Diversity as well as temporal and spatial changes of the proportional abundances of different antibiotics (cycling, mixing or combinations thereof) have been hypothesised to be an effective administrative control strategy in hospitals to reduce the prevalence of antibiotic-resistant pathogens in nosocomial or community-acquired infections. However, a rigorous assessment of the efficacy of these control strategies is lacking. The main purpose here is to present a mathematical framework for the assessment of control stategies from a processual stance. To this end, we adopt diverse measures of heterogeneity and diversity of proportional abundances based on the concept of entropy from other fields and adapt them to the needs in assessing the impact of variations in antibiotic consumption on antibiotic resistance. Thereby, we derive a family of diversity measures whose members exhibit different degrees of complexity. Most important, we extent these measures such that they account for the assessment of temporal changes in heterogeneity including otherwise undetected diversity-invariant permutations of antibiotics consumption and prevalence of resistant pathogens. We apply a correlation analysis for the assessment of associations between changes of heterogeneities on the antibiotics and on the pathogen side. As a showcase, which serves as a proof-of-principle, we apply the derived methods to records of antibiotic consumption and prevalence of antibiotic-resistant germs from University Hospital Dresden. Besides the quantification of heterogeneities of antibiotics consumption and antibiotic resistance, we show that a reduction of prevalence of antibiotic-resistant germs correlates with a temporal change of similarity with respect to the first observation of antibiotics consumption, although heterogeneity remains approximately constant. Although an interventional study is pending, our mathematical framework turns out to be a viable concept for the assessment and optimisation of control strategies intended to reduce antibiotic resistance.

A new disease causing the tan to light brown blighted stems and pods has occurred in 2.6% pea (Pisum sativum L.) plants with an average disease severity rating of 3.7 in Chapainawabganj district, Bangladesh. A fungus with white appressed mycelia and large sclerotia was consistently isolated from symptomatic tissues. The fungus formed funnel-shaped apothecia with sac-like ascus and endogenously formed ascospores. Healthy pea plants inoculated with the fungus produced typical white mold symptoms. The internal transcribed spacer sequences of the fungus were 100% similar to that recovered from an epitype of Sclerotinia sclerotiorum, considering the fungus to be the causative agent of white mold. Mycelial growth and sclerotial development of S. sclerotiorum were favored at 20°C and pH 5.0. Glucose was the best carbon sources to support hyphal growth and sclerotia formation. Bavistin and Amistar Top inhibited the radial growth of the fungus completely at the lowest concentration. In planta, foliar application of Amistar Top showed the considerable potential to control the disease at 1.0% concentration until 7 days after spraying, while Bavistin prevented infection significantly until 15 days after spraying. A large majority (70.93%) of genotypes including tested released pea cultivars were susceptible, while six genotypes (6.98%) appeared resistant to the disease. These results could be important for management strategies aiming to control the incidence of S. Sclerotinia and eliminate yield loss in pea.

Sustainable agricultural production is endangered by several ecological factors such as drought, extreme temperatures, excessive salts, parasitic ailments, and insect pest infestation. These challenging environmental factors may have adverse effects on future agriculture production in many countries. In modern agriculture, conventional crop breeding techniques alone are inadequate for achieving the increasing population’s food demand on a sustainable basis. The advancement of molecular genetics and related technologies are promising tools for the selection of new crop species. Gene pyramiding through marker assisted selection (MAS) and other techniques have accelerated the development of durable resistant/tolerant lines with high accuracy in the shortest possible period of time for agricultural sustainability. Gene stacking has not been fully utilized for biotic stress resistance development and quality improvement in most of the major cultivated crops. This review emphasizes on gene pyramiding techniques that are being successfully deployed in modern agriculture for improving crop tolerance to abiotic and biotic stresses for sustainable crop improvement.

Introduction: Bacterial resistance is a worldwide public health problem, requiring new therapeutic options. An alternative approach to this problem is the use of animal toxins, such as phospholipases (PLA₂) isolated from snake venom, which have important biological activities. Bothrops erythromelas is one of the snake species in the Northeast of Brazil that attracts great medical-scientific interest. Here we aimed to purify and characterize a PLA₂ from B. erythromelas, searching for heterologous activities against bacterial biofilm. Methods: Venom extraction and quantification were followed by RP-HPLC in C18 column, MALDI-ToF mass spectrometry and sequencing by Edman degradation. All experiments were monitored by specific activity using 4-nitro-3 (octanoyloxy) benzoic acid (4N₃OBA) substrate. In addition, hemolytic tests and anti-bacterial tests including action against Escherichia coli, Staphylococcus aureus and Acinetobacter baumannii, were carried out. Moreover, tests of antibiofilm action against A. baumannii were also performed. Results: PLA₂, after one purification step, presented 31 N-terminal amino acid residues, and molecular weight of 13656.4 Da with enzymatic activity confirmed in 0.06 µM concentration. Antibacterial activity against S. aureus (IC₅₀ = 30.2 µM) and antibiofilm activity against A. baumannii (IC₅₀ = 1.1 µM) were observed. Conclusions: This is the first time that PLA₂ purified from B. erythromelas venom has appeared as an alternative candidate in studies of new antibacterial medicines.

The molecular interaction between the nematode and the host plant cells is complex and sophisticated. Initial contact with the plant parasitic nematodes (PPNs) triggers immune response in the host plant system which includes the release of toxic molecules. To put a bridle on this immune response, PPNs trigger pivotal cytoprotective mechanisms, such as antioxidant and detoxification pathways. Mechanisms of these pathways have been studied in PPNs and the specific genes involved have been targeted for gene silencing research in view of developing novel control measures. However, one of the important group of proteins involved in detoxification pathways known as ABC-transporters are not being studied until recently in PPNs. This opinion article focusses on the current knowledge and future prospects of ABC transporters in PPNs.

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analysed its oral pharmacokinetics and its effects on a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), b) insulin signaling in the liver and c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associate with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation while sustaining glycaemia through liver-based mechanisms of glycolysis control.

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

Pseudomonas aeruginosa (P. aeruginosa) produces a suite of virulence factors that are coordinated by Quorum Sensing (QS) contributing to its disease-causing ability in aquaculture. The present study is first of its kind to obtain information regarding the presence and distribution of five QS genes, three virulence genes viz: lasI, lasR, rhlI, rhlR, rhlAB, toxA, aprA and plcH and seven of the Extended-spectrum βlactamases (blaVEB, blaPER, blaTEM,, blaSHV, blaCTX-M1, blaCTX-M2 and blaCTX-M3) of Pseudomonas species isolated from fish meat by direct PCR. Bacterial identification was based mainly on conventional biochemical techniques using the Vitek 2, automated system. Phenotypic sensitivity of antibiotics was established by the agar disc diffusion technique through 16 various antimicrobial drugs. Quantification of their in vitro production of numerous virulence genes outside the cell that are QS dependent namely, pyocyanin, elastase, alkaline protease, biofilm and cytotoxicity of Vero cell was as well executed. Fifteen genes demonstrated an enormous variety in their association. The total number of Pseudomonas species isolates were 30/100 to be identified by the API 20NE system as P. aeruginosa 12/30 (40%), P. fluorescens 8/30 (27%), P. putida 6/30 (20%) and P. alkylphenolia 4/30 (13%). The outcomes of this study have great significance for the strategic designation of QS quenching.

The deaf impairment is among the most substantial health problem worldwide, that can lead to various personal, economical, and social crisis. Therefore, it is critical for developing an efficient way to facilitate communication between deaf-dumb impaired and normal people. Herein, we have rationally designed a new digitally computerized and mobile smart system as an efficient communication tool between deaf impaired and normal Arabian people. This is based on two main steps, including creating a digital output for the hand gestures using gloves flex sensors equipped with a three-axis accelerometer that is controlled using a microcontroller. The digital results are compared to that in a words-based “database”, where Arabs use expressions not alphabet in their communication. The second step is translation or conversion the outputs of the first stage into written texts and voices. The newly developed system allows Arabian deaf to translate words of ordinary people into gestures using a speech recognition system with an impressive accuracy over 90 % without the needing for a webcam, colored gloves, and/or online translator. The presented system can be used on any android or windows.

Gray cast iron is one of the most important engineering materials that has many applications in various industries including automotive and machinery manufacturing due to its mechanical properties, wear resistance, machining potentials and low price. In this research effect of adding aluminum and silicon to composition of gray cast iron on microstructure and wear resistance was studied. Moreover, it was investigated the role of formation of Fe-Al-Si intermetallic compound in final properties of the alloy. For studying wear resistance of samples pin-on-disc method was carried out. The results showed that addition of aluminum to gray cast iron causes formation of ferrite matrix, which leads to a decrease in hardness value. Increasing silicon content up to 2 wt. % in cast iron with 4 wt. % aluminum intensifies the formation of ferrite matrix, while further increase to 3 wt. % causes emerging a Fe-Al-Si intermetallic phase. Improvement in hardness value was achieved by increasing silicon content from 3 wt. % to 4 wt. % due to the increased percentage of intermetallic phase. Effect of intermetallic phase on decreasing wear rate was showed by studying microstructure and hardness values, however the lowest wear resistance was observed in aluminum bearing cast iron containing 2 wt. % silicon.

Antimicrobial resistance (AMR) is one of the greatest public health challenges we are currently facing. To develop effective interventions against this, it is essential to understand the processes behind the spread of AMR. These are partly dependent on the dynamics of horizontal transfer of resistance genes between bacteria, which can occur by conjugation (direct contact), transformation (uptake from the environment) or transduction (mediated by bacteriophages). Mathematical modelling is a powerful tool to investigate the dynamics of AMR, however its application to study the horizontal transfer of AMR genes is currently unclear. In this systematic review, we searched for mathematical modelling studies which focused on horizontal transfer of AMR genes. We compared their aims and methods using a list of predetermined criteria, and utilized our results to assess the current state of this research field. Of the 43 studies we identified, most focused on the transfer of single genes by conjugation in Escherichia coli in culture, and its impact on the bacterial evolutionary dynamics. Our findings highlight the existence of an important research gap on the dynamics of transformation and transduction, and the overall public health implications of horizontal transfer of AMR genes. To further develop this field and improve our ability to control AMR, it is essential that we clarify the structural complexity required to study the dynamics of horizontal gene transfer, which will require cooperation between microbiologists and modellers.

Gray cast iron is one of the most important engineering materials that has many applications in various industries including automotive and machinery manufacturing due to its mechanical properties, wear resistance, machining potentials and low price. In this research effect of adding aluminum and silicon to composition of gray cast iron on microstructure and wear resistance was studied. Moreover, it was investigated the role of formation of Fe-Al-Si intermetallic compound in final properties of the alloy. For studying wear resistance of samples pin-on-disc method was carried out. The results showed that addition of aluminum to gray cast iron causes formation of ferrite matrix, which leads to a decrease in hardness value. Increasing silicon content up to 2 wt. % in cast iron with 4 wt. % aluminum intensifies the formation of ferrite matrix, while further increase to 3 wt. % causes emerging a Fe-Al-Si intermetallic phase. Improvement in hardness value was achieved by increasing silicon content from 3 wt. % to 4 wt. % due to the increased percentage of intermetallic phase. Effect of intermetallic phase on decreasing wear rate was showed by studying microstructure and hardness values, however the lowest wear resistance was observed in aluminum bearing cast iron containing 2 wt. % silicon.

