloxacin resistance, indicating reduced binding affinity, and altered solvent accessibility which indicates the structural changes at mutation sites. This study provides crucial insights into the molecular mechanisms driving flouroquinolone resistance in S. typhi, guiding future strategies to combat antibiotic resistance. Further validation through experimental mutagenesis is recommended, for targeted therapeutic interventions against the mounting threat of antibiotic-resistant S. typhi.

The aim of this investigation is to offer a data-based scheme for predicting electrode wear in resistance spot welding. Electrode wear and alloying is one of the most significant factors that affect the mechanical properties of spot welds and the variation in weld quality. In this study, Rogowski coils and twisted pairs attached to the top and bottom electrodes were used to obtain the welding current and the inter-electrode voltage in the welding process, thereby calculating the dynamic resistance value during the welding process. The electrode diameter was obtained from the pressure exerted by the upper and lower electrodes on the carbon paper when the current was cut off and was regarded as an indicator of electrode wear. By continuously welding 0.5mm thick BH 340 steel plates until the electrode failed, the dynamic resistance signal was recorded in real time. Simultaneously, the electrode diameter after every 4 welds was also recorded. On this basis, the correlation between electrode diameter and dynamic resistance is studied. In order to quantitatively study the mapping relationship between dynamic resistance and electrode wear, 11 characteristic values were extracted from the dynamic resistance, and the stepwise regression method was used to obtain the regression formula between the characteristic values and the electrode diameter. Using new data to verify the effectiveness of the regression model, the acquired results display that the maximum error between the predicted value of the electrode diameter and the measured value obtained by the regression equation with the interactive quadratic term is 0.3 mm, and the corresponding relative error is 7.69 %. This result demonstrates that the method proposed in this paper can effectively monitor the electrode wear and failure process.

The normal ageing process significantly affects resistance arteries, leading to various biological and physiological consequences. Systolic hypertension is a common occurrence in ageing individuals, accompanied by increased large artery stiffening, heightened pulsatility, small artery remodeling, and damage to critical microvascular structures. Starting from young adulthood, there is a progressive elevation in mean arterial pressure, supported by clinical and epidemiological evidence as well as findings from animal models. The myogenic response, a protective mechanism for the microcirculation, may face disruptions during ageing. Dysregulation of calcium entry channels (T-type, L-type, TRP channels), dysfunction in intracellular calcium storage and extrusion mechanisms, altered expression of potassium channels, and a change in smooth muscle calcium sensitization may contribute to age-related dysregulation of myogenic tone. Flow-mediated vasodilatation, a hallmark of endothelial function, is compromised in ageing. This result of endothelial dysfunction is related to oxidative stress, lower nitric oxide bioavailability and a low-grade inflammatory response, further exacerbating vascular dysfunction. Resistance artery remodeling in ageing emerges as a hypertrophic response of the vessel wall, often seen in conjunction with outward remodeling (in normotension), but can also present as inward hypertrophic remodeling (in hypertension). The remodeling process involves oxidative stress, inflammation, reorganization of extracellular matrix fiber proteins and actin cytoskeletal components. Reactive oxygen species (ROS) signaling and chronic low-grade inflammation, often referred to as "inflammaging”, play substantial roles in age-related vascular dysfunction. Due to its role in regulation of vascular tone as well as structural proteins, the RhoA/Rho-kinase pathway becomes a new target in age-related vascular dysfunction and associated diseases. Understanding the intricate interplay of these factors is crucial for developing targeted interventions to mitigate the consequences of ageing on resistance arteries and enhance overall vascular health.

Animal trypanosomiasis (AT) is a complex of veterinary diseases known under various names such as nagana, surra, dourine and mal de caderas, depending on the country, the infecting trypanosome species and the host. AT is caused by parasites of the genus Trypanosoma, and the main species infecting domesticated animals are T. brucei brucei, T. b. rhodesiense, T. congolense, T. vivax, T. evansi and T. equiperdum. AT transmission, again depending on species, is through tsetse flies or common Stomoxys and tabanid flies or through copulation. Therefore, the geographical spread of all forms of AT together is not restricted to the habitat of a single vector like the tsetse fly and currently includes almost all of Africa, and most of South America and Asia. The disease is a threat to millions of companion and farm animals in these regions, creating a financial burden in the billions of dollars to developing economies as well as serious impacts on livestock rearing and food production. Despite the scale of these impacts, control of AT is neglected and under-resourced, with diagnosis and treatments being woefully inadequate and not improving for decades. As a result, neither the incidence of the disease, nor the effectiveness of treatment is documented in most endemic countries, although it is clear that there are serious issues of resistance to the few old drugs that are available. In this review we particularly look at the drugs, their application to the various forms of AT, and their mechanisms of action and resistance. We also discuss the spread of veterinary trypanocide resistance and its drivers, and highlight current and future strategies to combat it.