To characterize the fecal microbiota of lactating Bactrian camels, this study employed a random selection of camels, assigning them to three groups: the first parity group, the third parity group, and the fifth parity group. The fecal microbial community of lactating camels was assessed using 16S rRNA amplicon sequencing, and the resulting library was sequenced on an Illumina NovaSeq platform. The first parity group was characterized by Verrucomicrobiaceae as a distinctive bi-omarker, whereas Clostridiaceae exhibited a similar role to the third parity group. In terms of functional analysis, the relative abundance of the Steroid biosynthesis pathway was highest in the first parity group, whereas the fifth parity group demonstrated a higher relative abundance of the Tuberculosis pathway compared to the other groups. The first parity group exhibited the greatest presence of seven types of enzymes, whereas the fifth parity group displayed the highest levels of two specific enzymes. Additionally, a positive association was observed between the relative abundance of the Steroid biosynthesis pathway and Verrucomicrobiaceae. Furthermore, the relative abundance of the Tuberculosis pathway displayed positive correlations with 14 enzymes. In conclusion, this study revealed that different parity was associated with distinct fecal microbial ecologies in lactating Bactrian camels.

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.

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.

The study aims to evaluate the Quorum Sensing (QS) system inhibition against some Gram-positive and Gram-negative bacteria detected by molecular modeling of R. cathartica L. plant extract. R. cathartica L. methanol extract was evaluated in vitro. The research was carried out for the possible role and mechanism of R. cathartica L. The antibacterial activity of R. cathartica L. seed extract on some Gram-positive and Gram-negative strains was evaluated using culture-based and computational analysis. Gentamicin (CN; 30 µg/ml, Bioanalyse) was used as an antibacterial control of the extract on the production potential of QS-dependent virulence factors on Pseudomonas aeruginosa PAO1 was investigated. Phytochemical analysis resulted in the identification of 23 phenolic phytochemicals. R. cathartica L. extract was observed to have antimicrobial activity against Gram-positive and Gram-negative bacteria at different rates (11.3 mm-16 mm). The inhibitory effect of R. cathartica L. extract on P. aeruginosa PAO1 (elastase 61%, pyocyanin 18%, and biofilm 61%) was recorded moderately. Phytochemical analysis revealed that the main component of the extract is kaempferol. Therefore, the binding potential of kaempferol on QS system receptors was investigated via molecular docking. Computational analysis showed that kaempferol can inhibit the QS system by preventing competitive ligands from connecting to LasR. This study explored the activity and mechanism of action for a new green alternative against resistance. might provide a mechanism for R. cathartica L. seed extract components and thus provide a new avenue for using R. cathartica L. seed extract as a green antibacterial agent.

Abstract: Escherichia coli are remarkably versatile microorganisms and important members of the normal intestinal microbiota of humans and animals. This harmless commensal organism can acquire a mixture of comprehensive mobile genetic elements that contain genes encoding viru-lence factors, becoming an emerging human pathogen capable of causing a broad spectrum of intestinal and extraintestinal diseases. Nine definite enteric E. coli pathotypes have been well characterized, causing diseases ranging from various gastrointestinal disorders to urinary tract infections. These pathotypes employ many virulence factors and effectors subverting the func-tions of host cells to mediate its virulence and pathogenesis. This review summarizes new de-velopments in our understanding of diverse virulence factors associated encoding genes used by different pathotypes of enteric pathogenic E. coli to cause intestinal and extraintestinal diseases in humans.

The type 6 protein secretion system (T6SS) is prevalently utilized by Gram-negative bacteria to compete for resources and space. Upon activation, toxic effectors from this secretion system are translocated into the competitor prokaryote or eukaryote in a contact-dependent manner. While much has been reported on T6SS-mediated prokaryotic competition, very little is understood about the mechanisms of bacterial interactions with eukaryotic hosts. Likewise, many virulent T6SS effectors are known to be antibacterial. In recent years, however, evidence has emerged on numerous T6SS effectors that interact with related immunity proteins in a range of eukaryotic hosts. Insights into how this effector-immunity pairing alters the physiological responses of the recipient organism might provide opportunities relating to the T6SS agricultural and biotherapeutic applications. We, therefore, summarize the impacts of the T6SS effectors with a special focus on bacterial interactions with animals, plants, and fungi. We further briefly discuss pipelines that are currently used to characterize antieukaryotic T6SS effectors.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

In volleyball, the jump serve is a fundamental and crucial skill that is one of the most commonly used serving techniques. This study aimed to examine the kinematic differences between straight line (SL) and diagonal line (DL) in volleyball jump serves by focusing on torso and attack arm joint motions. Three-dimensional coordinate data were captured using a motion capture system (200 Hz) in 14 right-handed male professional volleyball players who performed SL and DL jump serves. This result suggests that the pelvis and torso backward rotation angles during the arm-clocking phase were smaller when performing DL serves. During ball contact, the servers exhibited greater forward rotation angles of the pelvis and torso to control the upper body facing the diagonal direction of the target zone. In addition, lowering the forward tilt angle of the trunk helped the servers maintain body balance in the air and increased their wrist flexion angle, preventing the ball from flying out of bounds when performing DL. These findings highlight the importance of controlling pelvic and torso rotations in the transverse plane when adjusting for different serving lines. These insights can guide volleyball athletes and coaches in refining their serving techniques.

Of late, the focus has been shifted towards quorum sensing inhibitors which reduce bacterial virulence and lower the probability of resistance and refining infections. In this work, meta-bromo-thiolactone (mBTL), a potent quorum and virulence inhibitor against Staphylococcus aureus and MRSA phenotypes, was formulated in chitosan nanoparticles (ChNPs) using ionic gelation method. mBTL-loaded-ChNPs were characterized for particle size, polydispersity index, zeta potential. Morphology was visualized by Transmission Electron Microscopy (TEM), drug release profile and antibiofilm analysis using Confocal Laser Scanning Microscope (CLSM) and Scanning Electron Microscopy (SEM) were performed. Synthesized mBTL-loaded-CNPs showed homogenized nano-size particles ranging from 158+1.3 to 284+5.6 nm with spherical particles that exhibited sustainable release profile over 48 hr at 37 °C. These findings revealed successful preparation of mBTL-loaded-ChNPs, that further showed effective antibiofilm activity at MIC50 (0.5 mg/mL) where all strains displayed reduced biofilm formation compared to untreated strains. CLSM results showed a significant reduction in the number of viable cells, indicating the effectiveness of m-BTL as an antibacterial agent. SEM analysis permitted visualization of biofilm structure in relation to the spatial localization of important biofilm matrix components, the formed biofilms were clearly distinguished in the SEM images. Bacterial cells in the control group were enclosed in thick biofilms. In contrast, there was a considerable reduction in biofilm production when mBTL was present, where bacterial cells seemed less ordered and more scattered with no detectable biofilms. In conclusion, mBTL-loaded-ChNPs is a potential alternative treatment to overcome antimicrobial resistance and condensed MRSA infections.

Due to the progression of antimicrobial resistance, Photodynamic (aPDT) and Sonodynamic (SDT) Therapies arose as promising approaches for microbial control. Recently, the combination of both therapies, called Sonophotodynamic Therapy (SPDT), have shown greater effects than the single treatments. This study evaluated the effects of aPDT, SDT and SPDT mediated by curcumin on the metabolism, adhesion capacity, biofilm formation ability and structural alteration in the Staphylococcus aureus biofilm. Moreover, possible antimicrobial mechanisms involved, such as the production of reactive oxygen species (ROS) and the degradation spectrum of curcumin by light, ultrasound and light+ultrasound, were measured. SPDT was more effective to inactivate the biofilm than aPDT and SDT. All treatments reduced the adhesion ability of the bacteria and it is probably related to the metabolism cell reduction. Regarding to the biofilm formation ability, all treatments reduced the total biomass. One possible mechanism involved in the inactivation is the ROS production observed. Curcumin had a significantly decay in its absorbance with the application of light, and a slighter one caused by the ultrasound. Finally, all treatments impacted the biofilm components and structure, reducing the cells and matrix. In conclusion, SPDT was more effective in the inactivation, and all treatments had the same effect in the virulence factors evaluated.

Enterococci are widely acknowledged as prominent pathogens in hospitals, with the potential to transfer resistance genes, virulence factors, or other characteristics that increase their ability to survive in humans. Healthy cattle, sheep, and goats can be reservoirs for gastrointestinal pathogenic fecal enterococci, some of which could be multidrug-resistant to antimicrobials. The objective of this study was to determine the prevalence and diversity of Enterococcus species in healthy sheep, goat, and cattle carcasses, as well as to analyze the antimicrobial resistance phenotype/genotype and the virulence gene content. During 2019–2020, carcass surface samples of 150 ruminants were collected in a slaughterhouse. A total of 90 enterococci, comprising 5 species, were obtained. The overall prevalence of enterococci was found to be 60%, out of which 37.7% were identified as E. hirae, 33.3% as E. casseliflavus, 15.5% as E. faecium, 12.2% as E. faecalis, and 1.1% as E. gallinarum. Virulence-associated genes of efaA (12.2%) were commonly observed in the Enterococcus isolates, followed by gelE (3.3%), asaI (3.3%), and ace (2.2%). Characteristic resistance genes were identified by PCR with an incidence of 6.6%, 2.2%, 1.1%, 1.1%, 1.1%, and 1.1% for the tetM, ermB, ermA, aac(6’)Ie-aph(2")-la VanC1, and VanC2 genes, respectively. The high resistance to quinupristin-dalfopristin (28.8%), tetracycline (21.1%), ampisilin (20%), and rifampin (15.5%) was distributed among two, four, four, and five of the five species, respectively. The resistance of Enterococcus isolates to 11 antibiotic groups was determined and multidrug-resistant (MDR) strains occupied 18.8% of the Enterococcus isolates. Efflux pump genes causing multidrug resistance were detected in Enterococcus isolates (34.4%). The study's results showed that there were enterococci in the slaughterhouse that were multidrug resistant (MDR) and had a number of genes linked to virulence that could be harmful to human health.

Biofilm formation and lipopolysaccharide (LPS) are implicated in the pathogenesis of gastrointestinal (GI) diseases caused by Gram-negative such as Escherichia coli and Salmonella enterica serovar Typhimurium. Grape seeds, wine industry by-products, have antioxidant, antimicrobial, and anti-inflammatory activities. In the present study, the protective effect of procyanidin-rich grape seed extract (prGSE), from unfermented pomace of Vitis vinifera cv Bellone, on bacterial LPS-induced oxidative stress and epithelial barrier integrity damages has been studied in a model of Caco-2 cells. The in vitro activity of prGSE against formation of biofilm of S. Typhimurium and E. coli, has been investigated. In vivo, prGSE activity using infected Galleria mellonella larvae has been evaluated. The results showed that the prGSE, if administered with LPS, can significantly reduce the LPS-induced permeability alteration. Moreover, the ability of the extract to prevent Reactive Oxygen Species (ROS) production induced by LPS treatment of Caco-2 cells has been demonstrated. prGSE inhibited the biofilm formation of E. coli and S. Typhimurium. In in vivo activity, increased survival of infected G. mellonella larvae after treatment with prGSE has been demonstrated. In conclusion, grape seed extracts could be used in the reduction of GI damage caused by bacterial endotoxin and biofilm of Gram-negative bacteria.