Antimicrobial stewardship efforts are an emphasis among many institutions around the world to combat inappropriate antimicrobial utilization, rising healthcare costs and emerging antimicrobial resistance. Implementation of new innovative strategies may be challenging for many institutions with limited or constrained resources. Using proven effective methods as evidenced by other institutions in the peer-reviewed literature may offer an opportunity to evaluate institution-specific practices, which may be implemented locally. A structured examination and survey of the peer-reviewed, stewardship literature by an expert group of clinicians, scholars and educators determined the most influential publications from 2016. Herein, the top thirteen manuscripts are reviewed to aid clinicians identify potential stewardship opportunities and serve as an educational tool for trainees and others.

Drug resistance has become an extremely serious problem worldwide. Antibiotic resistance genes (ARGs) entering the environment with wastewaters promote replenishment of the resistome of natural microbioms. Distribution of several clinically significant ARGs in wastewaters of Rostov-on-Don (Southern Russia), lower reaches of the Don River and natural waters of the neighboring region was investigated. Metagenomic DNA samples isolated from 250 ml of wastewaters or natural waters and 200 mg of surface sediments were used for the study. Identification of the ARGs was carried out with end-point detection PCR. Presence of NDM, OXA-48, CTX-M, VanA, VanB, ErmB, and TetM/TetO genes was detected in urban wastewaters. Samples of wastewater treatment plant (WWTP) sewage were enriched with ARGs in contrast to non-treated wastewaters from the sewage collector. NDM, VanA, ErmB, TetM/TetO genes were found only in wastewaters and were absent in samples of natural waters and surface sediments. Only OXA-48, VanB and CTXM genes were found in natural waters and surface sediments. The described ARGs are quite typical for urban and hospital wastewaters. The target ARGs were detected in the samples connected to the anthropogenous sources of pollution such as Rostov municipal WWTP or livestock enterprise effluents.

Candida glabrata has thoroughly adapted to successfully colonize human mucosal membranes and survive in vivo pressures prior to and during antifungal treatment. Out of all the medically relevant Candida species, C. glabrata has emerged as a leading cause of azole, echinocandin, and multidrug (MDR: azole + echinocandin) adaptive resistance. Neither mechanism of resistance is intrinsic to C. glabrata, since stable genetic resistance depends on mutation of drug target genes, FKS1 and FKS2 (echinocandin resistance), and a transcription factor, PDR1, which controls expression of major drug transporters, such as CDR1 (azole resistance). However, another hallmark of C. glabrata is the ability to withstand drug pressure both in vitro and in vivo prior to stable ‘genetic escape’. Additionally, these resistance events can arise within individual patients, which underscores the importance of understanding how this fungus is adapting to its environment and to drug exposure in vivo. Here, we explore the evolution of echinocandin resistance as a multistep model that includes general cell stress, drug adaptation (tolerance), and genetic escape. The extensive genetic diversity reported in C. glabrata will be highlighted.

Background: Staphylococcus aureus (S. aureus) occasionally threatens the life of the host as a persistent pathogen even though it is normal flora of humans and animals. We characterized drug resistance in S. aureus isolated from animal carcasses and milk samples from the abattoirs and dairy farms in the Eastern Cape Province. Methods: A 1000 meat swab samples and 200 raw milk samples were collected from selected abattoirs and dairy farms in the Eastern Cape Province, South Africa. S. aureus was isolated and positively identified using biochemical tests and confirmed by molecular methods. Antibiotic susceptibility test against 14 different antibiotics was performed against all isolates. Antibiotic resistance genes were also detected. Results: Of the 1200 samples collected, 134 (11.2%) samples were positive for S. aureus. Resistance ranged from 71.6% for penicillin G to 39.2% for tetracycline. Resistance gene (blaZ) was detected in 13 (14.9%), while msrA was found in 31 (52.5%) of S. aureus isolates. Conclusions: The present result shows the potential dissemination of multidrug-resistant S. aureus strains in the dairy farms and abattoirs in the Eastern Cape. Therefore, this implies that the organism may rapidly spread through food and pose serious public health risk

In 2016 northern Nigeria experienced a devastating infestation by the tomato leaf miner, leading to soaring in prices of tomato across the country. Unfortunately, information on the bionomics and resistance status of this pest is lacking in northern Nigeria, hampering appropriate control measures. Here, we identified to species level, and using conventional and synergist bioassays characterised pesticides resistance profile of a field population of a tomato leaf miner from northern Nigeria. Highest resistance was obtained with λ-cyhalothrin (Type II pyrethroid) with a low mortality (18.52% at 56hr) and LD₅₀ of 7461.474ppm. Resistance was also established toward propoxur and chlorpyrifos-methyl with average mortalities each of 56% and LD_50s of 1023.51ppm and 106.351ppm, respectively. Highest susceptibility was seen with abamectin with mortality of 86% and LD₅₀ of 0.034ppm. Pre-exposure to piperonyl butoxide significantly recovered λ–cyhalothrin susceptibility (mortality = 90% and LD₅₀ = 0.92ppm) implicating the P450 monoxygenases in the resistance. No significant changes in mortalities were obtained on pre-exposure to diethyl maleate and triphenyl-phosphate- inhibitors of glutathione S-transferases and carboxylesterases, respectively. The finding of resistance to these agricultural pesticides will sensitize stakeholders across Nigeria to take action to manage the resistance at an early stage before it gets out of hand.

Saturated fatty acids are implicated in the development of metabolic diseases, including obesity and type 2 diabetes. There is evidence, however, that polyunsaturated fatty acids can counteract the pathogenic effects of saturated fatty acids. To gain insight into the early molecular mechanisms by which fatty acids influence hypothalamic inflammation and insulin resistance, we performed time-course experiments in a hypothalamic cell line, using different durations of treatment with the saturated fatty acid palmitate, and the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). Western blot analysis revealed that palmitate elevated the protein levels of phospho(p)AKT in a time-dependent manner. This effect seems involved in the pathogenicity of palmitate, as temporary inhibition of the PI3K/AKT pathway by selective PI3K inhibitors prevented palmitate-induced insulin resistance. Similarly to palmitate, DHA also increased levels of pAKT, but to a weaker extent. Co-administration of DHA with palmitate decreased pAKT close to the basal level after 8 h, and prevented palmitate-induced insulin resistance after 12 h. Measurement of the inflammatory markers pJNK and pNFκB-p65 revealed tonic elevation of both markers in the presence of palmitate alone. DHA alone transiently induced elevation of pJNK, returning to basal levels by 12 h treatment. Co-administration of DHA with palmitate prevented palmitate-induced inflammation after 12 h, but not at earlier time points.

Gut microbiota play critical roles in development of obese-related metabolic diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes, and insulin resistance, which highlighted the potential of gut microbiota-targeted therapies on these diseases. There are various ways that can manipulate gut microbiota including probiotics, prebiotics, synbiotics, antibiotics and some active components from herbal medicines. In this review, we first reviewed the main roles of gut microbiota in mediating the development of NAFLD, and the advances in gut microbiota-targeted therapies on NAFLD in both the experimental and clinical studies, as well as the conclusions on the prospect of gut microbiota-targeted therapies in the future.

Rifampicin is one of the most important chemotherapeutic agents used in the treatment of tuberculosis. M. tuberculosis clinical strains resistant to rifampicin harbor mainly mutation in an 81-base pair region of rpoB. These mutations mainly consist of single amino acid substitutions. However insertions also can be related with rifampicin resistance strains. Herein, we described an insertion of 12 nucleotides in clinical isolates of M. tuberculosis resistant to rifampicin, all obtained from inmates. To evaluate the importance this insertion in surviving and drug resistance, it were carried out fitness experimental assays as well as in silico studies of 3D structural models, molecular docking simulations and virtual screening. The medical records of the seven patients showed all were previously treated to tuberculosis. Growth curves shown that the insertion determines a biological cost when compared to wild type rpoB and katG; or the double mutated rpoB S531L and katG S315T. From docking and molecular dynamics simulations it can be inferred that the insertion does not affect the process of synthesis of RNA transcripts. On the other hand, in the mutant RNAP-RIF complex rifampicin confirmed a low affinity interaction for the mutant form. Interesting, virtual screening for potential inhibitors for wtRNAP and mRNAP using a library of 1446 compounds approved by the FDA showed that the best ligands were mainly compounds with antibiotic activity, although the targets involved in the pharmacological action are other than RNAP. In conclusion, seven strains of M. tuberculosis RIF resistant that present an insertion of four amino acids in RNA polymerase showed by growth curve assays, a biological cost. Further, bioinformatics tools had characterized the putative drug resistance dynamic as well as the maintenance of RNA polymerase activity.

The aim of this study was to investigate the effect of β-Hydroxy-β-methylbutyrate (HMB) supplementation on anti-inflammatory cytokines including IL-4, IL-10 and TGF-β during an acute bout of resistance exercise (RE) in young resistance trained men. Ten resistance-trained men in a randomized, double-blind, placebo-controlled and crossover study, were administered a 7-day HMB supplementation (3×1 g.d-1 of HMB) and placebo (3×1 g.d-1 of Maltodextrin) with a 7 days washout period. After supplementation periods, subjects performed three sets of bench press, lat pull down, leg extension, leg curl, biceps curl, triceps curl and shoulder press to failure with 85% of one repetition to maximum (1RM). Blood samples were obtained before- (Pre), immediately post- (IP) and 1 hour-post RE (1h P) to assess serum concentrations of IL-4, IL-10 and TGF-β1. The data were analyzed using 2 (treatment: HMB and PL) × 3 (time points: Pre, IP and 1hP) repeated measures analysis of variance (ANOVA) followed by the Bonferroni post hoc test with a significant level of p<0.05. Serum IL-4 was significantly higher at IP resistance exercise in HMB compared to placebo. Circulating IL-4 and TGF-β1 were significantly raised at IP compared to Pre in both HMB and placebo treatments. No significant differences between treatments were observed for IL-10 and TGF-β1at any time points. In conclusion, HMB supplementation increased the circulating level of IL-4 during RE in resistance-trained men, which may attenuate inflammation and facilitate adaptation to RE.

The aim of this paper is to develop a composite coating on St 304 steel employing TIG process. Ti wire cored with graphite powder is used as the means of coating material. The process parameters are varied in order to develop coating with optimum characteristics (i.e., hardness and wear resistance). The microstructure of the coating is analyzed with SEM and XRD. It is found that both of the hardness and wear resistance increase as the current increases while both of these properties decrease as the travelling speed increases. It is found that the coated samples with composite layers have more hardness than the substrate and it could range up to 1100 HV being almost 4.5 times higher than the hardness of St 304. Likewise, the wear resistance of coating is observed to be 4.5 times higher than that of substrate. The high performance of coating, as revealed by microstructural analysis, is due to formation of TiC and Cr₂₃C₆ .The optimum conditions to produce the coating are proposed to be 120 A current and 3.17 mm/s travel speed.

Modelling water vapour flow, heat transfer and porosity in porous adsorbent is somewhat challenging simulation problem. Primary macroscopic water vapour flow models, such as Darcy's law, fail to predict the pressure drop entirely correctly for the reason that many of flow parameters not considered because of the simplifications that remain made for the multi-scale structure of the porous adsorbents. For one to develop a good physical understanding of such water vapour flows and the accuracy of existing 3D simulation models, there is a need for some accurate 3D geometry to be studied. This present work describes two-phase water vapour flow and adsorption/ desorption performed on porous adsorbent by a Dynamic vapour sorption (DVS). The CFD simulation results are associated with experiments results. It is decided that for such complex porous adsorbent CFD simulation problems the use of COMSOL Multiphysics and SolidWorks flow simulation will be utilised.

Cytochrome P450 monooxygenases (P450s) and UDP-glycosyltransferases (UGTs) are involved in the evolution of insecticide resistance. Leptinotarsa decemlineata (Say), Colorado potato beetle (CPB), is the notorious insect that has developed resistance to various of insecticides including neonicotinoids. This study investigated whether the differentially expressed P450 genes CYP9Z140 and CYP9AY1 and UGT gene UGT321AP1, found from our transcriptome results conferred resistance to thiamethoxam in L. decemlineata. Resistance monitoring showed that sampled field populations of L. decemlineata adults collected from Urumqi City, Qapqal, Jimsar and Mulei County of Xinjiang in 2021-2023 developed low levels to thiamethoxam with resistance ratios ranging from 6.66- to 9.52-fold. Expression analyses indicated that CYP9Z140, CYP9AY1, and UGT321AP1 were significantly upregulated in thiamethoxam-resistant populations compared with susceptible population. The expression of all three genes also increased significantly after thiamethoxam treatment compared with control. Spatiotemporal expression patterns showed that the highest expression of CYP9Z140 and CYP9AY1 occurred in pupae and midgut, whereas UGT321AP1 was highly expressed in adults and Malpighian tubules. Knocking down all three genes individually or simultaneously using RNA interference increased the sensitivity of adult L. decemlineata to thiamethoxam. These results suggest that overexpression of CYP9Z140, CYP9AY1, and UGT321AP1 contribute to the development of thiamethoxam resistance in L. decemlineata and provide scientific basis for improving new resistance management of CPB.

Identification of drug targets and biochemical investigations on mechanisms of action is a are major issues in modern drug development. The present article reviews the classical “one drug” – “one target” paradigm. Novel methods for target deconvolution and for investigation of resistant strains based on protein mass spectrometry have shown that multiple gene products and adapta-tion mechanisms are involved in responses of pathogens to xenobiotics. This review is focused on protozoan pathogens. The conclusions can, however, be extended to chemotherapies against other pathogens or cancer. For this review we have searched Pubmed (pubmed.ncbi.nlm.nih.gov) and Web of Science (webofscience.com) using the key words listed below (status May 2024)

There are clear signs that the COVID-19 pandemic has had a straining impact on the higher education sector in South Africa and the far reaches of the world. This chapter examines (Science, Technology, Engineering, Mathematics) STEM lecturers’ experiences with digital assessments and perspectives on the continuity of digital transformation in the higher education sector in the post-COVID-19 era at one of South Africa’s rural universities. In 2022, a survey of ten (10) lecturers was conducted and the reports were also consulted by four (4) e-learning practitioners to obtain their views on the use of online learning and contact courses in the post-pandemic period. A qualitative research approach was used to understand the puzzling issues faced by STEM lecturers at a previously disadvantaged institution in Limpopo Province. The results of this study show that there is a puzzling conundrum that hinders the integration of effective online learning. Furthermore, online education as the new normal in the post-COVID-19 era seems unattainable due to extremely complex and difficult-to-understand mathematical symbols. Software and tools proved to be limitations in terms of establishing an interactive learning environment for students and lecturers on online learning platforms. Lecturers’ use of learning and teaching platforms deteriorated due to numerous unknown challenges, but also the tightening of COVID-19 restrictions. Furthermore, the results showed that science and mathematics lecturers believe that contact learning remains irreplaceable across generations and eras as some are not technology enthusiasts. This paper recommends that the lack of technological systems as well as technological resistance and reluctance to adopt transformative pedagogy and innovative practices, should not be viewed as a thorny issue to end the dominance of online education in STEM courses. Keywords: connectivism, Learning Management Systems, affordances, technological resistance, Moodle, transformative pedagogy

Multiple myeloma (MM) is a common type of cancer that unfortunately leads to a significant number of deaths each year. The majority of the reported MM cases are detected in the advanced stages, posing significant challenges for treatment. Additionally, all MM patients eventually develop resistance or experience relapse, therefore advances in treatment are needed. However, developing new anti-cancer drugs, especially for MM, requires significant financial investment and a lengthy development process. The study of drug repurposing involves exploring the potential of existing drugs for new therapeutic uses. This can significantly reduce both time and costs, which is typically a major concern for MM patients. The utilization of pre-existing non-cancer drugs for various myeloma treatments presents a highly efficient and cost-effective strategy, considering their prior preclinical and clinical development. The drugs have shown promising potential in targeting key pathways associated with MM progression and resistance. Thalidomide exemplifies the success that can be achieved through this strategy. This review delves into the current trends, the challenges faced by conventional therapies for MM, and the importance of repurposing drugs for MM. This review highlights a noncomprehensive list of conventional therapies that have potentially significant anti-myeloma properties and anti-neoplastic effects. Additionally, we offer valuable insights into the resources that can help streamline and accelerate drug repurposing efforts in the field of MM.

Staphylococcus aureus bacteremia continues to be associated with significant morbidity and mortality, despite improvements in diagnostics and management. Persistent infections pose a major challenge to clinicians and have been consistently shown to increase the risk of mortality and other infectious complications. S. aureus, while typically not considered an intracellular pathogen, has been proven to utilize an intracellular niche, through several phenotypes including small colony variants, as a means for survival that has been linked to chronic, persistent, and recurrent infections. This intracellular persistence allows for protection from the host immune system and leads to reduced antibiotic efficacy through a variety of mechanisms. These include antimicrobial resistance, tolerance, and/or persistence in S. aureus that contribute to persistent bacteremia. This review will discuss the challenges associated with treating these complicated infections and the various methods that S. aureus uses to persist within the intracellular space.

Resistance against amitraz in varroa mite populations has become a subject of interest in recent years due to increasing reports of reduced field efficacy of amitraz treatments, especially from some beekeepers in France and the United States. The loss of amitraz as a reliable tool to effectively reduce varroa mite infestation in the field could severely worsen the position of beekeepers in the fight to keep varroa infestation rates in their colonies at low levels. In this publication, we present data from French apiaries, collected in the years 2020 and 2021. These data include field efficacy of an authorized amitraz-based varroa treatment (Apivar®) and results of laboratory sensitivity assays of varroa mites exposed towards the reference LC90 concentration of amitraz. In addition, a total of 240 varroa mites from Eastern, Central, and Southern regions in France that were previously classified as either “sensitive” or “resistant” towards amitraz in a laboratory sensitivity assay were genotyped. The genetic analyses of mite samples are focused on the β−adrenergic-like octopamine receptor, which is considered as the main target site for amitraz in varroa mites. Special attention was given to a single nucleotide polymorphism (SNP) at position 260 of the ORβ-2R-L gene that had previously been described by Hernández Rodríguez et al. (2021) as associated to the resistance to amitraz in French varroa mites. Our findings confirm that amitraz resistance occurs in patches or “islands of resistance” with a less severe reduction in treatment efficacy compared to pyrethroid resistance or coumaphos resistance in varroa mites. The results of our genetic analyses of varroa mites call into question the hypothesis of the SNP at position 260 of the ORβ-2R-L gene being directly responsible for amitraz resistance development.

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

The domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 hr, 48 hr and 5 days post infection condition. Total 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides corresponding to 129 proteins were identified. Functional annotation of proteome data analysis reveals activation of RIG-I-like receptor and Jak-STAT signaling pathways, that lead to induction of interferon stimulated genes (ISGs) expression. The pathway analysis of phosphoproteome datasets also confirms the activation of RIG I, Jak-STAT signaling, NF-kappa B signaling and MAPK signaling pathways in the lung tissues. The induction of ISGs proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5 and PKR) establishes protective antiviral immune response in duck lung tissue. Further, the protein-protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1 and MAPK1 as main hub proteins that might play important roles in disease progression in ducks. Together, functional annotation of proteome and phosphoproteome datasets reveals the molecular basis of the disease progression and disease resistance mechanism in ducks infected with HPAI H5N1 virus.

Acetamiprid is a broad-spectrum neonicotinoid insecticide used in agriculture to control aphids. While recent studies have documented resistance to acetamiprid in several aphid species, the underlying mechanisms are still not fully understood. In this study, we analyzed the transcriptome and metatranscriptome of a laboratory strain of the pea aphid, Acyrthosiphon pisum (Harris, 1776), with reduced susceptibility to acetamiprid after nine generations of exposure to identify candidate genes and the microbiome involved in the adaptation process. Sequencing of the transcriptome of both selected (RS) and non-selected (SS) strains allowed the identification of 14858 genes and 4938 new transcripts. Most of the differentially expressed genes were associated with catalytic activities and metabolic pathways involving carbon and fatty acids. Specifically, the alcohol-forming fatty acyl-CoA reductase (FAR) and acyl-CoA synthetase (ACSF2), both involved in the synthesis of epidermal wax layer components, were significantly upregulated in RS, suggesting that adaptation to acetamiprid involves the synthesis of a thicker protective layer. Metatranscriptomic analysis revealed subtle shifts in the microbiome of RS. These results contribute to a deeper understanding of acetamiprid adaptation by the pea aphid and provide new insights for aphid control strategies.

Abstract: Exercise has been repeatedly shown to be safe and beneficial for cancer survivors. However, there is no normative guideline for exercise prescription, and it is under exploration. Therefore, this literature review aims to provide some advice for the formulation of exercise prescriptions for patients with breast cancer-related lymphedema (BCRL) from the perspective of reducing lymphedema severity. A review of relevant studies published before November 2023 was conducted using three scientific databases PubMed, Embase, and Scopus. A total of 2696 articles were found. Eventually, 13 studies fulfilled the inclusion criteria and were included in this literature review. We concluded daily, or nearly daily exercise at home can be recommended. Moreover, reduced lymphedema severity may not be maintained after ceasing the exercise program, so exercise should be a lifelong practice.