Metformin (MeT) is an FDA-approved drug with a myriad of health benefits. Besides being used as an anti-diabetic drug, MeT is also effective against various cancers, liver-, cardiovascular-, and renal diseases. It has also been proven to demonstrate anti-ageing and neuroprotective effects. This study was undertaken to examine its unique potential as an anti-virulence drug against an opportunistic bacterial pathogen, Pseudomonas aeruginosa. Due to the menace of multidrug resistance in pathogenic microorganisms, many novel or repurposed drugs with anti-virulence prospects are emerging as next-generation therapies with the aim to overshadow the application of existing antimicrobial regimens. The quorum sensing (QS) mechanisms of P. aeruginosa are an attractive drug target for attenuating bacterial virulence. In this context, the anti-QS potential of MeT was scrutinized using biosensor assays. MeT was comprehensively evaluated for its effects on different motility phenotypes, virulence factor production (phenotypic and genotypic expression) along with biofilm development in P. aeruginosa in vitro. At sub-lethal concentrations, MeT displayed prolific quorum quenching (QQ) ability and remarkably inhibited AHL biosynthesis in P. aeruginosa. Moreover, MeT (1/8 MIC) effectively downregulated the expression levels of various QS- and virulence genes in P. aeruginosa, which coincided with a notable reduction in the levels of alginate, hemolysin, pyocyanin, pyochelin, elastase, and protease production. In silico analysis through molecular docking also predicted strong associations between the QS receptors of P. aeruginosa and MeT. MeT also compromised the motility phenotypes and successfully abrogated biofilm formation by inhibiting EPS production in P. aeruginosa. Hence, the QQ, anti-virulence, and anti-fouling potential of MeT was elucidated for the first time against P. aeruginosa.

The objective of this paper was to verify the applicability of statistical learning (SL) compared to human reasoning with respect to the Universal Thermal Climate Index (UTCI), a complex tool for the assessment of outdoor thermal stress. UTCI is an equivalent temperature index based on the 48-dimensional output of an advanced model of human thermoregulation formed by 12 variables at four consecutive 30-minute intervals, which were calculated for 105642 thermal conditions from extreme cold to extreme heat. Comparing the performance of SL algorithms to the results accomplished by an international endeavor involving more than 40 experts from 23 countries, we found that random forests and k-nearest neighbors closely predicted UTCI values, but that clustering applied after dimension reduction algorithms (principal component analysis and t-distributed stochastic neighbor embedding) were inadequate for risk assessment in relation to the UTCI stress categories. This indicates a potential supportive role for SL, as it will not (yet) fully replace the bio-meteorological expert knowledge.

The enormous potential of renewable bioresources is expected to play a key role in the development of the EU’s sustainable circular economy. In this context, inexhaustible, biodegradable, non-toxic and carbon-neutral forest-origin resources are very attractive for the development of novel sustainable products. The main structural component of wood is cellulose, which, in turn, is the feedstock of nanocellulose, one of the most explored nanomaterials. Different applications of nanocellulose have been proposed, including packaging, functional coatings, insulating materials, nanocomposite fields among others. However, the intrinsic flammability of nanocellulose restricts its use in some industries where fire risk is a concern. This paper overviews the most recent studies of the fire resistance of nanocellulose-based materials, focusing on thin films, coatings and aerogels. Along with effectiveness, increased attention to sustainable approaches is considered in developing novel fire-resistant coatings. The great potential of bio-based fire-resistant materials, combined with conventional non-halogenated fire retardants FRs, has been established. The formulation methods, types of fire retardants and their action modes, and methods used for analysing fire retardancy are discussed in the frame of this overview.

Helicobacter pylori is a gastric oncopathogen that infects over half of the world’s human population. It is a Gram-negative, microaerophilic, helix-shaped bacterium that is equipped with flagella, which provide high motility. Colonization of the stomach is asymptomatic in up to 90% of people but is a recognized risk factor for developing various gastric disorders such as gastric ulcers, gastric cancer and gastritis. Invasion of the human stomach occurs via numerous virulence factors such as CagA and VacA. Similarly, outer membrane proteins (OMPs) play an important role in H. pylori pathogenicity as a means to adapt to the epithelial environment and thereby facilitate infection. While some OMPs are porins, others are adhesins. The epithelial cell receptors SabA, BabA, AlpA, OipA, HopQ and HopZ have been extensively researched to evaluate their epidemiology, structure, role and genes. Moreover, numerous studies have been performed to seek to understand the complex relationship between these factors and gastric diseases. Associations exist between different H. pylori virulence factors, the co-expression of which appears to boost pathogenicity of the bacterium. Improved knowledge of OMPs is a major step towards combatting this global disease. Here, we provide a current overview of different H. pylori OMPs and discuss their pathogenicity, epidemiology and correlation with various gastric diseases.

Lifestyle health has been recognized as an evidence-based innovation that defines how daily habits and practices impact both the prevention and treatment of disease and provides an important adjunctive component to overall health. Specifically, an approach with small changes over time can have a dramatic impact on the health and well-being of individuals not only, in general, but also can be applied to skin health. However, lifestyle health factors to improve skin well-being have not been discussed extensively and/or well promulgated. The narrative for this overview focuses on providing a summary for topic background information, but more importantly, presents four lifestyle factors that can improve dermal health [i.e., factor 1: nutrition - diet; factor 2: rest (sleep); factor 3: movement/physical exercise, and factor 4: social and community associations]. This was accomplished by identifying previous journal articles and reviews with emphasis over the last five years (from January 2018 through July 2023; 156 out of 190 references cited or 82 %) using scientific search databases. The main conclusions of this overview encourage the concept that lifestyle health factors such as nutrition/diet, rest/sleep, movement/physical exercise, and community/social interactions support enhanced skin health and well-being with aging. Plus, social media interventions that aim to promote dietary, sleep and physical activity changes might be an application to improve skin health in the future.

Histone post-translational modification is one of the main mechanisms of epigenetic regulation, which plays a crucial role in the control of gene expression and various biological processes. However, whether or not it affects fungal virulence is not clear in Sclerotinia sclerotiorum. In this study, we identified and cloned the histone methyltransferase Defective in methylation 5 (Dim5) in S. sclerotiorum, which encodes a protein containing a typical SET domain. SsDim5 was found to be dynamically expressed during infection. Knockout experiment demonstrated that deletion of SsDim5 reduced the virulence in Ssdim5-1/Ssdim5-2 mutant strains, accompanied by a significant decrease in H3K9 trimethylation levels. Transcriptomic analysis further revealed the downregulation of genes associated with mycotoxins biosynthesis in SsDim5 deletion mutants. Additionally, the absence of SsDim5 affected the fungus's response to oxidative and osmotic, as well as cellular integrity. Together, our results indicate that the H3K9 methyltransferase SsDim5 is essential for H3K9 trimethylation, which regulating fungal virulence to host plants through impacting on mycotoxins biosynthesis, and the response to environmental stresses in S. sclerotiorum.

Cryptococcus neoformans is a pathogenic fungus that causes cryptococcosis, a significant secondary infection in immunocompromised individuals with immune-suppressive related symptoms from HIV infection and organ transplants. Fungaemia occurs via the respiratory route and spreads by tissue invasion into other body parts. Enzymes and membrane-associated permeases/transporters are accessory proteins deployed to enhance the survival, adaptation, and infection caused by Cryptococcus species. The nutrient bioavailability determines the functional turnover rate of these proteins in the immediate fungal environment. Low oxygen levels in the internal organs, essential micro-elements locked in the storage proteins, catabolite repression, phagolysosomal low glucose level and pH, tight junction, and extracellular matrixes are challenges to the survival of this pathogen in the host. This review identifies key hydrolytic and metabolic enzymes and permeases/transporters as essential weapons of virulence in addition to survival, tolerance, resistance, adaptation, and infection in humans. Under the regulation of different transcription factors, these proteins are released in response to nutrient sensors designed to siphon the host nutrients and induce infection in predisposed individuals. The extracellular secretory vesicles called “exosomal virulence bag” also harbour cryptococcal urease, laccase, phosphatase, and capsular components as additional secretory protein weapons for immune evasion, tissue invasion and persistence.

Periodontitis is a chronic inflammatory disease affecting the tissues that surround and support the teeth. In the U. S., approximately 65 million people are affected by this condition. Its occurrence is also associated with many important systemic diseases such as cardiovascular disease, rheumatoid arthritis, and Alzheimer’s disease. Among the most important etiologies of periodontitis is Porphyromonas gingivalis, a keystone bacterial pathogen. Keystone pathogens can orchestrate inflammatory disease by remodeling a normally benign microbiota causing imbalance between normal and pathogenic microbiota (dysbiosis). The important characteristics of P. gingivalis causing dysbiosis are its virulence factors that cause effective subversion of host defenses to its advantage [1], allowing other pathogens to grow. However, the mechanisms involving these processes are poorly understood. However, various microbial strategies target host sialoglycoproteins for immune dysregulation. In addition, the enzymes that break down sialoglycoproteins/sialoglycans are the “sialoglycoproteases”, resulting in exposed terminal sialic acid. This process could lead to pathogen-toll like receptor (TLR) interactions mediated through sialic acid receptor–ligand mechanisms. By assessing the function of P. gingivalis sialoglycoproteases, could pave the way to designing carbohydrate analogues and sialic acid mimetics to serve as drug targets.

A large core size and bending resistance are very important properties of mid-infrared energy transfer fibers, but large core sizes usually lead to a deterioration of bending properties. A negative-curvature nested node-free anti-resonant hollow-core fiber (AR-HCF) based on quartz is proposed. It was made by adding a nested layer to a previous AR-HCF design to provide an additional anti-resonance region while keeping the gap between adjacent tubes strictly correlated to the core diameter to produce a node-free structure. These features improve the fiber’s bending resistance while achieving a larger core diameter. The simulation results show that the radial air-glass anti-resonant layer is increased by the introduction of the nested anti-resonant tube, and the weak interference overlap between the fiber core and the cladding mode is reduced, so the fiber core’s limiting loss and the sensitivity to bending are effectively reduced. When the capillary wall thickness t of the fiber is 0.71 μm, the core diameter D is 70 μm, the ratio of the inner diameter of the cladding capillary to the core diameter d/D is 0.62, and the diameter of the nested tube is d0=29 μm, the fiber has a lower limiting loss at the wavelength of 2.79 μm, and the limiting loss is 3.28×10-4 dB/m. At the same time, the optimized structure also has good bending resistance. When the bending radius is 30 mm, the bending loss is only 4.72×10-2 dB/m. To our knowledge, this is the first research to achieve an anti-bending low-loss micro-structure hollow fiber with a bending radius of less than 30 mm in the 2.79 μm band. An anti-bending low-loss anti-resonant hollow-core fiber with this structure constitutes a reliable choice for the light guiding system of a 2.79 μm band erbium laser therapy instrument.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

In order to tackle the issue of severe rocking phenomenon under seismic conditions in structures equipped with steel spring isolation bearings, this paper investigates a novel type of anti-rocking bearing. Firstly, the structural configuration and working principle of the novel anti-rocking bearing are introduced, and a design method for bearing parameters is proposed. Secondly, a finite element analysis model is established using SAP2000 software to conduct nonlinear dynamic time history analysis under seismic loading. The analysis results show that the structural arrangement of the novel anti-rocking bearing reduces both the vertical displacement difference and the rocking angle of the isolation layer. The bearing exhibits a certain level of anti-rocking effect, but it may cause significant tensile forces in some bearings, necessitating the installation of anti-tensile reinforcement. The effectiveness of the anti-rocking effect improves as the stiffness of the steel tension rod in the bearing increases; however, it also leads to higher maximum tension in individual bearings as well as the total tension in all bearings. For structures equipped with the novel anti-rocking bearing, the acceleration amplifies under most cases, with amplification coefficients ranging from 0.82 to 1.55. The performance of the novel anti-rocking bearing varies significantly for different seismic waves. The stiffness of the steel tension rod should be determined considering the reference pressure of the bearing and the maximum designed tension of the bearing. Through the finite element simulation of the bearing, the mechanical properties of the bearing are basically the same as the theoretical analysis results. For the cylinder and the joint bearing, certain structural measures need to be taken to ensure its strength and stiffness.