This study investigates the effects of Zinc (4wt.%) and severe plastic deformation on the mechanical properties of AZ61 magnesium alloy through the stir-casting process. The severe plastic deformation (equal channel angular pressing (ECAP)) has been done followed by T4 heat treatment. The microstructural examinations revealed that the addition of 4wt.%Zn enhances the uniform distribution of β-phase, contributing to a more uniformly corroded surface in corrosive environments. Additionally, dynamic recrystallization (DRX) significantly reduces the grain size of as-cast alloys after undergoing ECAP. The attained mechanical properties demonstrate that after a single ECAP pass, AZ61 + 4wt.%Zn alloy exhibits optimal yield strength (YS), ultimate compression strength (UCS), and hardness. This research highlights the promising potential of AZ61 + 4wt.%Zn alloy for enhanced mechanical and corrosion-resistant properties, offering valuable insights for applications in diverse engineering fields.

Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug resistant (MDR) K. pneumoniae are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) K. pneumoniae (n=676) isolated from patients hospitalized in 13 intensive care units (ICUs) in 6 European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility. Majority were colistin-susceptible (CS) (n=597, MIC 2 µg/ml). 288 CS isolates were randomly selected for population analysis profiling (PAP) to assess CHR prevalence. CHR was detected in 108/288 CS K. pneumoniae. No significant association was found between the occurrence of CHR and country, MIC-value, K-antigen type and O-antigen type. Overall, 92% (618/671) of the K. pneumoniae were MDR with high prevalence among CS (540/592) and CR (98.7%, 78/79) isolates. In contrast, proportion of carbapenemase-producing K. pneumoniae (CP-Kpn) was higher among CR (72.2%, 57/79) than CS isolates (29.1%, 173/594). Proportions of MDR and CP-Kpn were similar among CHR (MDR: 85%, 91/107; CP-Kpn: 29.9%, 32/107) and CS isolates (MDR: 91%, 539/592; CP-Kpn: 29.1%, 153/59). WGS analysis of PAP isolates showed diverse insertion elements in mgrB or even among technical replicates underscoring the stochasticity of the CHR phenotype. CHR isolates showed high ST diversity (Simpson’s diversity index, SDI: 0.97, in 52 of the 85 STs tested). CR (SDI: 0.85) isolates were highly associated with specific STs (ST101, ST147, ST258/ST512, P ≤ 0.003). The widespread nature of CHR among MDR K. pneumoniae in our study urge the development of rapid HR detection methods to inform on the need for combination regimens.

This research concerns the virtual reconstruction and technical constructive analysis of the emblematic and disappeared Matriz church of Ambato city, whose structure was demolished after the collapse of its vaults in the 1949 earthquake, about which it was said to have had deficiencies in its construction. Through an exhaustive historical review of documents and images, its constructive hypothesis was achieved, and using photogrammetry technique, its virtual reconstruction was obtained, where, through the interpretation and understanding of the generated plans, the verification of its technical and constructive characteristics associated with its hypothetical mechanical behavior inherent to its stone construction was carried out. For the structural study, the principle of the Limit Analysis of Structures was used, where through a graphic static approach, the technical stability conditions of a masonry structure are established, in this case, to give an interpretation to the possible poor execution of the church's work, and eventual cause that could have contributed to the collapse of its vaults.

Zn2+ has been implicated in the regulation of intestinal redox and microbial homeostasis, and we recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in mammalian cells. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in stress resistance of intestine. Expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using GEO database. Systemic TRPC3-knockout (KO) and TRPC6-KO mice were treated with dextran sulphate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6-KO mice, but not TRPC3-KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in TRPC6-KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.

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

Background: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV PrEP have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6-months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population. Methods: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals. Results: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals. Conclusions: We conclude that in high antimicrobial consumption populations, the association between antimicrobial consumption and resistance may be attenuated.

Diarrhea-related mortality remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diar-rheal infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of alkaloid-related compounds) was evaluated in vitro against selected diarrheagenic bacteria (Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Shigella flexneri, Vibrio parahaemolyticus, and Yersinia enterocolitica). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combinations of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against S. flexneri at a FICI value of 0.086. Combinations of the agents tested in this study can thus be used for the development of new anti-diarrheal medications. However, studies focusing on their in vivo anti-diarrheal activity and safety are required before any consideration for utilization in human medicine.

Although global life expectancy has increased over the past 20 years due to improvements in managing infectious diseases, one in five people still succumbs to infections. Humanity is tirelessly working towards developing vaccines and antimicrobial agents in response to this ongoing threat. However, pathogens continue to acquire numerous resistance mechanisms and proliferate. Meanwhile, the COVID-19 pandemic has prompted us to recognize that focusing solely on the killing strategies of immunology and microbiology in complex and multisystemic infectious diseases is insufficient for understanding survival. In essence, there is a need for a treatment approach centered on disease tolerance, capable of alleviating pathology and/or promoting physiological functions in conjunction with the existing strategies of host immune response and pathogen destruction. Against this backdrop, this narrative review comprehends and introduces microbiome therapeutics, which recently garnered attention as next-generation treatments regarding two defense strategies against infectious diseases. First, we delineate the application of existing probiotics and then the microbiome in infectious diseases. Subsequently, we expand this concept to encompass host microbiome crosstalk and present related microbiome therapeutics' current status and direction. Ultimately, the review presents a fresh perspective on understanding microbiome therapeutics in infectious diseases based on a cooperative defense system.

Bacterial wilt (BW), caused by Ralstonia solanacearum, is one of the devastating diseases of tomatoes (Solanum lycopersicum L.). The use of resistant cultivars and breeding for genetic resistance is the most effective, economical, and environmentally friendly management strategy for this disease. It is necessary to screen diverse germplasm and cultivated genotypes to identify resistant resources and to develop resistant cultivars in tomatoes to combat the changing pathogen isolates. This study evaluated 40 United States Department of Agriculture (USDA) tomato accessions for their BW resistance to R. solanacearum isolate P822 under greenhouse conditions. The tomato plants were inoculated and visually assessed to observe symptoms and disease severity was scored on a scale of 0 to 4 (0 = no leaf wilted, 1 = 25% of leaves wilted, 2 = 50% leaves wilted, 3 = 75% of leaves wilted, 4 = 100% leaves wilted). Five accessions PI 645370, PI 647306, PI 600993, PI 355110, and PI 270210 were observed as BW resistance with PI 645370 showing the greatest resistance. The broad-sense heritability was estimated as 59.9% based on a 0-4 scale of disease incidence and 42.8% based on the disease severity index for BW resistance. Two distinct clusters (sub-populations) were detected among 39 of the 40 accessions, consisting of 3 and 2 BW resistant accessions in each cluster, respectively, suggesting differences in the genetic base in the five resistance accessions. The resistant accessions will contribute significantly to the tomato breeding program to develop new cultivars with BW resistance.

To achieve a micro-destructive and rapid measurement of the wood density of standing trees, this study investigated the feasibility of using the micro-drilling resistance method, formulated a mathematical model, explored the potential for a unified model across multiple tree species, and analyzed the influence of moisture content on measurement accuracy. First, 231 tree cores and drill resistance data were sampled from Pinus massoniana, Cunninghamia lanceolate, and Cryptomeria fortunei. The basic density and moisture content of each core were measured, and the average value of each resistance data record was calculated. Second, the average drill resistance, the natural logarithm of average drill resistance, and absolute moisture content were used as independent variables, while the wood basic density was used as the dependent variable. Third, the total model of the three tree species and sub-model for each tree species were established through a stepwise regression method. Finally, the accuracy of each model was compared and analyzed with that of using the average basic density of each tree species as an estimated density. The results revealed that the estimation accuracy of the sub-model for each tree species was 1.670 percentage points higher than the average value of each tree species used as the density estimation value for these tree species. Additionally, except for Cryptomeria fortunei, the natural logarithm of drill resistance significantly influenced the wood density model at a significance level of 0.05. Moreover, moisture content significantly affected the total model and sub-models of Pinus massoniana at a significance level of 0.05. The estimation accuracy of the total mathematical model was 2.125 percentage points lower than that achieved using the average basic density of each tree species to predict their density. The results indicated the feasibility of using the micro-drilling resistance method to measure the wood density of standing trees. Moreover, the relationship between wood density and drill resistance did not follow a linear pattern, and moisture content slightly influenced the drill needle resistance. Furthermore, the establishment of a mathematical model for each tree species was deemed essential. This study provides valuable guidance for measuring the wood density of standing trees through the micro-drilling resistance method.

The ESKAPE pathogens are public health concerns worldwide, defining the present major antibiotic resistance issues: E. faecium vancomycin-R, S. aureus methicillin-R, Ps. Aeruginosa and A. baumannii carbapenem-R, resistance to 3rd generation cephalosporins of Kl. pneumoniae and Enterobacter spp. Covid-19 pandemic disturbed the health care usual procedures, contributing to the spread of antibiotic-resistant bacteria. The present study retrospectively assessed the prevalence and antimicrobial resistance (AMR) profile of ESKAPE microorganisms during 2020-2022 in a multidisciplinary emergency hospital from Romania, based on microbiological reports. The AMR issues mainly interest the urology department. ESKAPE group accounts for 33.5% of the total bacterial isolated. The specific AMR of ESKAPE pathogens cumulates 30.9%, while antimicrobial multidrug resistance characterizes 21% from all ESKAPE strains. Kl. Pneumoniae, followed by S. aureus, and Ps. aeruginosa are the main hospital problems concerning the ESKAPE surveillance. The directions of the near future antibiotic stewardship program focus to revise the clinical protocols for diagnostic and treatment in each department, to intensify the bacteriological samples collection, to improve the microbiological diagnostic techniques for AMR identification, to continue the epidemiological current actions of surveillance, control, and education.

Mechanical damage of plant tissues leads to the activation of methanol production and its release in the atmosphere. The gaseous methanol or vapors emitted by the damaged plant induce resistance in neighboring intact plants to bacterial pathogens but create favorable conditions for the viral infection spread. Among Nicotiana benthamiana methanol-inducible genes (MIGs) most are associated with plant defense and intercellular transport. Here we characterize NbMIG21 that encodes a 209-aa protein (NbMIG21p) which does not share any homology with annotated proteins. NbMIG21p was demonstrated to contain nucleolus localization signals (NoLS). Co-localization studies with fibrillarin and coilin, nucleolus and Cajal bodies marker proteins, revealed that NbMIG21p is distributed between these subnuclear structures. Our results show that recombinant NbMIG21 possess DNA-binding properties . Similar to gaseous methanol effect an increased NbMIG21 expression leads to the downregulation of the nuclear import of NLS-containing proteins as was demonstrated on the model GFP-NLS protein. Moreover, upregulated NbMIG21 facilitates tobacco mosaic virus (TMV) intercellular transport. We identified NbMIG21 promoter (PrMIG21) and showed that it is methanol-sensitive thus induction of NbMIG21 expression occurs at the level of transcription. Our findings suggest that methanol-activated NbMIG21 might participate in creating favorable conditions for the viral reproduction and spread.

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

Goji berries, long valued in Chinese medicine and cuisine for their wide range of medicinal benefits, are considered a 'superfruit' and functional food. Out of the nearly 100 Lycium species known for their genetic diversity, L. barbarum and L. chinense currently dominate the market. Due to increasing market demand and concerns about food safety and sustainability, Europe and the Americas are expanding the local goji berry production, using as starting material plants originated from China. European breeding programs are focusing on Lycium to develop varieties adapted to local conditions, especially in response to climate change. By 2023, Romania registered seven goji berry varieties, both from L. barbarum and L. chinense species, without incorporating local germplasm. Advanced genomic studies, including NGS sequencing of five cultivated and three wild goji berry plant genomes, have been conducted to analyse their genetic variation, with a particular focus on the BODYGUARD 3 and 4 genes. This research uncovered significant differences between cultivated and wild genotypes, both in the entire genome and specifically in the BODYGUARD genes, providing crucial insights for goji berry breeders to support the development of goji berry cultivation in Romania.

Magnesium alloy stents have been extensively studied in the field of biodegradable metal stents due to their exceptional biocompatibility, biodegradability and excellent biomechanical properties. Nevertheless, the specific in vivo service environment causes magnesium alloy stents to degrade rapidly and fail to provide sufficient support for certain time. This paper presents an overview of the development history and protection strategies for magnesium alloy stents. Alloying, optimizing stent structure and preparing protective coating have improved the corrosion resistance of magnesium alloy stents. Based on the corrosion mechanism of magnesium alloy stents, as well as their deformation during use and environmental characteristics, we present some novel solution strategies aiming at reducing the corrosion rate of magnesium alloys and enhancing the comprehensive performance of magnesium alloy stents. These strategies include adapting protective coatings for the deformation of the stents, preparing rapid endothelialization coatings to enhance the service environment of the stent, and constructing coatings with self-healing functions. It is hoped that this review can help to understand the development of magnesium alloy cardiovascular stents and solve the problems related to magnesium alloy stents in clinical applications at the early implantation stage.

In the present study, bivalent nanovaccines of S. iniae and F. covae were administered by immersion vaccination at 30 and 40 days after hatching (DAH), and the third vaccination was orally administered by feeding at 50 DAH. Five different groups were designed: group 1 was set as the control group, and groups 2-4 were vaccinated using the same protocols. ELISA revealed that the levels of total IgM and specific IgM to S. iniae, and F. covae were significantly elevated in groups 2-4 at 10, 20, and 30 days after vaccination (DAV). A qRT‒PCR analysis of immune-related genes revealed significantly higher IgT expression in the vaccinated groups compared with the control group, as revealed by 44-100-fold changes in the vaccinated groups compared with the control (p &lt; 0.001) at every tested time point after vaccination. All vaccinated groups expressed IgM, MHCIIα and TCRα at significantly higher levels than the control group at 10 and/or 20 DAV (p &lt; 0.05). In the S. iniae challenge tests, the survival of vaccinated groups 2-4 ranged from 62.15 ± 2.11 to 75.70 ± 3.36%, which significantly differed from that of the control group (44.44 ± 1.92%). Similarly, all vaccinated groups showed higher survival rates of 68.89 ± 3.85 to 77.78 ± 5.09% during F. covae challenge than the control groups (50.00 ± 3.33%) (p &lt; 0.05).

Monoclonal antibody (mAb) therapy has revolutionized the treatment of various diseases, including cancer and autoimmune disorders. However, the emergence of SARS-CoV-2 variants, as well as other pathogenic variants, poses challenges in maintaining the therapeutic efficacy of mAbs. In this mini review article, we aim to explore the strategies to overcome variants resistance in mAb therapy against viral infections. Firstly, we discuss the mechanisms through which variants can evade the neutralizing effects of mAbs. Understanding these mechanisms is crucial in developing targeted approaches to combat resistance. Next, we delve into the strategies being pursued to address variants resistance. These include developing new mAbs or antibody cocktails that target multiple epitopes, engineering mAbs with improved binding affinities or enhanced neutralizing capabilities, and exploring alternative therapeutic modalities such as bispecific antibodies or antibody-drug conjugates. Furthermore, we highlight the role of computational modeling and artificial intelligence in predicting variant escape mutations and aiding in the design of more effective mAbs. Additionally, we examine the importance of continuous surveillance and monitoring of emerging variants to inform treatment strategies. This article emphasizes the urgent need for proactive approaches to tackle variants resistance in mAb therapy. By combining innovative design strategies, computational modeling, and vigilant surveillance, we can maintain the therapeutic effectiveness of mAbs and stay ahead in the battle against evolving pathogens and viral infections.

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

Staphylococcus aureus are commensal bacteria present on skin and mucosae in both humans and animals, but they can also be found in food, water and in various environments. They are also considered a major pathogen having a great morbidity leading to a wide range of infections. They are included in the list of most virulent and antimicrobic resistant bacterial pathogens (ESKAPE, Escherichia coli, Staphylococcus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecalis and faecium)) by the Center for Disease Control and Prevention (CDC), and S. aureus is part of the worldwide threat represented by the presence of antimicrobial resistance (AMR). The outcomes of an epidemiological investigation on 26,430 S. aureus isolates from a global public database (NPDIB; NCBI Pathogen Detection Isolate Browser) support the evidence of significant differences in the distribution of isolates and ARGs (Antimicrobial Resistance Genes) clusters among geographical areas of origin and among sources of the isolates. Moreover, the ARGs cluster patterns suggest an association between the isolates from human and animal populations. This outcome and the large diffusion of the pathogens among human and animal populations support the importance of gaining information on the epidemiology of these infections with a One Health approach.

Objectives: Accumulating evidence suggests that physical activity (PA) is an efficient intervention to maintain functional capabilities and mitigate physiological changes in the older population. However, an attempt has yet to be made to comprehensively investigate the published landscape on the subject. Methods: This study had two aims. The first aim was to perform a bibliometric analysis for two keywords, “aging” and “PA”, to analyze the research trend. Since ‘frailty’ is the most noticeable co-occurring keyword with the two keywords, the second aim was to investigate the effects of PA, particularly resistance training (RT), on frailty via meta-analysis to provide a summary of the current evidence base. Results: Bibliometric analysis revealed that the number of publications on this research topic has gradually increased, highlighting the importance of understanding the role of PA in aging. A meta-analysis found that RT had significant beneficial effects on physical frailty factors, including handgrip strength, lower limb strength, balance, gait speed, and stair climbing ability. Conclusion: These findings demonstrate that RT is an effective intervention for improving physical function in frail populations; thus it has important implications for the development of PA programs for older adults with frailty. Future research is warranted to explore the optimal dose, frequency, and duration of RT programs for older adults, as well as the potential benefits of combining RT with other forms of PA, such as aerobic or balance exercises.

Obesity, characterized by the excessive accumulation of body fat, contributes to a multitude of physiological dysfunctions. This paper explores the complex relationship between obesity and various risk factors and complications, shedding light on critical health implications. Obesity triggers alterations in insulin, leptin, adiponectin, cytokines, and insulin-like growth factors, fostering conditions conducive to cancer initiation. Aberrations in nutrient-dependent intracellular signaling pathways, driven by the excess nutrition characteristic of obesity, contribute to the neoplastic transformation of cells. The Body Mass Index (BMI) correlates directly with adiposity, underlining its significance in cancer risk. Furthermore, insulin and insulin-like growth factors, notably IGF-2, play pivotal roles in this relationship. The expression of IR-A receptors is elevated in cancer. Obesity and cardiovascular diseases share a strong association. Obesity elevates the risk of fatal events like myocardial infarction. High cholesterol levels contribute to atherosclerosis in the aorta and coronary arteries. The severity of coronary artery disease is influenced by plaque formation characterized by calcium deposits. Obesity is also linked to hypertension and increased ventricular mass, exacerbating cardiovascular risks. Hypercholesterolemia and hypertension correlate with a high Body Mass Index (BMI). Obesity is intricately connected to insulin resistance, particularly evident in childhood obesity. It entails a gradual decline in insulin sensitivity, leading to elevated insulin levels in the bloodstream. Insulin resistance is a central factor in the development of Type 2 Diabetes Mellitus. Obesity also results in elevated triglyceride levels and reduced high-density lipoproteins, contributing to atherogenic dyslipidemia and a heightened risk of atherosclerosis. Additionally, obesity is associated with various other disorders, including epilepsy, depression, and neuropsychological problems. Beyond its physiological impact, obesity is associated with significant psychosocial challenges. Studies indicate that individuals with obesity face a higher risk of depressive symptoms, often related to overeating and unhealthy dietary patterns. The social withdrawal tendencies of obese individuals exacerbate these symptoms, with higher rates of depression observed in this group. OSA, a sleep disorder characterized by intermittent breathing cessation during sleep, is strongly correlated with obesity. Approximately 58% of obese individuals experience OSA, with higher Body Mass Index (BMI) associated with an increased risk. Weight reduction has been found to mitigate the severity of OSA and related arrhythmias. Continuous positive airway pressure (CPAP) therapy demonstrates effectiveness in reducing visceral fat accumulation and leptin levels. This comprehensive review underscores the intricate web of health implications associated with obesity, emphasizing the critical need for preventive measures and intervention strategies to address the multifaceted challenges posed by this global health concern.

In Benin, Xanthomonas oryzae pv. oryzae (Xoo) causing bacterial blight (BLB) was first described in 2013 on wild rice Oryza longistaminata. No studies have been conducted on Beninese Xoo strains and resistant rice varieties. The aim of this study is to check whether Xoo has already spread to cultivated varieties and to screen some rice accessions for the main resistance genes detection. To achieve this aim, rice leaves showing typical BLB symptoms were collected from various rice fields in Benin and analyzed by PCR to identify Xoo-specific sequences. In addition, seventy-five rice accessions were examined to identify Xoo resistance genes. The results showed that Xanthomonas oryzae (Xo) had been identified in Banikouara and Malanville. In addition, Sphingomonas sp was detected in several rice fields. A Xo-Sphingomonas Sp co-infection was also noted. 47 of 75 rice accessions examined (62.66%) carried Xoo resistance genes with 3 (4%) and 40 (53.33%) of xa5 and Xa21 respectively. None of the accessions had neither Xa7 nor Xa13 resistance genes. Three accessions had both xa5 and Xa21 genes. In addition, the rice isogenic lines IRBB60 and IRBB21used as positive controls, were found to be susceptible. These results indicate that Xo has evolved from a wild rice to cultivated varieties in northern Benin. Consequently, a varietal improvement program must be implemented with varieties having resistance genes to prevent a BLB pandemic in Benin.