Elemental sulfur, commonly known for its wide range of biological activity, has a long history of being used to protect all garden and vegetable crops from a range of pests and diseases, including powdery mildew, ascochyta blight, clubroot, plant mites, oidium, anthracnose, and scab. In the present study, a quick and environmentally friendly approach has been developed for the synthesis of sulfur nanoparticles with antibacterial activity. Sulfur nanoparticles (SNPs) were prepared by modifying the surface of elemental sulfur using various polyelectrolyte-surfactant mixtures (PSM) including NaCMC-SDBS and PHMG-CTAB. The SNPs were characterized by UV–visible spectrophotometry, X-ray diffraction (XRD), and thermogravimetric analysis (TG/DSC), scanning electron microscopy (SEM), with the SNPs showing an almost spherical shape with an average size in the range of 150-200 nm. The antibacterial activity of the sulfur nanoparticles was tested using against gram-positive S. aureus and E. faecium and gram-negative E. coli and P. aeruginosa bacteria. From this, it could be seen that SNPs exhibited significant antimicrobial activity against gram-positive bacteria, i.e., S. aureus and E. faecium. The in vitro cytotoxicity of the SNPs-1 and SNPs-2 studied to normal (MeT-5A) and tumorous (MCF-7) human cell lines was assessed in the concentration range from 500 μg/ml to 0.12 mg/ml, from which it was determined as being non-cytotoxic. The received products can be considered for potential application in agriculture and medicine.

Members of the genus Mycoplasma and related organisms impose a substantial burden of infectious diseases on humans and animals, but the last comprehensive review of mycoplasmal pathogenicity was published 20 years ago. Post-genomic analyses have now begun to support the discovery and detailed molecular biological characterization of a number of specific mycoplasmal virulence factors. This review covers three categories of defined mycoplasmal virulence effectors: 1) specific macromolecules including the superantigen MAM, the ADP-ribosylating CARDS toxin, sialidase, cytotoxic nucleases, cell-activating diacylated lipopeptides, and phosphocholine-containing glycoglycerolipids; 2) the small molecule effectors hydrogen peroxide, hydrogen sulfide, and ammonia; and 3) several putative mycoplasmal orthologs of virulence effectors documented in other bacteria. Understanding such effectors and their mechanisms of action at the molecular level connects the biology of the bacteria to direct effects on the host and host responses they elicit, and is expected to translate into new interventions for human and veterinary mycoplasmosis.

Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process.

Sepsis is a serious disease that can lead to mortality. The etiology of the disease is connected to how the body as a host reacts toward microbes such as bacteria, viruses, and fungi invasion. Current research shows that during sepsis, the reaction toward microbe attacks takes two main phases. The first is known as a cytokine storm, while the second is a vicious cycle of pro-inflammatory responses followed by a strict anti-inflammatory response led by CD4+ Tregs. Various immunomodulatory therapies have been proposed to break the cycle of pro- and anti-inflammatory reactions to sepsis. However, clinical trials did not show promising results, indicating further research into the mechanism that Treg uses to inhibit proinflammatory reactions. We used next-generation sequencing (NGS) analysis of bulk RNA-seq and single-cell RNA-seq data to examine the exact molecular pathways used by Treg to inhibit the immune response in sepsis. Our approach identified ACOD1 (Aconitate Decarboxylase 1) as a primary mediator of Treg suppression of immune cells. We identified and validated CD36 as a downstream target of ACOD1. CD36 is a known metabolite regulator in Tregs. Taken together, our results indicate that targeting ACOD1 could prove valuable in regulating Treg function during sepsis.

Metallo-β-lactamases (MBLs) are members of the structurally conserved but functionally diverse MBL-fold superfamily of metallohydrolases. MBLs are a major concern for global health care as they efficiently inactivate β-lactam antibiotics, including the “last-resort” carbapenems, and no clinically suitable inhibitors are currently available. Increasingly, promiscuous β-lactamase activity is also observed in other members of the superfamily, including from viruses, which represents an underexplored reservoir for future pathways to antibiotic resistance. Here, two such MBL-fold enzymes from Bacillus phages, the cyclic mononucleotide-degrading proteins ApycGoe3 and ApycGrass, are shown to efficiently degrade β-lactam substrates in vitro. In particular, ApycGrass displays a distinct preference for carbapenem substrates with a catalytic efficiency that is within one order of magnitude of that of the clinically relevant MBL NDM-1. Mutagenesis experiments also demonstrate that the loss of a metal-bridging aspartate residue reduces nuclease activity up to 35-fold, but improves carbapenemase activity. In addition, we propose that the oligomeric state significantly influences β-lactamase activity by modifying access to the active site pocket. Together, these observations hint at a possible new avenue of resistance via the spread of phage-borne MBL-fold enzymes with β-lactamase activity.

Toll-like receptor 4 (TLR4) is a member of the TLR family. Members of the TLR family play an important role in innate immune responses and are induced by recognition of pathogen-associated molecular patterns. They are also involved in cell proliferation and apoptosis in cancer. We investigated the role of TLR4 in apoptotic cell death in gynecological cancer cells; gynecological cancer is associated with infertility and spontaneous abortion. To examine the effect of TLR4 activation on apoptotic signaling in cancer cells, cultured primary cancer cells were treated with the TLR4 agonist lipopolysaccharide (LPS). The morphology of cancer cells was compared with normal myometrial cells. Enhanced growth rate and loss of contact inhibition with cellular overlap was observed in the cancer cells. The molecular mechanism analysis revealed differential expression of tumor suppressor genes in LPS-treated cancer cells. The expression of apoptosis-related caspase-3 was increased significantly in cancer cells with TLR4 activation after exposure to LPS. Taken together, these results suggest the pro-apoptotic activity of TLR4 as a potential therapeutic target for the treatment of gynecological cancers.

African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injure the pork product and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression, but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and host immune system, along with the involvement of virulence related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, NF-κB, JAK/STAT, apoptosis, and other modulation. The aim is to summarize the dynamic process during the ASFV infection and entry into host cell, provide a rational insight into development of vaccine and a better clear knowledge of how ASFV impacts host.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Fragile X syndrome (FXS) is the most frequent monogenic form of autism spectrum disorder (ASD). Autistic FXS is caused by loss of the fmr1 gene product, the fragile X mental retardation protein (FMRP), triggering physiological and behavioral abnormalities. It is correlated with clock components for behavioral circadian rhythm. Mutation of this gene causes the disturbances in sleep patterns and circadian behavior commonly observed in patients with autistic FXS, accompanied by frequent dysregulation of melatonin synthesis and melatonin-dependent signaling. These changes impair vigilance, learning and memory, and are also linked to autistic behavior including the abnormal anxiety response. However, although several possible causes, symptoms, and clinical features of ASD have been investigated, the correlation between an altered circadian rhythm and autistic FXS has not been extensively studied. Recent works have highlighted the impact of melatonin on the nervous, immune, and metabolic systems. Even though utilization of melatonin for sleep disorder in ASD has been considered in clinical research, further studies should be aimed at its neuroprotective role in ASD during developmental period. In this review, we focus on the regulatory circuits involved in melatonin dysregulation and circadian system disruption in those with autistic FXS. Additionally, we discuss the neuroprotective effect of melatonin intervention. This may improve neuroplasticity and physical capability. We also review the underlying molecular mechanisms, and suggest that melatonin may be a useful novel treatment for autistic FXS, countering the adverse effects of circadian variation.

Ice accumulation poses considerable challenges in transportation, notably in the domain of general aviation. The present study combines the strengths and limitations of conventional aircraft de-icing techniques with the emerging trend toward all-electric aircraft. The study aims to utilize laser-induced graphene (LIG) technology to create a multifunctional surface, seamlessly integrating hydrophobic properties with efficient electrical heating to mitigate surface icing effectively. We investigated the utilization of a 10.6 μm CO2 laser for direct writing on polyimide (PI), a widely-used insulating encapsulation material. From the thermomechanical perspective, our initial analysis using COMSOL Multiphysics software revealed that when the laser power P exceeds 5 W, the PI substrate experience ablative damage. The experimental results show that when P ≤ 5W, an increase in power has a positive impact on the quality, surface porosity, roughness reduction, line-spacing reduction, and water contact-angle enhancement of the graphene. Conversely, when P > 5 W, higher power negatively affects both the substrate and the graphene structure by inducing excessive ablation. However, it influences the graphene line height positively and is consistent with overall experimental-simulation congruence. Furthermore, the incorporation of high-quality graphene resulted in a surface that exhibited higher contact angles (CA > 120°), lower energy consumption, and higher heating efficiency compared to the use of traditional electrically heated materials for anti-icing applications. The potential applications of this one-step fabrication method extend across various industries, particularly aviation, marine engineering, and other ice-prone domains. Moreover, the method has extensive prospects for addressing pivotal challenges associated with ice formation and serves an innovative and efficient anti-icing technology.

The field of microbial pathogenesis seeks to identify the agents and mechanisms responsible for disease causation. Since Robert Koch introduced postulates that were used to guide the characterization of microbial pathogens, technological advances have substantially increased the capacity to rapidly identify a causative infectious agent. Research efforts currently focus on causation at the molecular level with a search for virulence factors (VFs) that contribute to different stages of the infectious process. We note that the quest to identify and characterize VFs sometimes lacks scientific rigor, and this suggests a need to examine the epistemology of VF characterization. We took this premise as an opportunity to explore the epistemology of VF characterization. In this perspective, we discuss how the characterization of various gene products that evolved to facilitate bacterial survival in the broader environment have potentially been prematurely mischaracterized as VFs that contribute to pathogenesis in the context of human biology. Examples of the reasoning that can affect misinterpretation, or at least premature assignment of mechanistic causation, are provided. Our aim is to refine categorization of VFs by emphasizing a broader biological view of their origin.

In this work, we analysed human isolates of nontyphoidal Salmonella enterica subsp. enterica (NTS), which were collected from salmonellosis cases in Armenia from 1996 to 2019. This disease became a leading food-borne bacterial infection in the region, with the younger age groups especially affected. The isolates were characterised by serotyping, Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR) typing, and whole genome sequencing (WGS). The main serotypes were S. Typhimurium, S. Enteritidis, and S. Arizonae. ERIC-PCR indicated a high degree of clonality among S. Typhimurium strains, which were also multidrug-resistant and produced extended spectrum beta-lactamases. During the study period, the frequency of S. Typhimurium and S. Arizonae isolations were decreasing, but with the increase of S. Enteritidis and other NTS. A total of 42 NTS isolates were subjected to WGS and explored for virulence-related traits and the corresponding genetic elements. Some virulence and genetic factors were shared by all NTS serotypes, while the main differences were attributed to the serotype-specific diversity of virulence genes, SPIs, virulence plasmids, and phages. The results indicated the variability and dynamics in the epidemiology of salmonellosis and a high virulence potential of human NTS isolates circulating in the region.

Food waste is a common issue arising from grinding of food by experimental animals, leading to excessive food scraps falling into cages. In the wild, animals grind food by gnawing vegetation and seeds, potentially damaging the ecological environment. However, limited ecology studies have focused on food grinding behavior since the last century, with even fewer on rodent food grinding, particularly recently. Although food grinding function is partially understood, biological purposes remain under-investigated and driving factors unclear. This review aims to explain potential causes of animal food grinding, identify influencing factors, and discuss contexts and limitations. Specifically, we emphasize recent progress on gut microbiota significance for food grinding. Moreover, we show abnormal food grinding is determined by degree of excess normal behavior, emphasizing food grinding is not meaningless. Findings from this review promote comprehensive research on the myriad factors, multifaceted roles, and intricate evolution underlying food grinding behavior, benefiting laboratory animal husbandry and ecological environment protection, and identifying potential physiological benefits yet undiscovered.