Tungsten carbide inserts (TCI) and polycrystalline diamond compact (PCD) cutters used in two types of drill bits for drilling oil and gas wells were evaluated by a pin-on-disc test. The morphology of the worn surface was characterized by scanning electron microscopy (SEM). The behavior of corrosion resistance was evaluated with the electrodynamic polarization technique. The polycrystalline diamond compact cutter has a higher hardness, better corrosion, and wear behavior compared to tungsten carbide.

Resistance training is beneficial to adults for improving muscle strength and reducing the body composition. Nevertheless, little is known regarding online resistance training on anthropometric parameters and muscular strength (MS) in overweight female adolescents. This study aimed to examine the effects of online resistance training on anthropometric parameters and muscular strength (MS) in overweight female adolescents. This prospective, single-center, single-blinded, randomized controlled study included 60 overweight female adolescents who were divided into a control group (n=30) and an intervention group (n=30). The intervention group performed online resistance training, which focused on body weight training of 12 components (4 sets, 12 repetitions) for 45 min, three times per week, for 12 weeks. The intensity of training was 65–75%. Anthropometric parameters, including body weight (BW), body mass index (BMI), body circumference measurements (BCM), and muscle strength (MS), were assessed. All parameters were measured at weeks 0, 8, and 12. Within-group and between-group comparisons were performed. The results revealed improvements in MS, BW, BMI, and BCM in the intervention group. However, chest circumference was not significant. These findings suggest that online resistance training was effective in improving MS and reducing the body composition and circumference.

Carbon dots are carbon based nanoparticles, which have the characteristics of simple preparation process, photoluminescence, biocompatibility, adjustable surface function, water solubility, and low toxicity. They are widely used in biological applications such as imaging, biosensing, photocatalysis, and molecular transfer. It has also aroused great interest among researchers in agriculture and has made significant progress in improving crop growth and production. This review presents the physiological functions of carbon dots for crop growth and development, photosynthesis, water and nutrient absorption, and abiotic stress resistance and their applications in improving ecological environment and agriculture as biosensors, and the future application prospects and research directions of carbon dots in agriculture were prospected.

Nutrients are the driving force of plant and herbivore interactions. Different elements and fertilization levels in soil, or artificially fertilized substrates can have a direct impact on plant defense responses. Meanwhile, nutrient levels mediated by root associated microbes can indirectly affect plant-herbivore interactions. Nutrient uptake promoted by beneficial mycorrhizal fungi or rhizobacteria interacting with roots can stimulate plant tolerance to herbivore attack, as evidenced by herbivore performance, plant nutrient status, plant biomass allocation and compensatory growth. In return, herbivory affects nutrient fluxes between plants and their associated beneficial microbes. Furthermore, aboveground and belowground herbivory can affect the nutrient exchange between plants and soil microbial communities, mainly for carbon-and nitrogen-based resources supporting herbivores´ life cycles. These ecological interactions are governed by jasmonic acid (JA) and key enzymes on the molecular level. This review summarizes the current scientific literature on the role of nutrients in plant-herbivore interactions. This will support efforts to optimize plant defense strategy via managing nutrient variance.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although prognosis continually improved along years, a significant proportion of patients still relapse from the disease due to leukemia resistance to therapy. Methotrexate (MTX), a folic acid antagonist, is a chemotherapy agent commonly used against ALL and a immune-system suppressant for rheumatoid arthritis, that presents multiple and complex mechanisms of action and resistance. Previous studies have shown that MTX modulates the nuclear factor kappa B (NF-κB) pathway, an important family of transcription factors involved in inflammation, immunity, cell survival, and proliferation, frequently hyperactivated in ALL. Using gene set enrichment analysis (GSEA) on publicly available gene expression data from 161 newly diagnosed pediatric ALL patients, we found “TNF-α signaling pathway” to be the most enriched Cancer Hallmark in MTX poor responder patients. Transcriptomic analysis in a panel of ALL cell lines (6 BCP-ALL and 7 T-ALL) also identified the same pathway as differentially enriched among MTX resistant cell lines, as well as in slowly dividing cells. To better understand the crosstalk between NF-κB activity and MTX resistance, we genetically modified the cell lines to express luciferase under a NF-κB biding site promoter. We observed that the fold change in NF-κB activity triggered by TNF-α (but not MTX) treatment correlated with MTX resistance and proliferation across the lines. At the individual gene level, NFKB1 expression was directly associated with a poorer clinical response to MTX, and with both an increased TNF-α-triggered NF-κB activation and MTX resistance in the cell lines. Despite these results, pharmacological inhibition (with BAY 11-7082 and parthenolide) or stimulation (with exogenous TNF-α supplementation) of the NF-κB pathway did not alter MTX resistance of the cell lines significantly, evidencing a complex interplay between MTX and NF-κB in ALL.

Over the past several decades, the extensive use of pyrethroids has led to the development of resistance in many insect populations, including the economically damaging pest tarnished plant bug (TPB), Lygus lineolaris on cotton. To manage TPB resistance, several commercially formulated pyrethroid-containing binary mixtures, in combination with neonicotinoids or avermectin are recommended for TPB control and resistance management in the Mid-south USA. This study aimed to evaluate the toxicity and resistance risks of four formulated pyrethroid-containing binary mixtures (Endigo, Leverage, Athena, and Hero) on one susceptible and two resistant TPB populations which were field-collected in July (Field-R1) and October (Field-R2), respectively. Based on LC50 values, both resistant TPB populations displayed variable tolerance to the four binary mixtures, with Hero showing the highest resistance and Athena the lowest. Notably, the Field-R2 exhibited 1.5-3-fold higher resistance compared to the Field-R1 for all four binary insecticides. Moreover, both resistant TPB populations demonstrated significantly higher resistance ratios toward Hero and Leverage compared to their corresponding individual pyrethroid, while Endigo and Athena showed similar or lower resistance. This study also utilized the calculated additive index (AI) and co-toxicity coefficient (CTC) analysis, which revealed that the two individual components in Leverage exhibited antagonist effects against the two resistant TPB populations. In contrast, the two individual components in Endigo, Hero and Athena displayed synergistic interactions. Considering that Hero is a mixture of two pyrethroids which can enhance the development of TPB resistance, our findings suggest that Endigo and Athena are likely superior products for slowing down resistance development in TPB populations. This study provides valuable insight for selecting the most effective mixtures to achieve better TPB control through synergistic toxicity analysis, while simultaneously reducing economic and environmental risks associated with resistance development in the insect pest.

Chinese pepper rust is a live parasitic fungal disease caused by Coleosporium zanthoxyli, which seriously affects the cultivation and industrial development of Z. armatum. Cultivating and planting resistant cultivars is considered the most economical and environmentally friendly strategy to control this disease. Therefore, the mining of excellent genes for rust resistance and analysis of the mechanism of rust resistance are the key strategies to achieve the targeted breeding of rust resistance. However, there is no relevant report on pepper rust resistance at present. The aim of the present study was to further explore the resistance mechanism of pepper by screening the rust-resistant germplasm resources in the early stage. Combined with the analysis of plant pathology, transcriptomics, and metabolomics, we found that the genes and metabolites related to phenylpropanoid metabolism were highly enriched in resistant varieties after pathogen infection, which indicated that phenylpropanoid metabolism might mediate the resistance of Z. armatum. This finding was further confirmed by real-time quantitative polymerase chain reaction analysis, which revealed that the expression levels of core genes involved in phenylpropane metabolism in disease-resistant varieties were high. In addition, the difference in flavonoid content in the leaves between resistant and susceptible varieties further supported the conclusion that the flavonoid pathway is one of the main pathways involved in resistance formation in Chinese pepper, and MeJA is involved in the formation of resistance. Our research results not only help to better understand the resistance mechanism of Z. armatum rust but also contribute to the breeding and utilization of resistant varieties.

Lodging is one of the important factors affecting the high and stable yield of wheat worldwide. Solid-stemmed wheat has higher stem strength and lodging resistance than hollow-stemmed wheat. There are many solid stemmed varieties, landraces and old varieties of durum wheat. However, the transfer of solid stem genes from durum wheat is suppressed by the suppressor gene located on chromosome 3D in common wheat, and only hollow-stemmed lines have been created. However, synthetic hexaploid wheat can serve as a bridge to transfer solid stem genes from tetraploid wheat to common wheat. In this study, the F1, F2, and F2:3 generations of the cross between solid-stemmed Syn-SAU-119 and semisolid-stemmed Syn-SAU-117 were developed. A single dominant gene, tentatively designated Su-TdDof, was identified in synthetic hexaploid wheat Syn-SAU-117 by genetic analysis, which suppresses stem solidity. Using bulked segregant RNA-seq (BSR-seq) analysis, Su-TdDof was mapped to chromosome 7DS and flanked by markers KASP-669 and KASP-1055 within a 4.53 cM genetic interval corresponding to 3.86 Mb and 2.29Mb physical region in the Chinese Spring (IWGSC RefSeq v1.1) and Ae. tauschii (AL8/78 v4.0) genome, respectively, in which three genes related to solid stem development were annotated. Su-TdDof differed from a previously reported solid stem suppressor gene based on its origin and position. Su-TdDof would provide a valuable example for research on the suppression phenomenon. The flanking markers developed in this study would be useful for screening Ae. tauschii accessions with no suppressor gene (Su-TdDof) to develop more synthetic hexaploid wheat lines for wheat lodging resistance breeding and further cloning the suppressor gene Su-TdDof.

Our ability to cure common diseases is still in danger due to the creation and spread of bacteria and fungi that are resistant to drugs and has developed new resistance mechanisms. The increasing global expansion of multi- and pan-resistant bacteria commonly referred to as "superbugs," which cause diseases that cannot be treated with current antimicrobial medications like antibiotics, is particularly concerning. Indirect and direct risks to public health are posed by microorganisms that are resistant to antibiotics in food. Food can get contaminated via cross-contamination, intentionally introducing resistance genes during food preparation, and antibiotic-resistant bacteria in food. Consuming unprocessed or unpreserved food products increases the danger of transferring antimicrobial resistance to people and other animals. Stressed cells in food can have an impact on food quality, safety, and security. They can also contribute to the development of resistance and afterwards spread it to unintended organisms in the food chain. These reviews look at a variety of topics to address the question of how antimicrobial resistance mechanisms work. The various types of bacteria that make up infections are examined, as well as the usage of antimicrobial agents and the requirement for alternative antimicrobial agents that will discourage the use of synthetic antimicrobial agents. Additionally, specific details are provided regarding the uniqueness, interdependence, and phylogenicity of organisms as well as their interactions with various ecological media. Thus, it is clear why it is important to work with food producers and handlers to stop the spread of pathogenic organisms.

New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with emergence of resistance resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies, that are clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers and phages. Clinical diagnostics optimizes the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious disease include detection, monitoring of response and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives into the use of alternate therapeutics with a particular focus on companion diagnostic applications in infectious diseases.