Antimicrobial application of carbon nanomaterials such as carbon nanotubes (CNTs), capped CNT, C60 fullerene, and C70 fullerene are increasing owing to their low cytotoxicity properties compared to other nanomaterials such as metallic nanoparticles. Enhanced mechanical property and antibacterial activity can be caused by incorporation of CNTs in 3-dimentional (3D) printed nanocomposites (NCs). Interruption of bacterial membrane resulting from cylindrical shape and high aspect ratio properties has been found as the prominent antibacterial mechanism of CNTs. However, unraveling interaction of CNT, capped CNT, C60 fullerene, and C70 fullerene with virulence factors of the main bacterial pathogenesis has not yet been known. Therefore, in the present study, interactions of CNT, capped CNT, C60, and C70 with the eight virulence factors including protein kinase A and ESX-secreted protein B of Mycobacterium tuberculosis, pseudomonas elastase and exotoxin A of Pseudomonas aeruginosa, alpha-hemolysin and penicillin binding protein 2a of Staphylococcus aureus and shiga toxin 2a and heat-labile enterotoxin of Escherichia coli have been evaluated by molecular docking method of AutoDock Vina. This study disclosed the binding strength followed the sequence CNT > capped CNT > C70 > C60 towards alpha-hemolysin of S. aureus compared to other virulence factors with values of -19.6, -18.8, -13.6, and -12.8 kcal/mol, respectively. The lowest and highest binding affinity were found for CNT against 1TII and 1MWT by binding energy values of 97.4 and -20.1 kcal/mol. The stability of CNT-1MWT complex at the different times has resulted according to the normal mode analysis of elNémo and iMOD servers. Future studies should be focused on improving cellular uptake of CNTs, capped CNTs, C70, and C60 by surface functionalization for active targeting of bacteria.

Currently, in some domestic and foreign mines, the backfill drilling pipeline experience a rupture phenomenon even when the wear degree is low. This results in a delay in production due to the filling becoming 'sick'. This paper presents, for the first time, the damage mechanism from a mechanical perspective and re-derives the anti-extrusion strength model of the backfill drilling pipeline. We investigate the influence of law on the anti-extrusion strength of pipelines from the perspective of stratum and cement ring. We then verify the theoretical and simulation results through engineering examples. The results demonstrate that the Mises stress criterion is a suitable modification principle for the anti-extrusion strength model of the backfill drilling pipeline. The anti-extrusion strength of the pipeline is related to the elastic modulus and Poisson's ratio of the stratum, and the thickness of the cement ring. It is negatively affected by the depth of the stratum. For hard strata, a cement ring with a smaller elastic modulus is suitable, while for soft stratum, a cement ring with a larger elastic modulus is recommended. When the missing angle of the cement ring is less than 60°, the stress concentration factor increases up to 2.2. The stress unloading capacity of the cement ring ranges from 32.7% to 37.8%, and optimal performance of the cement ring is achieved when it has high strength and low rigidity. The backfill filling pipeline of a copper mine abroad was destroyed due to external extrusion force exceeding its anti-extrusion strength value. The modified pipeline anti-extrusion strength model is 18.2% higher than the casing API strength value. This finding can inform the design of the backfill filling pipeline for China's kilometer-deep wells in the future.

Background: We aimed to identify overexpressed genes or related pathways associated with good responses to anti-HER2 therapy and to suggest a model for predicting drug response in neoadjuvant therapy with trastuzumab in HER2-positive breast cancer patients. Methods: We recruited 64 women with breast cancer and categorized them into three groups according to anti-HER2 therapy response. RNA from twenty core needle biopsy paraffin-embedded tissues and four cultured cell was extracted, reverse transcribed, and subjected to microarray. The obtained data were analyzed using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and database for annotation, visualization, and integrated discovery. Results: In total, 6,656 genes differentially expressed between trastuzumab-susceptible and trastuzumab-resistant cell lines (3,224 upregulated and 3,432 downregulated). Expression changes in 34 genes in several pathways were found to be related to the response to trastuzumab-containing treatment, interfering with adhesion to other cells or tissues (focal adhesion) and regulating extracellular matrix interactions and phagosome action. Thus, decreased tumor invasiveness and enhanced drug effects might be the mechanisms explaining the better drug response in complete response group. Conclusions: This multigene assay-based study provides insights into breast cancer signal transduction and the possible prediction of treatment response to targeted therapies such as trastuzumab.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

Tuberculosis (TB) remains a global health threat, necessitating innovative strategies for control and prevention. This comprehensive review explores the Mycobacterium tuberculosis Lysine Exporter (LysE) gene, unveiling its multifaceted roles and potential uses in controlling and preventing tuberculosis (TB). As a pivotal player in eliminating excess L-lysine and L-arginine, LysE contributes to the survival and virulence of M. tuberculosis. This review synthesizes findings from different electronic databases and includes 13 studies focused on the LysE of M. tuberculosis. The research unveils that LysE can be a potential drug target, a diagnostic marker for TB, and a promising candidate for vaccine development. The absence of LysE in the widely used BCG vaccine underscores its uniqueness and positions it as a novel area for TB prevention. In conclusion, this review underscores the significance of LysE in TB pathogenesis and its potential as a drug target, diagnostic marker, and vaccine candidate. The multifaceted nature of LysE positions it at the forefront of innovative approaches to combat TB, calling for sustained research efforts to harness its full potential in the global fight against this infectious disease.

Background: On Dec 19, 2019, the public health department of China reported that an outbreak of pneumonia was caused by a novel Coronavirus. The virulence of the new virus COVID-19 was much greater than either the SARs and MERSs viruses and on March 11, 2020, the World Health Department (WHO) declared a worldwide pandemic. Understanding the pathophysiology of virulence of the SARS-COV-2 virus is absolutely necessary for understanding the transmission, virulence factors, reduce risk factors, clinical presentation, predict outcomes of the disease and provide guidance for any current or future treatment protocols. Methodology: A comprehensive PubMed search was performed during December 20, 2019 and April 03, 2020, utilizing the words: Wuhan Virus, COVID-19, SARs coronavirus, ACE2, S-protein, virulence, clinical presentation, epidemiology, genome, treatment, structure, MERs, pathogenesis and/or pathology alone and in combination with other terms. Each paper was evaluated by three content experts for quality, reproducibility, credibility and reputation of the journal. Results: The SARS-COV-2 virus is much more virulent than either the SAR’s or MER’s virus and its ability to cause serious disease inversely corresponds to the person’s ability to produce T-cells which declines linearly with age. The ACE2 receptor binding site does not vary among different ethnic groups but do in ACE-2 expression levels. This variance in expression level may explain for different infectivity rates among men and women and predict and explain different susceptibilities to infection by different ethnic groups. Furthermore, by understanding the underlying pathophysiology one can explain and provide guidance to the clinical effectiveness of any treatment. Conclusions: The underlying pathophysiology of COVID-19 explains not only the virulence, and clinical presentation, but, explains at a molecular level the comorbidity risk factors such as hypertension, sex, and age. Ethnic and anatomic expression patterns of ACE-2 and associated pathophysiology suggests that Native Americans and Asians may be particularly susceptible to this disease.

This study uses machine learning to identify key factors influencing the cost-effectiveness of over-the-counter (OTC) medications. By developing a novel cost-effectiveness rating (CER) from user ratings and prices, we analyzed data from Amazon. The findings indicate that FSA/HSA eligibility, symptom treatment range, safety warnings, special effects, active ingredients, and packaging size significantly impact cost-effectiveness across cold, allergy, digestion, and pain relief medications. Medications eligible for FSA or HSA funds, treating a broader range of symptoms, and having smaller packaging are perceived as more cost-effective. Cold medicines with safety warnings were found to be cost-effective due to their lower average price and effective ingredients like phenylephrine and acetaminophen. Allergy medications with kid-friendly features showed higher cost-effectiveness, and ingredients like calcium, famotidine, and magnesium boosted the cost-effectiveness of digestion medicines. These insights help consumers make informed purchasing decisions and assist manufacturers and retailers in enhancing product competitiveness. Overall, this research supports better decision-making in the pharmaceutical industry by highlighting factors that drive cost-effective medication purchases.

The review explores the therapeutic potential of mangrove plants as sources of bioactive compounds, particularly focusing on their anti-inflammatory properties. Mangroves, found in tropical and sub-tropical tidal coasts, exhibit unique ecological and biological activities. The review compiles and examines 136 research findings published between 1982 and 2018, with 41 studies specifically addressing the anti-inflammatory properties of mangroves in Indian coastal regions, including the Andaman and Nicobar Islands. It summarizes the chemical structures, molecular weights, formulas, solvents, and biological activities of these mangroves, as reported by various researchers over time. The data underscore the significant potential of tropical Indian mangroves in anti-inflammatory applications. However, a notable research gap exists regarding the extraction of bioactive compounds from mangrove species in the Andaman and Nicobar Islands compared to other regions such as Gujarat, Maharashtra, Goa, Karnataka, Kerala, Tamil Nadu, Andhra Pradesh, Odisha, West Bengal, and Puducherry. Overall, the compilation provides valuable insights into mangrove-based studies for drug discovery research, emphasizing the need for further exploration and exploitation of these natural resources.

Cervical cancer is one of the ailments that endangers the health of women all over the world and causes infertility. Fortunately, this disease can be avoided. Both the results and participation rates of the current preventative strategy remain poor. Hence, preventative or early detection methods remain challenging and open. In gynecology and computer science fields, few studies on identifying cervical cancer are based on behavior risk factor and machine learning. Moreover, various social and behavioral aspects might often make it more difficult to detect cervical cancer especially in low‑ and middle‑income countries (LMICs). Accordingly, focus on predicting the presence of cervical cancer through behavioral risk factors is the basic structure of this research. We proposed an approach to classify cervical cancer from a social-behavioral perspective using logistic regression to predict cervical cancer. We got significantly improved outcomes than the existing methods. Moreover, we used feature engineering to formulate less dimensionality as a pre-processing step and optimized parameters to be prepared for classification phase. The results proved that using the logistic regression with regularization type L1 had a promising performance. The accuracy of Logistic Regression (LR) L1 was 97.2%. Such results support the proposed work as a reliable classification predictive tool.

Background: Interleukins play dual roles in breast cancer, acting as both promoters and inhibitors of tumorigenesis within the tumor microenvironment, which is shaped by their inflammatory functions. This study analyzed the subtype-specific prognostic significance of anti-inflammatory and pro-inflammatory signatures using microarray-based gene ex-pression analysis. Correlations between these interleukin signatures and immune cell markers (CD8, IgKC, CD20) and immune checkpoints (PD-1) were also evaluated. Materials and Methods: The study investigated the prognostic significance of an an-ti-inflammatory interleukin signature (IL-12, IL-21, IFN-γ) and a pro-inflammatory inter-leukin signature (IL-4, IL-5, IL-10, IL-13, IL-17, CXCL1) for metastasis-free survival (MFS) using Kaplan-Meier curves and Cox regression analyses in a cohort of 461 patients with early breast cancer. Correlations were analyzed using the Spearman-Rho correlation coef-ficient. Results: Kaplan-Meier curves revealed that the prognostic significance of the an-ti-inflammatory signature was specifically pronounced in the basal-like subtype (p=0.004, Log Rank). This signature retained independent prognostic significance in multivariate Cox regression analysis (HR 0.463, 95% CI 0.290-0.741; p=0.001). Higher expression of the anti-inflammatory interleukin signature was associated with longer MFS. The pro-inflammatory interleukin signature showed a significant prognostic effect in the whole cohort, with higher expression associated with shorter MFS (p=0.034). Strong cor-relations were found between the anti-inflammatory signature and CD8 expression (ρ=0.391; p

As a precious natural resource, forests are being destroyed. In previous studies, there is a lack of interactive assessment of its distribution that comprehensively considers multiple external disturbances. This paper takes the Barcelona Metropolitan Region as an example. Based on remote sensing, it analyzes the development process of the forest from 2006 to 2018 through multiple landscape indicators, and OLS models were established to analyze variables that have direct and indirect effects on forest distribution. In addition, the ecological structure of the forest was analyzed based on NDVI. It was found that the forest area is the largest but has been decreasing, becoming more complex in distribution structure. Much of the forest was converted to agricultural land and grassland. The green quality of forests was increasing, and the broad-leaved forest, the second largest area, contributes the most. NDVI is the most important positively correlated variable, and daytime surface temperature is an important inverse factor related to NDVI. In addition, NDBI is also a negative condition that inhibits forest development. In conclusion: The BMR forest area is decreasing and becoming more fragmented. NDVI and daytime LST are the two most significant factors. Climate warming may lead to worse forest development.

In Italy HPV vaccination was implemented for girls since 2007 but its coverage was lower than recommended level. Sicily is one of the Italian administrative regions with lower vaccination coverage, ranging in the birth cohorts 1996–1999 from 59% to 62%. Aim of the study was to investigate factors associated with refusal of anti-HPV vaccination among young adult women of Palermo, Italy. A cross-sectional study was conducted through the administration of a telephone questionnaire, consisting of 23 items on HPV infection and vaccination knowledge based on Health Belief Model framework. The eligible population were young women with at least a previous vaccination among all included in Sicilian Vaccination schedule, without starting or completing anti-HPV vaccination schedule. Overall, 141 young women were enrolled, of them 84.4% were unvaccinated and 15.6% had at least one dose of HPV vaccine. In multivariate analysis, factors associated with the failure to perform the HPV vaccination were degree as school level (OR = 10.2, p = 0.041), lower participation at school seminar on HPV (OR = 0.2, p = 0.047) and lower perception of anti-HPV vaccine benefits (OR = 0.4, p = 0.048). Public health educational program focusing and tailored on benefits perception of anti-HPV vaccine and HPV disease severity, especially if carried out at school, can improve HPV vaccination uptake.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

In this follow-up study, we aimed to assess the effectiveness of the “I do not smoke, I exercise”, anti-smoking preventive health education program. The program was based on the Theory of Planned Behavior supplemented with life-skills teaching and targeted at high school students. The intervention comprised ten one-hour online sessions, administered by physical education instructors. The study cohort comprised 222 students (109 boys, 113 girls) from 11 secondary schools, with an average age of 16.42 ± 1.36 years. Data collection involved pre- and post-intervention self-assessment questionnaires. The examined variables included attitudes towards smoking, intention to smoke, subjective norm, perceived behavioral control (PBC), knowledge about smoking, smoking behavior, exercise behavior, attitudes toward the program's implementation, and satisfaction with the program. Separate paired samples t-test revealed a significant improvement in students' knowledge about smoking, perceived behavioral control, and overall program satisfaction following the intervention. However, no significant changes were observed in the remaining variables. These findings suggest that the health education smoking prevention intervention incorporates techniques and strategies that influence the Perceived Behavioral Control variable, emphasizing students' strong interest in educationally theorized programs integrating technology into their design. Future studies should consider further examination of tobacco control strategies within the high school context.

Objective: This research was aimed to estimate the anti-fatigue effects of arecoline and elucidate its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL/6 mice were randomly allocated into six groups: a control group, a SD-induced fatigue model group, a group receiving Rhodiola Rosea capsules (2.5 mg/kg), and arecoline groups administered low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on the mouse fatigue-related behaviors was assessed by the behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. Enzyme-linked immunosorbent assays (ELISAs) were utilized to measure the levels of the relevant biochemical markers. Western blotting was employed to quantify the expression of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline significantly reduced both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased serum levels of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol, while elevated total testosterone, lactate dehydrogenase, and immunoglobulin G levels. Furthermore, it significantly increased superoxide dismutase(SOD), catalase(CAT), and glutathione peroxidase activity in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels were significantly increased, cytokine levels were markedly reduced, and the expression of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissue was significantly upregulated. Conclusion: The current study for the first time demonstrated that arecoline has significant anti-fatigue activity, and its mechanism of action is related to elevate the levels of glucose and lipid metabolism, relieve oxidative stress damage, inhibit neuroinflammatory response, regulate neurotransmitter levels and Keap1/Nrf2/HO-1 signaling pathway. The current study provides a new insight into the potential of arecoline in prevention and improvement of fatigue.

White Spot Syndrome Virus (WSSV) has emerged as one of the most prevalent and lethal viruses globally, and infects both shrimps and crabs in the aquatic environment. This study aimed to investigate the occurrence of WSSV in different ghers of Bangladesh and the virulence of the circulating phylotypes. We collected 360 shrimp (Penaeus monodon) and 120 crab (Scylla sp.) samples from the South-East (Cox’s Bazar) and South-West (Satkhira) coastal regions of Bangladesh. The VP28 gene-specific PCR assays and sequencing revealed statistically significant (p < 0.05, Kruskal Wallis test) differences in the prevalence of WSSV in shrimps and crabs between the study areas (Cox’s Bazar and Satkhira), and over the study periods (2017-2019). The mean Log load of WSSV varied from 8.40 (Cox’s Bazar) to 10.48 (Satkhira) per gram of tissue. The mean values for salinity, dissolved oxygen, temperature and pH were 14.71±0.76 ppt, 3.7±0.1 ppm, 34.11±0.38˚C and 8.23±0.38, respectively in the WSSV-positive ghers. The VP28 gene-based phylogenetic analysis showed an amino-acid substitution (E→G) at 167th position in the isolates from Cox’s Bazar (referred to as phylotype BD2) compared to the globally circulating one (BD1). Shrimp PL artificially challenged with BD1 and BD2 phylotypes with filtrates of tissue containing 0.423 X 109 copies of WSSV per mL resulted a median LT50 value of 73 hrs and 75 hrs, respectively. The in-vivo trial showed higher mean Log WSSV copies (6.47±2.07 per mg tissue) in BD1 challenged shrimp PL compared to BD2 (4.75±0.35 per mg tissue). Crabs infected with BD1 and BD2 showed 100% mortality within 48 hrs and 62 hrs of challenge, respectively with mean Log WSSV copies of 12.06±0.48 and 9.95±0.37 per gram tissue, respectively. Moreover, shrimp antimicrobial peptides (AMPs) penaeidin and lysozyme expression was lower in BD1 challenged group compared to BD2 challenged shrimps. These results collectively demonstrated that relative virulence properties of WSSV based on mortality rate, viral load and expression of host immune genes in artificially infected shrimp PL could be affected by single aa substitution in VP28.

The quest for youthful, healthy skin and full, vibrant hair has long been a driving force in the dermocosmetics field. However, traditional approaches often struggle to address the underlying causes of aging, damage, and hair loss. Regenerative cosmetics, powered by skin tissue engineering, offer a transformative alternative. This review explores the emerging field of using engineered skin tissues for cosmetic purposes, focusing specifically on their potential for anti-aging, repair, and hair restoration applications. We discuss how these technologies aim to rejuvenate aging skin by promoting collagen production, reducing wrinkles, and improving overall skin function. Additionally, the use of engineered skin for wound healing and scar reduction is examined, highlighting their potential to improve the appearance and functionality of damaged skin. Finally, we advance the exciting prospects of utilizing skin tissue engineering techniques to regenerate hair follicles, potentially offering solutions for hair loss and promoting denser hair growth.

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

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

Plant-based proteins, like those derived from hemp and rapeseed can significantly contribute to a balanced diet and human daily nutritional requirements by providing essential nutrients such as protein, fiber, vitamins, minerals, and antioxidants. According to numerous recent research papers the consumption of plant-based proteins has been associated with numerous health benefits, including reduced risk of chronic diseases such as heart disease, diabetes, and certain cancers. Plant-based diets are often lower in saturated fat and cholesterol and higher in fiber and phytonutrients, which can support overall health and well-being. Present research investigates the nutritional attributes, functional properties, and potential food applications of hemp and rapeseed protein for a potential use in new food product development, with a certain focus on identifying anti-nutritional factors and bioactive compounds. Through comprehensive analysis, anti-nutritional factors and bioactive compounds were elucidated, shedding light on their impact on protein quality and digestibility. The study also delves into the functional properties of hemp and rapeseed protein, unveiling their versatility in various food applications. Insights from this research contribute to a deeper understanding of the nutritional value and functional potential of hemp and rapeseed protein, paving the way for their further utilization in innovative food products with enhanced nutritional value and notable health benefits.

Antibiotic resistant Pseudomonas aeruginosa infections are the primary cause of mortality in people with cystic fibrosis (CF). Yet it has only recently become appreciated that resistance mutations can also increase P. aeruginosa virulence, even in the absence of antibiotics. Moreover, the mechanisms by which resistance mutations increase virulence are poorly understood. In this study we tested the hypothesis that mutations affecting efflux pumps can directly increase P. aeruginosa virulence. Using genetics, physiological assays, and model infections, we show that efflux pump mutations can increase virulence. Mutations of the mexEF efflux pump system increased swarming, rhamnolipid production, and lethality in a mouse infection model, while mutations in mexR that increased expression of the mexAB-oprM efflux system increased virulence during an acute murine lung infection without affecting swarming or rhamnolipid gene expression. Finally, we show that an efflux pump inhibitor, which represents a proposed novel treatment approach for P. aeruginosa, increased rhamnolipid gene expression in a dose-dependent manner. This finding is important because rhamnolipids are key virulence factors involved in dissemination through epithelial barriers and cause neutrophil necrosis. Together, these data show how current and proposed future anti-Pseudomonal treatments may unintentionally make infections worse by increasing virulence. Therefore, treatments that target efflux should be pursued with caution.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

The aim of this study was to investigate the physicochemical characterization and biological activities of chitosan (CH) based composite films with the incorporation of chestnut flower essential oil (CFEO). The composite films were prepared by casting method and characterized in terms of structural, morphological and mechanical properties via FT-IR, XRD, UV, SEM and TGA. The results proved the significantly increased water vapor permeability (WVP), heat resistance, antibacterial and antioxidant capabilities of CH-CFEO films. The incorporation of CH and CFEO enhanced the UV blocking, which made the film shield almost all UV light. Films with the tensile strength of 6.37 ± 0.41 MPa and elongation at break of 22.57 ± 0.35% were got with 6 mg mL-1 CFEO. Subsequently, the fruit preservation experiments also confirmed that the composite films could effectively extend the shelf life of bananas through their excellent water vapor and oxygen barrier. These desirable performances enable our newly developed composite films to be a remarkable packaging material to solve the fresh fruit preservation dilemma.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

The emergence of antibiotic-resistant Campylobacter jejuni, a leading cause of gastroenteritis worldwide, presents a significant public health challenge requiring vigilant surveillance and disease control. This study aimed to characterize C. jejuni strains isolated in Romania from 2017-2020, focusing on genetic diversity, virulence, and antibiotic resistance determinants. The isolates underwent phenotypical testing, PCR, and antibiotic resistance assessment using Disc Diffusion Kirby–Bauer for ciprofloxacin, nalidixic acid, erythromycin, and tetracycline. Genetic analysis identified resistance and virulence genes, point mutations, and performed sequence typing (7-gene MLST) to determine genetic relatedness. Results indicated substitutions at position 86 in the amino acid sequence or position 257 in the nucleotide sequence of the gyrA gene in 47 fluoroquinolone-resistant isolates. Additionally, mutations in the rRNA23S gene at positions 2074 and 2075, associated with macrolide resistance, were found in 12 of the 66 isolates. Allelic profiles generated 38 sequence types (STs), including three new STs not present in the reference database. The sequence data analysis revealed a genetically diverse C. jejuni population with a weak clonal structure. This study provides crucial insights into the genetic diversity and antibiotic resistance of C. jejuni strains in Romania, highlighting the need for ongoing surveillance and control measures.