Bacterial biofilms can cause widespread infection. In addition to causing urinary tract infections and pulmonary infections in patients with cystic fibrosis, biofilms can help microorganisms adhere to the surfaces of various medical devices, causing biofilm-associated infections on the surfaces of biomaterials such as venous ducts, joint prostheses, mechanical heart valves, and catheters. Biofilms provide a protective barrier for bacteria and provide resistance to antimicrobial agents, which increases the morbidity and mortality of patients. This review introduces the formation process and drug resistance mechanism of biofilms in detail, and further summarizes the main characteristics of clinical persistent infection caused by biofilms and the many methods of treating biomaterial-related biofilm. This provides ideas and directions for the development of new biofilm infection strategies related to therapeutic materials.

Weeds that infest crops are a primary factor limiting agricultural productivity world-wide. Weedy rice, also called red rice, has experienced independent evolutionary events through gene flow from wild rice relatives and de-domestication from cultivated rice. Each evolutionary event supplied/equipped weedy rice with competitive abilities that allowed it to thrive with cultivated rice and severely reduce yields in rice fields. Under-standing how competitiveness evolves is important not only for noxious agricultural weed management but also for the transfer of weedy rice traits to cultivated rice. Molec-ular studies of weedy rice using simple sequence repeat (SSR), restriction fragment length polymorphism (RFLP) and whole genome sequence have shown great genetic variations in weedy rice population globally. These variations are evident both at whole genome and at single allele level, including Sh4 (shattering), Hd1 (heading and flower-ing), and Rc (pericarp pigmentation). The goal of this review is to describe the genetic diversity of current weedy rice germplasm and the significance of weedy rice germplasm as a novel source of disease resistance. Understanding these variations, es-pecially at an allelic level, is also crucial as individual locus that control important traits can be of great target to rice breeders.

Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates are one of the most difficult pathogens to treat. Cefiderocol, a chlorocatechol-substituted siderophore antibiotic, was approved by the U.S. Food and Drug Administration (FDA) in 2019 indicated for the treatment of infections due to CRAB infections. Despite the initial positive treatment outcomes with this antimicrobial, recent studies reported higher than all-cause mortality rate in patients treated with cefiderocol. The cause(s) behind these outcomes remains unconfirmed. A plausible hypothesis is heteroresistance, a phenotype characterized by the survival of a small proportion of cells in a population seemingly isogenic. Recent results have shown that the addition of human fluids to CRAB cultures leads to cefiderocol heteroresistance. Here we describe molecular and phenotypic analyses of CRAB heteroresistant bacterial subpopulations to better understand the nature of the less-than-expected successful outcomes after cefiderocol treatment. Methods: Isolation of heteroresistant variants of the CRAB strain AMA40 was carried out in cultures supplemented with cefiderocol and human pleural fluid (HPF). Two AMA40 variants, AMA40 IHC1 and IHC2, were subjected to whole genome sequencing and transcriptional analysis to identify mutations and expression changes associated with cefiderocol heteroresistance. The impact of these mutations on the pharmacodynamic activity of cefiderocol was assessed via susceptibility testing, EDTA and boronic acid inhibition analysis, biofilm formation, and static time-kill assays. Results: Heteroresistant variants AMA40 IHC1 and AMA40 IHC2 have 53 chromosomal mutations, of which 40 are common to both strains. None of the mutations occurred in genes associated with high affinity iron-uptake systems or β-lactam resistance. However, transcriptional analyses showed significant modifications in levels of expression of genes associated with these functions. The blaNDM-1 and blaADC-2, as well as various iron-uptake system genes, were expressed at higher levels than the parental strain. On the other hand, the carO and ompA genes’ expression was reduced. One of the mutations common to both heteroresistant strains mapped within pipA, a gene associated with iron homeostasis in other species. Static time-kill assays showed that supplementing cation-adjusted Mueller-Hinton broth with human serum albumin, the main protein component of HPF, considerably reduced cefiderocol killing activity for all three strains tested. Notably, collateral resistance to amikacin was observed in both variants. Conclusions: We conclude that exposing CRAB to fluids containing high HSA facilitates the rise of heteroresistance associated with point mutations and upregulation of genes coding for β-lactamases and biofilm formation.

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

The aim of this study was to verify the effects of blood flow restriction on movement velocity and muscle activity during the back-squat exercise. Methods: Twenty-four university students participated in this study. In two randomized 72-hours apart sessions, participants performed a 4-set protocol consisting of 30-15-15-15 repetitions performed at 30% of their one-repetition maximum in the back-squat exercise. In both sessions, neuromuscular function was monitored by surface electromyography (EMG) and movement velocity (mean propulsive velocity [MPV], peak concentric velocity [Vmax] and the effort index [EI]). Blood flow restriction (BFR) was applied during exercise in one of the experimental sessions with 80% of full arterial occlusion pressure over lower limbs. Results: BFR condition showed higher (p&lt;0.05) EI, peak and rooted mean square normalized EMG in set 1 compared to set 2. Similar MPV and Vmax were observed at each set for both BFR and control conditions. No significant differences were observed between conditions at any set. Conclusions: BFR did not imply changes in neuromuscular performance during low-intensity resistance training, but it might induce greater intra-series velocity loss and less activation of the muscles involved.

Coronavirus disease 2019 (COVID-19) is a potentially serious acute respiratory infection caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since the World Health Organization (WHO) declared COVID-19 a global pandemic, the virus has spread to more than 200 countries with more than 500 million cases and more than 6 million deaths reported globally. It has long been known that viral respiratory tract infections predispose patients to bacterial infections and that these co-infections often have an unfavourable clinical outcome. Moreover, nosocomial infections, also known as health care-associated infections (HAIs), are those infections that are absent at the time of admission and acquired after hospitalization. However, the impact of coinfections or secondary infections on the progression of COVID-19 disease and its lethal outcome is still debated. The aim of this review was to assess the literature on the incidence of bacterial co-infections and superinfections in patients with COVID-19. The review also highlights the importance of the rational use of antibiotics in patients with COVID-19 and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, alternative antimicrobial agents to counter the emergence of multidrug-resistant bacteria causing healthcare-associated infections in COVID-19 patients will also be discussed.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.

This work highlights that monitoring the microbiological quality of animal products, such as raw sheep’s milk and cheese, is necessary for food safety. Sheep’s milk and its derivatives are not legislated in Brazil. Thus, present study aimed to evaluate: (i) the hygienic-sanitary quality of raw sheep’s milk and cheese produced in southern Brazil; (ii) the presence of enterotoxins and Staphylococcus spp. in these products; and (iii) the antimicrobial susceptibility profile and resistance genes of the isolated Staphylococcus spp. Thirty-five raw sheep’s milk and cheese samples were evaluated. Microbiological quality and the presence of enterotoxins were determined by Petrifilm and VIDAS SET2 methods, respectively. Antimicrobial susceptibility tests were conducted using VITEK 2 equipment and the disc diffusion method. The presence of resistance genes tet(L), sul1, sul2, ermB, tetM, AAC(6)', tetW, and strA were evaluated by PCR. In total, 39 Staphylococcus spp. were isolated. The tetM, ermB, strA, tetL, sul1, AAC(6)’, and sul2 resistance genes were detected in 82%, 59%, 36%, 28%, 23%, 3%, and 3% of isolates, respectively. The results showed that both products contained Staphylococcus spp. and these strains were resistant to antimicrobials as well carriers of resistance genes. These results highlight Brazil's need for specific legislation regarding the pro-duction and marketing of these products.

Long non-coding RNAs (LncRNAs) are mRNA-like molecules that do not encode for proteins and that are longer than 200 nucleotides. LncRNAs play important biological roles in normal cell physiology and organism development. Therefore, deregulation of their activities is involved in disease processes such as cancer. Lung cancer is the leading cause of cancer-related deaths due to late stage at diagnosis, distant metastasis, and high rates of therapeutic failure. LncRNAs are emerging as important molecules in lung cancer for their oncogenic or tumor suppressive functions. LncRNAs are highly stable in circulation, presenting an opportunity for use as non-invasive and early-stage cancer diagnostic tools. Here, we summarize latest works providing in vivo evidence available for LncRNAs role in cancer development, therapy-induced resistance, and their potential as biomarkers for diagnosis and prognosis, with a focus on lung cancer. Additionally, we discuss current therapeutic approaches to target LncRNAs. The evidence discussed here strongly suggests that investigation of LncRNAs in lung cancer in addition to protein-coding genes will provide a holistic view of molecular mechanisms of cancer initiation, development, and progression, and could open a new avenue for cancer treatment.

This paper describes methods for evaluating the thermal properties of textile materials, clothing composites, and clothing using an integrated measurement system that includes a hot plate, a multi-purpose differential conductometer, a thermal manikin, a temperature gradient measurement device, and a device for measuring the physiological parameters of the human body during the exact evaluation of garment thermal comfort. In practice, measurements were taken on four types of materials widely used in the production of conventional and protective clothing. The measurements were carried out using a hot plate and a multi-purpose differential conductometer, determining the thermal resistances of the material in its uncompressed form and a force that was ten times greater than that needed to determine its thickness. Using a hot plate and a multi-purpose differential conductometer, thermal resistances of textile materials were assessed at different levels of material compression. On hot plates, both conduction and convection had an impact on thermal resistance, but in multi-purpose differential conductometer, only conduction did. Moreover, the reduction of thermal resistance was observed while compressing textile materials.

The multidrug-resistant fungal pathogens belonging to the Candida haemulonii complex and the phylogenetically related species Candida auris are well-known for causing infections that are difficult to treat due to their multidrug-resistance profile. C. auris is even more worrisome due to its ability to cause outbreaks in healthcare settings. These emerging yeasts produce a wide range of virulence factors that facilitate the development of the infectious process. In recent years, the aggregative phenotype has been receiving attention, as it is mainly associated with defects in cellular division and its possible involvement in helping the fungus to escape from host immune responses. In this study, we initially investigated the aggregation ability of 18 clinical isolates belonging to the C. haemulonii species complex and C. auris. Subsequently, we evaluated the effects of physicochemical factors on the fungal aggregation competence. The results demonstrated that cell aggregation was a typically time-dependent event, in which almost all studied fungal isolates exhibited high aggregation after 2 h of incubation at 37°C. The aggregation was not impacted by pH, temperature, -mercaptoethanol (a protein-denaturing agent) and EDTA (a chelator agent). Conversely, proteinase K, trypsin and sodium dodecyl sulfate significantly diminished the aggregation. Collectively, our results demonstrated that the aggregation ability in these opportunistic yeast pathogens is time-dependent, and surface proteins and hydrophobic interactions seem to mediate cell aggregation, since the presence of proteases and anionic detergent affected the aggregation ability. However, further studies are necessary to better elucidate this phenomenon.