Intensive crop production and extensive use of harmful synthetic chemical pesticides create numerous socio-economic problems worldwide. Therefore, sustainable solutions are needed for insect pest control, such as biological control agents. The fungal insect pathogen Beauveria bassiana has shown considerable potential as a biological control agent against a broad range of insects. The insights into virulence mechanism of B. bassiana is essential to show the robustness of its use. B. bassiana has several determinants of virulence, including the production of cuticle-degrading enzymes (CDEs), such as proteases, chitinases, and lipases. CDEs are essential in the infection process as they hydrolyze the significant components of the insect's cuticle. Moreover, B. bassiana has evolved effective antioxidant mechanisms that include enzyme families that act as ROS scavengers, e.g., superoxide dismutases, catalases, peroxidases, and thioredoxins. In B. bassiana, the number of CDEs and antioxidant enzymes characterized in recent years. The enzymatic activities are crucial for the biological control potential and significantly advanced our understanding of the infection mechanism of B. bassiana. This review focuses on the progress detailed in the studies of these enzymes and provides an overview of enzymatic activities and their contributions to virulence.

Penicillium digitatum is the major postharvest pathogen of citrus fruit under Mediterranean climate conditions. In the present work, we have addressed the study of the role of P. digitatum’s proteases in virulence following two complementary approaches. In a first approach, we have undertaken the functional characterization of the P. digitatum prtT gene, which codes for a transcription factor previously shown to regulate extracellular proteases in other filamentous fungi. Deletion of prtT caused a significant loss in secreted protease activity during in vitro growth assays. However, there was no effect on virulence. Gene expression of the two major secreted acid proteases was barely affected in the ΔprtT deletant during infection of citrus fruit. Hence, no conclusion could be drawn on the role of these secreted acidic proteases on the virulence of P. digitatum. In a second approach, we have studied the effect of different protease inhibitors and chelators in virulence. Co-inoculation of citrus fruit with P. digitatum conidia and a cocktail of protease inhibitors resulted in almost a complete absence of disease development. Analysis of individual inhibitors revealed that the metalloprotease inhibitor 1,10-phenanthroline was responsible for the observed effect. The application of metal ions reverted the protective effect caused by the metallopeptidase inhibitor. These results may set the basis for the development of new alternative treatments to combat this important postharvest pathogen.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

By repeated unloading and loading of the excavation dynamic and static loads, repeated train dynamic and static loads of multi-factors, the underpass tunnel, cross tunnel engineering influence area rock layer, the existing tunnel structure of the three constitutes a multifaceted structure, multi-factor interaction system. Existing tunnels into the prediction theory model of the new tunnel excavation process of dynamic and static loads, dynamic and static loads of existing tunnels are mostly analyzed individually, the results of synergistic analysis needs to be improved. Based on the theory of the current layer method, the paper comprehensively considers the stiffness of the existing tunnel, the stiffness of the new tunnel, the excavation method load and the existing tunnel load, coupled with Peck's empirical formula, the theoretical model of deformation prediction for excavation of a two-lane highway tunnel under the tunnel through the existing railroad is proposed, and verified and optimized by numerical calculations and monitoring data, which proves the applicability and reliability of the theoretical model in the similar strata and the project promotion.

Chagas disease (CD) is a neglected tropical parasitic disease caused by the protozoan Trypanosoma cruzi. Unfortunately, the current etiological treatment for CD is unsatisfactory, due to the high toxicity and low cure efficacy of compounds, mainly during the chronic phase of this disease. Thus, the discovery of new drugs for the treatment of CD is urgent. In the present study, we report the synthesis of a series of guanidines and its evaluation in in vitro assays to determine the trypanocidal effects on the Tulahuen T. cruzi strain, transfected with a β-galactosidase reporter gene, in comparison to the cytotoxic effects on vertebrate cells. The most potent and selective compounds LQOF-G1 and LQOF-G29 were considered good drug prototypes and candidates for in vivo tests using mice. Both compounds possess an electron withdrawing group on the aniline moiety, namely a NO2 and Br group, respectively, which effectively decrease the electron density. LQOF-G29 stands out among the investigated compounds due to the replacement of the benzyl group by methyladamantane.

Monitoring of clients living with HIV encompasses a specific array of activities that routinely check on various aspects of ART following its initiation depending on the availability of resources in that particular state, among other factors as per guidelines from the World Health Organisation. This is a significant practice as it promotes positive health outcomes for patients and efficient utilisation of ART regimens to reduce resistance to the medication – hence it is a measure to guard avoidable costs. It also forms a basis on which decisions are made from. It can be done clinically by assessing for signs e.g., skin rash and symptoms e.g., nausea and vomiting, checking vital organ function and measuring weights across all populations, or can be also be done by assessing specimens for their respective viral loads, white blood cell count, pregnancy status or other infections such as hepatitis B. There have not been any special indications required for one to be eligible for monitoring during ART in developing countries; all qualify for routine monitoring even though some may be more frequent than others in cases of comorbidities such as renal failure where medications can be attributed to exacerbating the condition.

Leishmaniasis are neglected diseases that affect regions such as South Asia, South Africa and Latin America, less developed regions. Current treatment, for cutaneous, mucocutaneous and visceral leishmaniosis, which are the main forms of the disease, is based on the administration of pentavalent antimonial and amphotericin B. However, these drugs have low efficacy and high toxicity. For this reason, the search for new treatments for this disease is necessary, based on studies of new molecules and their conformations. The research proposed the conformational study of brominated guanidine compounds with potential antileishmanial activity using Nuclear Magnetic Resonance (NMR) and X-ray diffraction (XRD) techniques. The present study involves the bro-minated molecules, LQOF-G2, LQOF-G30, LQOF-G35 and LQOF-G35-Br. The later was synthesized by the reaction of LQOF-G35 with NBS under IR irradiation at 120 Watts of potency and dichloro-methane as solvent by 12-h of exposition. The obtained results demonstrated the efficiency of the bromination method, since two bromines atoms entered the molecule. Furthermore, NMR analysis showed the occurrence of a conformational change from Z to E when compound LQOF-G35 was brominated to LQOF-G35-Br. This feature was well confirmed by comparative DRX study of the LQOF-G35 and LQOF-G35-Br compounds. The antileishmanial activity of LQOF-G2 e LQOF-G35 motivated the synthesis of new brominated compounds LQOF-G30 e LQOF-G35-Br.

Graphene hybrid-filler polymer composites have emerged as prominent materials that revolutionize heavy industries. This study encapsulates the in-depth analysis of different influential factors such as filler/graphene type, aspect ratios, dispersion methods, filler-matrix compatibility, fiber orientation, synergistic effects, different processing techniques, and post-curing conditions that affect the processing, properties and determine the resultant applications of graphene hybrid polymer composites. Additionally, it discusses the substantial role of graphene collaboration with other fillers such as carbon nanotubes, silica, nano-clays and metal oxides to produce functionalized hybrid polymer composites with synergistically enhanced tailored properties to offer solutions for heavy industries like aerospace, automotive, electronics, and energy harvesting. The review concludes with some suggestions and outlook on the future of these composite materials by emphasizing the need for continued research to fully optimize their potential.

Porins are crucial proteins located in the outer membrane that directly influence antimicrobial resistance mechanisms and virulence in bacteria. In this study, a porin gene (Vp-porin) was cloned in V. parahaemolyticus, and the function of Vp-porin on biological characteristics and virulence was investigated. The results of sequence analysis showed that Vp-porin is highly conserved in Vibrio spp. and the predicted 3D structure showed it could form a transmembrane channel with 20 β barrel. Membrane permeabilization provides evidence that membrane integrity of ∆Vp-porin was damaged and the sensitivity to tetracycline, polymyxin B, rifampicin and cephalothin of ∆Vp-porin obvious increased. In addition, loss of Vp-porin damaged motility due to down-regulated flagellar synthesis. Besides, ∆Vp-porin exhibited attenuated cytotoxicity to Tetra-hymena. The relative survival rate of Tetrahymena infection with ∆Vp-porin was 86%, which is much high than that with WT (49%). Take together, Vp-porin in V. parahaemolyticus plays various roles in biological characteristics in membrane integrity, antimicrobial resistance and motility, and contributes to virulence.

Partial Differential Equations (PDEs) constitute a fundamental framework for modeling various physical phenomena across diverse fields such as physics, engineering, and finance. Solving PDEs accurately and efficiently remains a significant challenge, particularly when dealing with complex systems or high-dimensional data. In this paper, we present a novel approach based on deep learning techniques to investigate the effective factors in solving PDEs. Our methodology leverages the expressive power of deep neural networks to learn and represent the underlying relationships between input parameters and the solutions of PDEs. By incorporating domain knowledge into the network architecture and training process, our approach aims to provide insights into the key factors influencing the solution of PDEs. We demonstrate the effectiveness of our method through numerical experiments on various PDEs, showcasing its capability to identify important features and improve predictive accuracy. Our findings suggest that deep learning techniques offer a promising avenue for understanding and analyzing the complex dynamics inherent in PDEs, paving the way for enhanced computational methods in scientific and engineering applications.

Marine microalgae are a rich reservoir of natural compounds, including bioactives. Nonetheless, these organisms remain fairly unexplored despite their potential biotechnological applications. Culture collections with diverse taxonomic groups and lifestyles are a good source to unlock this potential and discover new molecules for multiple applications such as the treatment of human pathologies or the production of aquaculture species. In the present work extracts from 33 strains (including 20 dinoflagellates, 4 diatoms and 9 strains from other 7 algal classes), cultivated under identical conditions were examined for antiviral, antibacterial, anti-inflammatory and anti-cancer activities. Among these, antiviral and anti-inflammatory activities were detected in a few strains while antibacterial tests showed positive results in most assays. In turn, most trials did not show any anti-cancer activity. Wide differences were observed between species within the same class, in particular dinoflagellates which were better represented in this study. These preliminary findings pave the way for in-depth characterization of extracts with highest signals in each test, identification of compounds responsible of the biological activities found, and a further screening of the CCVIEO culture collection.

Ovarian cancer (OC) represents a significant challenge in the realm of gynecological cancers, characterized by poor survival rates and complex etiology. In this review, we delve into the se-lected genetic, environmental, and hormonal factors underpinning OC development. We have reviewed scientific databases searching for ovarian cancer genetic and epigenetic factors. We have included studies based on their relevancy. As a result of exploring ovarian carcinogen-esis, this systematic review contains data collected from 126 various works. The role of prominent genetic players such as BRCA mutations, DNA repair mechanisms, un-derscores the intricate landscape of OC susceptibility. We explore Li-Fraumeni and Lynch syn-drome, which impart a heightened predisposition to OC development. Hormonal factors such as estrogen, progesterone, and androgens are also discussed. Environmental alterations, ranging from lifestyle influences on OC to microbiome dysbiosis and lifestyle factors such as obesity, al-cohol consumption, and physical activity intersect with genetic and epigenetic pathways, shaping the risk landscape for OC. Through a meticulous examination of current literature, this review provides a nuanced under-standing of the multifactorial nature of OC, emphasizing the need for holistic approaches to prevention, diagnosis, and treatment.

Listeria ivanovii and L. monocytogenes, are the only pathogenic species of the genus Listeria and share many virulence factors and mechanisms of pathogenicity. L. ivanovii shows host tropism towards small ruminants and rodents and much lower virulence for humans compared to L. monocytogenes. However, severe infections caused by L. ivanovii, resulting in bacteremia, abortion and stillbirth, occasionally occurred in immunocompromised persons and in pregnant women, while in immunocompetent hosts L. ivanovii can cause gastroenteritis. In this review the updated knowledge on virulence aspects and distribution of L. ivanovii in the environment and in food are summarized. Recent research on its virulence characters at genome level gave indications on how pathogenicity evolved in this bacterial species. As for L. monocytogenes, L. ivanovii infections occur after the ingestion of contaminated food, so an overview of reports regarding its distribution in the food products was carried out to obtain indications on the categories of foods exposed to contamination by L. ivanovii. It was found that a wide variety of food products can be a source of this microorganism and that, like L. monocytogenes, L. ivanovii is able to persist in the food production environment. Studies on its ability to grow in enrichment and isolation media suggested that its occurrence in nature might be underestimated. Moreover, virulence varies among strains for differences in virulence character regulation, presence/absence of genetic regions and the possible instability of a Listeria pathogenicity genomic island, LIPI-2, which is unique to L. ivanovii. We can conclude that L. ivanovii, as a possible pathogen for animals and humans, requires more focused investigations regarding its occurrence in the environment and in food and on intra-species variability of pathogenic potential.

China's cotton production has shown a concentration to the advantageous regions in recent years. Based on the relevant data of cotton production in China, the study measures the cotton production agglomeration levels of 16 major cotton-producing provinces from 1978 to 2020, summarizes the spatiotemporal evolution characteristics of cotton production agglomeration, and analyzes the factors influencing cotton production agglomeration using spatial econometric models. The results indicate that: Firstly, since the opening-up and reform, China's cotton production agglomeration levels have shown an overall upward trend, exhibiting periodic dynamic changes over time, and the spatial pattern reveals a dynamic regional gradient. Secondly, there is spatial correlation among the production scales of cotton in different provinces, with a trend resembling a "U" shape, and the agglomeration form shows a low-level convergence. Thirdly, technological level, policies, substitute industrial products and foreign trade are identified as important factors. The cotton production in each province is spatially correlated through these factors, and there is also a presence of spillover effects. In conclusion, the government should prioritize considerations of various influencing factors to formulate tailored support policies, promote large-scale production to enhance technological levels, and focus on policies aimed at improving the quality of cotton.

Gastrointestinal bleeding (GIB) after heart transplantation (HT) remains a significant clinical issue. The study aimed to explore its incidence, trends, outcomes and clinical predictors of GIB in HT patients. Adult patients who underwent HT between 2015 and 2021 at Union Hospital were recruited and divided into two groups based on the presence or absence of postoperative GIB. Primary outcomes were evaluated by follow-up. Independent predictors of GIB after HT were identified by logistic regression analysis. A nomogram prediction model was constructed according to these independent variables, and the accuracy of the model was assessed using the receiver operating characteristic (ROC) curve and the calibration curve. Among 461 patients, 40 (8.7%) developed GIB post-HT. HT patients with postoperative GIB exhibited higher in-hospital, 30-day, 90-day and 1-year mortality (all P < 0.05). Multivariate analysis identified age, preoperative warfarin, postoperative continuous renal replacement therapy and postoperative nasogastric tube as independent risk factors for GIB following HT. The nomogram prediction model was performed using the 4 variables. The area under the curve (AUC) of this model was 0.852(95% CI: 0.787-0.917, P < 0.001) and the calibration curve was close to the ideal diagonal line. GIB following HT is associated with a poor clinical prognosis. The constructed nomogram, incorporating its independent risk factors, demonstrated a favorable predictive value for GIB.

Background and Objectives: The aim of this study was to determine the job-related and individual features that influence BS and depression levels among dentists working in faculties, oral and dental health centres (ODHC) and private clinics. Materials and Methods: This prospective, cross sectional study was carried out on dentists working in different regions of Turkey. Data were collected using an on-line questionnaire created using Google Forms. The questionnaire consisted of demographic data, Maslach BS Inventory (MBI) and Beck Depression Inventory (BDI) sections. Demographics were age, height, weight, marital status, blood type, gender, monthly income, income satisfaction and having enough free time. The dentists were divided into 3 groups as faculty, private clinic and ODHC according to the institutions in which they worked. Results: Of the total 290 dentists enrolled in the study, there were 172 males and 118 females with a mean age of 36.98±5.6 years. 128 of the dentists worked in faculties, 72 in private clinics and 90 in ODHCs. It was observed that women's EE scores were higher than men's (P&lt;0.05). No statistically significant difference was found between the groups when comparing BS and depression scores according to marital status and blood group (P&gt;0.05). There was no significant relationship between emotional exhaustion (EE), depersonalisation (DP), personal accomplishment (PA) and depression scores according to age, BMI and work experience, age, work experience and BMI (P&lt;0.05). It was found that the EE scores of the dentists working in the faculty and private clinic were lower than those of the dentists working in the ODHC (P&lt;0.05). Monthly income was associated with depression (r = -0.35). Conclusions: This study showed that dentists working in ODHCs had more EE. These findings suggest that there is a need for improvement in the working conditions of dentists, particularly in ODHCs.

The aim of the article is to verify differences in the perception of selected factors of sustainability among small and medium-sized enterprises (SMEs) in Central Europe. The subjects of analysis are factors such as corporate social responsibility (CSR), business risk sources (market, financial, personnel, and operational), reputation and social media, national support, social changes, and crisis events in business. The questionnaire was completed by 1,090 SMEs from the business environments of Visegrad Group countries. Statistical hypotheses were verified using Z-scores for two population properties. The most negatively perceived factors among owners and managers in the SME segment are national support and legislative changes. The most positively perceived factor is reputation and social media. The country of doing business is a significant factor. The perception of crisis events in business is most negative among Czech SMEs. More than 80% of Hungarian SMEs perceive their companies as sustainable. In comparison with Slovak and Polish SMEs, Hungarian perceptions are more positive in the context of sustainability. The country of doing business is the strongest factor in evaluating CSR indicators. The positive perception of CSR in Czech SMEs (43.9%) is lower than in other countries.

Measuring the impact of land use regulation on the land market involves identifying and classifying relevant impact factors related to the land market. The objective of this study was to identify land market impact factors in the context of the introduction of land use regulation in Nepal. A desktop review was carried out to identify preliminary set of impact factors, which were reclassified through intuitive analysis based on the degree of thematic closeness. Perspective-based impact factors were identified through the qualitative analysis of primary data collected through semi-structured interviews with the Nepalese land market stakeholders. These independently derived impact factors were compared with the desktop literature review impact factors resulting in fourteen land market impact factors across four dimensions, including transaction cost, valuation, mortgage availability, taxation, and compensation across the economic dimension; lot size, subdivision restrictions, and coordination across the institutional dimension; awareness, expectation and proximity across the social dimension; and risk reduction, quality of residential land, and suitability of zoning classification across the environmental dimension. There was significant overlap and commonality across factors identified from both the literature review and semi-structured interviews. The land market impact factors determined in the study may be adapted and generalized across other countries and could be utilized to better understand the impacts of land policy decisions on urban planning and development. Further research is recommended on the process to operationalize the use of these factors to quantify the impact of land use regulation on different land markets.

The FTF (Fusarium Transcription Factor) gene family is composed of two members (FTF1 and FTF2) with high sequence homology. Both genes encode Zn(II)2Cys6 binuclear zinc finger transcription factors involved in the modulation of virulence in the F. oxysporum species complex (FOSC). While FTF1 is a multicopy gene exclusive of highly virulent strains of FOSC and is located in the accessory genome, FTF2 is a single copy gene, located in the core genome, and well conserved in all filamentous ascomycete fungi, except yeast. The involvement of FTF1 in the colonization of the vascular system and regulation of the expression of SIX effectors has been stablished. To address the role of FTF2 we generated and characterized null FTF2 mutants in a F. oxysporum f. sp. phaseoli weakly virulent strain and analyzed them together with the equivalent mutants formerly obtained in a highly virulent strain. The results obtained highlight a role for FTF2 as a negative regulator of the production of macroconidia and demonstrate that it is required for full virulence and positive regulation of SIX effectors. In addition, gene expression analyses provide compelling evidence that FTF2 is involved in the regulation of hydrophobins likely required for plant colonization.

A probe of a patient, seeking help in an emergency ward of a French hospital in late December 2019 because of Influenza like symptoms, was retrospectively tested positive to COVID-19. Despite the early appearance of the virus in Europe, the prevalence and virulence appeared to be low for several weeks, before the spread and severity of symptoms increased exponentially, yet with marked spatial and temporal differences. Here, we compare the possible linkages between peaks of fine particulate matter (PM2.5) and the sudden, explosive increase of hospitalizations and mortality rates in the Swiss Canton of Ticino, and the Greater Paris and London regions. We also discuss the influence of Saharan dust intrusions on the COVID-19 outbreak observed in early 2020 on the Canary Islands. We find that high PM2.5 concentrations – possibly favored by air temperature inversions or Saharan dust intrusions – are not only modulating but even more so boosting severe outbreaks of COVID-19. We conclude that the overburdening of the health services and hospitals as well as the high over-mortality observed in various regions of Europe in spring 2020 can be linked to peaks of PM2.5 and likely particular weather situations that have favored the spread and enhanced the virulence of the virus. In the future, we recommend to monitor not only the prevalence of the virus, but also to consider the occurrence of weather situations that can lead to sudden, very explosive COVID-19 outbreaks.

Following the transfer of hospital services to provincial government oversight, it is essential to understand how such changes impact service quality and efficiency. This study aims to identify the factors affecting hospital service quality post-transfer and evaluate the role of professional nurses in maintaining service standards under new governance.We conducted the study at sub-district health-promoting hospitals using a mixed-methods design based on the Global Fund-HSS framework (2012), which categorizes factors into accessibility, processes, productivity, and outcomes. We collected data from 340 nurses and 400 patients using structured questionnaires. We divided the questionnaires into seven sections, which captured a range of metrics such as the personal data of nurses, hospital service activities, and leadership qualities. We employed a Likert scale to gauge perceptions and expectations of service quality. We used paired t-tests to compare performance metrics before and after the administrative transfer, one-way ANOVA to assess variability among different service units, and binary logistic regression to identify key determinants of service quality in our statistical analysis. The analysis revealed a significant correlation between the attitudes and competencies of healthcare teams and the levels of service quality. Notably, service units transferred less than 50% exhibited minimal changes, indicating that the degree of transfer significantly impacts service outcomes. Despite these variations, the fundamental mission of promoting health remained consistent. The study emphasizes the critical role of nurses and recommends further research to identify additional factors that could improve service quality in transferred healthcare facilities. This could contribute to improved healthcare delivery across restructured health systems.

For the first time in history, we have witnessed the origin and development of a pandemic. To handle the accelerated accumulation of viral mutations and to comprehend the virus' evolutionary adaptation in humans, an unparalleled program of genetic sequencing and monitoring of SARS-CoV-2 variants has been undertaken. Several scientists have theorized that, with the Omicron surge producing a more contagious but less severe disease, the end of COVID-19 is near. However, by analyzing the behavior shown by this virus for 2 years, we have noted that pandemic viruses do not always show a decreased virulence. Instead, it appears there is an evolutionary equilibrium between transmissibility and virulence. We have termed this concept “intermittent virulence”. The present work analyzes the temporal and epidemiological behavior of SARS-CoV-2 and suggests that there is a high possibility that new virulent variants will arise in the near future, although it is improbable that SARS-CoV-2´s virulence will be the same as was seen during the pandemic phase.

Abstract The COVID-19 pandemic is thought to began in Wuhan, China in December 2019. Mobility analysis identified East-Asia and Oceania countries to be highly-exposed to COVID-19 spread, consistent with the earliest spread occurring in these regions. However, here we show that while a strong positive correlation between case-numbers and exposure level could be seen early-on as expected, at later times the infection-level is found to be negatively correlated with exposure-level. Moreover, the infection level is positively correlated with the population size, which is puzzling since it has not reached the level necessary for population-size to affect infection-level through herd immunity. These issues are resolved if a low-virulence Corona-strain (LVS) began spreading earlier in China outside of Wuhan, and later globally, providing immunity from the later appearing high-virulence strain (HVS). Following its spread into Wuhan, cumulative mutations gave rise to the emergence of an HVS, known as SARS-CoV-2, starting the COVID-19 pandemic. We model the co-infection by an LVS and an HVS, and show that it can explain the evolution of the COVID-19 pandemic and the non-trivial dependence on the exposure level to China and the population-size in each country. We find that the LVS began its spread a few months before the onset of the HVS, and that its spread doubling-time is $\sim 1.59\pm 0.17$ times slower than the HVS. Although more slowly spreading, its earlier onset allowed the LVS to spread globally before the emergence of the HVS. In particular, in countries exposed earlier to the LVS and/or having smaller population-size, the LVS could achieve herd-immunity earlier, and quench the later-spread HVS at earlier stages. We find our two-parameter (the spread-rate and the initial onset time of the LVS) can accurately explain the current infection levels (R^2$\mathrm{=0.74}$; correlation p-value (p) of 5x10^-13$$). Furthermore, countries exposed early should have already achieved herd-immunity. We predict that in those countries cumulative infection levels could rise by no more than 2-3 times the current level through local-outbreaks, even in the absence of any containment measures. We suggest several tests and predictions to further verify the double-strain co-infection model and discuss the implications of identifying the LVS.

Cellulose nanocrystals (CNCs) are cellulose-derived nanomaterials that can be easily obtained, e.g., from vegetable wastes produced by circular economies. They show promising antimicrobial activity and the absence of side effects and toxicity. This study investigated the ability of CNCs to reduce microbial adherence and biofilm formation using in vitro microbiological models reproducing the oral environment. Microbial adherence by microbial strains of oral interest, Streptococcus mutans and Candida albicans was evaluated on the surfaces of salivary pellicle-coated enamel disks in the presence of different aqueous solutions of CNCs. The antibiofilm activity of the same CNC solutions was tested against S. mutans and an oral microcosm model based on mixed plaque inoculum using a continuous-flow bioreactor. Results showed an excellent anti-adherent activity of the CNCs against the tested strains from the lowest concentration tested (0.032 wt.%). Such activity was significantly higher against S. mutans than C. albicans, suggesting a selective anti-adherent activity against pathogenic strains. At the same time, there was a minimal albeit significant antibiofilm activity (at least 0.5 and 4 wt.% CNC solution for S. mutans and oral microcosm, respectively). This makes CNCs particularly interesting as anticaries agents, encouraging their use in the oral field.

Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.

Background: Colorectal cancer (CRC) patients experienced multiple chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine the chemotoxicity's prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (Ps 65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (Ps

Introduction: Cleft lip with or without cleft palate (CL/P) is the most common congenital face anomaly in the world of multifactorial etiology. Objective: To determine the prevalence and characteristics of cleft palate. To identify associated risk factors to guide prevention and/or prenatal detection for early intervention and better health outcomes. To assess the rehabilitation protocols after operations in cleft palate. Design: Retrospective descriptive and clinical study. Patients: One hundred and three children with cleft palate treated in the Department of Head and Neck Surgery Clinic for Children and Young Adults, Department of Clinical Pediatrics, University of Warmia and Mazury, were included in the study. Methods: Records evaluation was conducted regarding sex, cleft type, mother occupation, parents education, histories of cleft in any of parents. The data were analyzed using R (R core team 2021) and the ordinal logistic regression analyses. Results: Children of stressed mothers during pregnancy had 9.4 times higher odds of having bilateral cleft. While there was no evidence that children sex, order of birth, and body mass as well as risk of maternal toxicity at work or reporting infections or drugs toxicity had a significant effect on the dependent variable. Conclusions: Children of parents with cleft history and having low educated mothers had higher probability of bilateral cleft palate. Children of stressed mothers during pregnancy had higher odds of having bilateral cleft. In literature, there is a lack of reports about rehabilitation in different operations methods in children with cleft palates.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

In the context of sustainable development, integrating the work aspect into health promotion systems is essential, ensuring that employees maintain a healthy balance between their professional and personal lives, which respects and amplifies the potential of every individual. Lately, there has been a noticeable shift of medical professionals from the public to the private sector. This trend paints a bleak picture, highlighting the vulnerabilities of a system teetering on the brink of failure, with significant impacts on patient care. Among the myriad reasons behind this shift, burnout stands out prominently. Medical professionals face increasing pressures due to understaffing, limited organizational support, and insufficient resources, leading to feelings of cynicism, exhaustion, and detachment from their roles. Utilizing the Maslach et al. questionnaire, we assessed the risk of burnout among physicians in public hospitals to identify and underscore preventive measures and improvements, correlating our findings with key aspects of organizational empowerment. Our research indicates that enhancing interpersonal relationships and resources—both within teams and between the organization and its physicians—is crucial for the revival of the healthcare system. This approach aims at improving the delivery of healthcare services and offering appropriate recognition to healthcare professionals, aligning with the principles of sustainable employment.

Following the transfer of hospital services to provincial government oversight, it is essential to understand how such changes impact service quality and efficiency. This study, conducted from 1 March 2023 to 31 March 2024 at sub-district health-promoting hospitals in Thailand, aims to identify the factors affecting hospital service quality post-transfer and evaluate the role of profes-sional nurses in maintaining service standards under new governance. Utilizing a mixed-methods design based on the Global Fund-HSS framework (2012), which categorizes factors into accessibility, processes, productivity, and outcomes, we collected data from 340 nurses and 400 patients through structured questionnaires. These questionnaires were divided into seven sec-tions, capturing metrics such as the personal data of nurses, hospital service activities, and lead-ership qualities. We employed a Likert scale to gauge perceptions and expectations of service quality and conducted paired t-tests to compare performance metrics before and after the admin-istrative transfer. One-way ANOVA was used to assess variability among different service units, and binary logistic regression helped identify key determinants of service quality. The analysis revealed a significant correlation between the attitudes and competencies of healthcare teams and the levels of service quality. Notably, service units transferred less than 50% exhibited mini-mal changes, indicating that the degree of transfer significantly impacts service outcomes. Despite these variations, the fundamental mission of promoting health remained consistent. The study emphasizes the critical role of nurses and recommends further research to identify additional factors that could improve service quality in transferred healthcare facilities, potentially contributing to enhanced healthcare delivery across restructured health systems.

Aiming at the APF algorithm in the collision-free path planning and LQR algorithm tracking process, there are problems such as unreachable target points, local optimization, low safety coefficient of autonomous lane change collision avoidance tracking control and poor stability, this paper proposes an optimized APF method, which solves the defects of the traditional artificial potential field method by adding the distance adjustment factor, the safety distance protection model and the sub-target virtual potential field, and at the same time generates the autonomous driving car collision-free path. The path tracking control system is designed based on feed-forward control and DLQR controller, in which the vehicle dynamics state space model is used as the basis, the model is linearized and discretized, and the corresponding constraint variables are set to minimize the control command objective cost function under the constraints, and the objective of the DLQR controller.The objective is to accurately determine the steering angle in order to achieve path tracking and eliminate the lateral error between the reference path and the actual path caused by external interference.Finally, the simulink model and CarSim parameter configuration joint simulation platform are built, and different obstacle scenarios and different speeds are selected for collision-free path planning and tracking motion simulation research and analysis, which verifies the accuracy and practicability of the algorithm, and shows more obvious advantages in obstacle avoidance ability, path smoothing degree, and collision avoidance safety stability. The ideas proposed in this paper are expected to be further extended and popularized to actual path planning problems, which has important practical significance and engineering value.

Purpose: This integrated review aims to identify and analyze the multifactorial contributors to the longevity of direct restorations, focusing on tooth-, patient-, and dentist-related factors. Materials and Methods: A literature search was performed using an electronic database, PubMed/Medline, Web of Science, and Scopus, between 1980 and 2024. Titles and abstracts of papers that evaluated aspects categorized into tooth-related, patient-related, and dentist-related factors influencing restoration failure were selected and screened. Full-text assessments were conducted, and the extracted data were compiled, summarized, and synthesized. The reference lists of the collected papers were also screened, and relevant citations were included in this review. Data were gathered from clinical and laboratorial studies, systematic reviews, and meta-analyses to provide a comprehensive understanding of restoration longevity. Results: Among the tooth-related factors, multiple-surface restorations, deep margins, tooth location, and tooth vitality significantly impact restoration survival. Patient-related factors such as medical conditions, risk predictors of caries, age, sex, parafunctional habits, smoking, periodontal health, number of restorations, and socioeconomic status all play crucial roles. Regarding dentist-related factors, the decision-making process, age, experience, and dentist manual dexterity are vital aspects. Furthermore, the technique used, including isolation methods for moisture control, as well as the type of dental practice (large group vs. small practice), notably influenced the restoration survival. Conclusions: The longevity of dental restorations is influenced by a complex interplay of tooth-related, patient-related, and dentist-related factors. Strategies to improve restoration outcomes should consider all these multifactorial contributors. Continuing professional education, diligent patient guidance on the factors that influence restoration survival, careful material selection and restorative technique, and tailored individual treatment are crucial factors to reduce failure rates and improve the lifespan of restorations.

Background and Objectives: Age-related macular degeneration (AMD) is one of the major causes of central vision loss in the older age group and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As the inflammation and involvement of the immune system are strongly suggested to have a central role to promote the degenerative process and to stimulate the onset of complications, we aimed to analyze the prevalence of serum anti-retinal (ARA) and anti-endothelial cell antibodies (AECA) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably area of geographic atrophy (GA). Materials and Methods: We enrolled 41 patients with dry AMD and 50 sex- and age-matched healthy controls without AMD. The presence of ARA was determined by indirect immunofluorescence using monkey retina as an antigen substrate, while the presence of AECA was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARA were detected 36 (87.8%) AMD patients (titers range from 1:20 to 1:320) and in 16 (39.0%) (titers range from 1:10 to 1:40) of controls (p=0.0000). Twenty of the 41 patients (48.8%) were positive for AECA, while in a control group AECA were present only in 5 sera (10.0%). The titers of AECA in AMD patients ranged from 1:100 to 1:1000 and in the control group the AECA titers were 1:100 (p=0.0001). There were no significant correlations between the presence of AECA and disease activity. Conclusions: This study provides evidence for the possible involvement of an autoimmune process against retina and retinal vessel antigens in the pathogenesis of geographic atrophy associated with dry AMD.

Polycystic ovary syndrome (PCOS) is a common condition in reproductive-age women. Women with PCOS are at higher risk of pregnancy complications including gestational diabetes (GDM). The prevalence of PCOS and GDM varies according to the diagnostic criteria used. The mechanism for the occurrence of GDM in women with PCOS is still unclear. Materials &amp; Methods- A systematic search of the electronic database was done using keywords like PCOS, and GDM to include studies between April 2008 and March 2023 where uniform diagnostic criteria were used. Studies were excluded with high-risk of bias after the assessment of bias, and meta-analysis was done with relative risks and confidence intervals. Results &amp; Discussion-Out of 1896 search results, 95 were selected for full-text. The quality of the studies was scrutinized and a total of 28 studies were included as they fulfilled the inclusion criteria. The incidence of GDM in women with PCOS was found to be 10.55 % (2.9- 54.9%) from pooled data involving 1,280,245. The prevalence of PCOS in women diagnosed with GDM was found from pooled data of 36,351 women in retrospective studies to be 2.47% (1.5- 50.1%). Selection predominantly included cohort studies, most commonly from China. The meta-analysis reported the risk of GDM is higher in women with PCOS than in those without PCOS (HR: 1.59, 95% CI: 1.27–1.91, p &lt; 0.001). Family history of diabetes, ethnicity, pre-pregnancy BMI, insulin resistance, gestational weight gain, use of assisted reproductive techniques, and multifetal gestation were the risk factors for GDM in women with PCOS. Conclusion- The prevalence of GDM in patients with PCOS is high, but the causality is complex. The newer predictive models are promising in clarifying the causative relationships, yet use various parameters at different cut-offs. There is a need for the development of universally acceptable parameters for the early prediction of GDM in women with PCOS.

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.