Ca2+ is a crucial second messenger in plant cells, playing a vital role in various physiological and biochemical processes, including plant growth and development, photosynthesis, and enzyme regulation. Exogenous calcium concentration can have different effects on plant growth. This study aimed to investigate the optimal calcium concentration for the growth of four tree species, namely Pinus tabuliformis, Pinus sylvestris var. mongolica, Populus, and Morus alba seedlings, and whether the optimal calcium concentration varies among different tree species. The study utilized five calcium concentration gradients (0, 100, 200, 400, 800 mg·kg-1) for each species with three repeated treatments. Various growth indexes, photosynthetic parameters, chlorophyll fluorescence parameters, water use efficiency, and antioxidant enzyme activities were assessed to determine each species' calcium concentration requirements. The results showed that exogenous calcium significantly affected the growth and development of each seedling. The growth, biomass, photosynthetic parameters, photosynthetic products, photosynthetic pigments, water use efficiency, and antioxidant enzyme activity all increased initially and then decreased with increasing calcium concentration. Leaf calcium concentration also increased with the exogenous calcium content. Thus, there is an optimal calcium concentration for plant growth, and high or low calcium concentration is not conducive to plant growth. Furthermore, the study found that different tree species have varying optimal calcium concentrations. The optimal calcium concentration for Pinus tabuliformis, Pinus sylvestris var. mongolica, Populus, and Morus alba seedlings was 100, 100, 200, and 400 mg·kg-1, respectively. Finally, the study revealed that broadleaf species require higher calcium concentrations than coniferous species.

Background: The AWaRe tool was set up by the World Health Organization (WHO) to promote the rational use of antimicrobials. Indeed, this tool classifies antibiotics into four groups, Access, Watch, Reserve and not-recommended antibiotics. In Republic Democratic of Congo, data on antibiotic dispensing (prescribing) by health professionals according to the AWaRe classification are scarce. In this research work, we aimed to explore antibiotic dispensing pattern from health professionals according to the WHO AWaRe classification to strengthen the national antimicrobial resistance plan. Methods: For this purpose, a survey was conducted from July to December 2022 in the district of Tshangu in Kinshasa. From randomly selected drugstores, drug-sellers were interviewed and randomly selected customers attending those drugstores were included in the study for medical prescriptions collection. The prescribed antibiotics were classified into the Access, Watch, Reserve and not recommended antibiotics group and by antibiotics number by prescription among pharmacies surveyed. Results: Of 400 medical prescriptions collected, 301 (75.25%) contained antibiotics. Of 301 prescriptions containing antibiotics, 164 (164/301; 54.5%) contained one antibiotic, 117 (117/301; 38.9%) two antibiotics, 15 (15/301; 5%) three antibiotics and 5 (5/301; 1.6%) 4 antibiotics. Out of the total of 463 antibiotics prescribed, 169 (169/463; 36.5%) were from the Access group, 200 (200/463; 43.2%) from the Watch group and 94 (94/463; 20.3%) from not recommended antibiotics group, respectively. Based on the anatomical, therapeutic and chemical (ATC) classification, it can be seen that third generation cephalosporins contained 34.33% of the prescribed antibiotics, followed by penicillins 17.17%, macrolides 7.63%, aminoglycosides 7. 36% and Imidazoles 7.36%, thus accounting approximately for 74% of the classes of antibiotics prescribed. Of the 463 antibiotics prescribed, the most frequently prescribed antibiotics were Ceftriaxone (21.38%), Amoxicillin (11.01%), Gentamycin (5.61%), Amoxicillin-clavulanic acid (5 .61%), Azithromycin (4.97%) and Metronidazole (4.75%), thus accounting for approximately 54% of all antibiotics prescribed. Conclusion: These results highlight the importance of strict implementation of the national plan to combat antimicrobial resistance and the need to train health workers in the correct application of the WHO AWaRe classification.

The antibody Trastuzumab (Tz) targeting ERBB2 has improved the prognosis of patients with breast cancer (BCa) that overexpress this receptor. Resistance to Tz negatively impacts prognosis. Several mechanisms have been reported to cause Tz resistance. The objective of this study was to identify common mechanisms in in vitro models of acquired BCa Tz resistance. In particular, we used three widely available ERBB2+ BCa cell lines adapted to grow in Tz. We performed several analyses to address possible changes in phenotype, proliferation, and ERBB2 membrane expres-sion common to the three Tz-R cell lines compared to wt, but none was found. High-resolution mass spectrometry analysis identified, instead, a common set of differentially expressed proteins (DEPs) in Tz-R vs. wt cells. Furthermore, bioinformatic tools revealed that all three Tz-R cell models shared a modulation of proteins involved in the metabolism of lipids, organophosphate biosynthetic process, and macromolecule methylation. Ultrastructural analysis confirmed altera-tion of lipid droplets in resistant cells. Our data strongly support the hypothesis that complex metabolic adaptation, including lipid metabolism, protein phosphorylation, and possibly chro-matin remodeling, may fuel Tz resistance. The identification of a common set of 10 DEPs in all three TZ-resistant cell lines may provide novel targets for therapeutic intervention.

conclusions. The blends of ultrahigh molecular weight polyethylene/polypropylene (UHMWPE/PP) possess excellent processability, but limited by its reduced mechnical properties. Herein, the high mechanical properties and wear—resistance UHMWPE/PP composites were fabricated by the addition of silicon carbide (SiC) nanoparticles under a consecutive elongational flow without any other additives or solvents. The morphology and thermal properties, mechanical properties, wear resistance as well as scratch resistance of UHMWPE/PP/SiC composites were investigated . The mechanical properties and friction resistance of composites increase initially then decrease with the increase content of SiC. The optimum mechanical properties of UHMWPE/PP/SiC composites are achieved when the content of SiC is 3 phr. In addition, both the hardness and scratch resistance of composites improved upon increasing the content of SiC. These improved mechanical properties and wear resistance originate from the well disperison of SiC nanoparticles along with favourable interfacial adhesive under a consecutive elongational flow.

The emergence of drug resistant pathogenic bacteria is increasingly challenging conventional antibiotics. Plant derived flavonoids are considered as potential alternatives to antibiotics due to their antimicrobial properties. However, the mechanisms by which flavonoids modulate pathogenic microorganisms’ growth are not fully understood. In our previous studies we found that Rutin, a kind of flavonoids showed inhibition against Klebsiella pneumoniae strains. In order to better understand its inhibitory mechanism on strain growth, we used both Rutin and Luteolin as treatments to incubate K. pneumoniae ATCC700603 strain. After incubation for 4 hours, the homogenous and differential effects of two different flavonoids on the growth of K. pneumoniae were evaluated. The integrated metabolomic and transcriptomic analysis was performed. The expression levels of 5,483 genes and the contents of 882 metabolites were measured. The differentially expressed genes (DEGs) and metabolites (DEMs) were screened and analyzed. The correlation between DEGs and DEMs were also studied. Our results showed that Rutin could inhibit the strain growth by changing metabolic pathways and ABC transporters pathways. Our study also revealed FU841_RS17580 and FU841_RS19145 as functional genes that played vital roles in the strain growth.

The article presents the results of a morpho-physiological assessment of rice samples by the strength of growth, as well as an assessment of the degree of development of the conducting system of the flag leaves of rice plants. The resistance of varieties to flooding is very relevant in the fight against weeds due to the deep layer of water that weeds cannot overcome. Currently, there are no zoned varieties in Russia that would meet these requirements. Therefore, the problem of creating such rice varieties is urgent, as it will reduce production costs, reduce grain losses during harvesting, improve the quality of the products obtained, and also reduce the pesticide load on the ecosystem. As a result of research, a number of studied samples revealed the potential to quickly lengthen the first leaves, overcome a large layer of water and accumulate vegetative mass. As a result of the evaluation of the conducting system of the flag leaf of rice plants, it was found that in plants with the flood resistance gene Sub1A, which stops growth under water, the conductive beams were smaller in comparison with other fast-growing samples with the AG, Sk genes. Consequently, fast-growing samples have bigger sizes of the conducting system as a resistance mechanism.

Antibiotic resistance (ABR) is concerning issue due to its direct and indirect repercusions on public health, since decreased therapeutic effect of certain antibiotic to treatment complications that can cause death. There are several mechanism as to how ABR can be transferred from one microoorganisms to another, and many of them are dependant many environmental factors. The food supply chain is a environment in which ABR gene transfer can occur is multiple pathways, which generate concerns regarding food safety. Here, we summarize relevant mechanisms which are implied in ABR in food supply chain but also we are addressing routes of transmission and prevalence of ABR, implications on public health, and the application of new alternatives to antibiotics such as antimicrobial peptides, mainly bacteriocins, in order to countermeasure ABR.

Assessing the genetic diversity of metabolic resistance genes such as cytochrome P450s helps to understand the dynamics and evolution of resistance in the field. Here, we analysed the polymor-phisms of CYP6M2 and CYP6P4 associated with pyrethroid resistance in Anopheles coluzzii and An. gambiae, to detect potential resistance markers. Field-caught resistant mosquitoes and susceptible lab-strains were crossed and F4 was exposed to permethrin for 15min and 90min to discriminate highly susceptible (HS) and highly resistant (HR) mosquitoes respectively. Significant permethrin mortality reduction was observed after pre-exposure to PBO, suggesting P450s genes involvement. QPCR analysis revealed significant over-expression of CYP6M2 (FC=19.57 [95%CI 13.96-25.18] for An. coluzzii; 10.16 [7.86-12.46] for An. gambiae) and CYP6P4 (FC=6.73 [6.15-7.30] An. coluzzii; 23.62 [26.48-20.76] An. gambiae). Full-gene and ≈1kb upstream were sequenced. For CYP6M2, upstream region shows low diversity in HR and HS (overall Hd=0.49, π=0.018), whereas the full-gene shows allelic-variation but without evidence of ongoing selection. CYP6P4 upstream region showed a lower diversity in HR (Hd=0.48) than HS (Hd=0.86) of An. gambiae. These results highlighted that CYP6P4-associated resistance is potentially driven by modification in upstream region. However further work is needed to determine the real causative variants which will help design rapid detec-tion tools.

As a result of the COVID-19 pandemic, as well as other outbreaks such as SARS and Ebola, bats are recognized as a critical species for mediating zoonotic infectious disease spillover events. While there is a growing concern of increased antimicrobial resistance (AMR) globally during this pandemic, knowledge of AMR circulating between bats and humans is limited. In this paper, we have reviewed the evidence of AMR in bats and discussed the planetary health aspect of AMR to elucidate how this is associated with the emergence, spread and persistence of antibiotic resistance at the human-animal interface. The presence of clinically significant resistant bacteria in bats and wild life has reflective and broad impact on zoonotic pandemic surveillance, disease transmission and treatment modalities. We searched MEDLINE through PubMed and Google Scholar to retrieve relevant studies (n=38) that provided data on resistant bacteria in bats till September 30, 2022. There is a substantial variability in the results from studies measuring the prevalence of AMR based on geographic location, bat types and time. We found all major groups of gram positive and gram negative bacteria in bats which are resistant to commonly used antibiotics. The most alarming issue is- recent studies have increasingly identified Methicillin Resistant Staphylococcus aureus (MRSA), ESBL producing and Colistin resistant Enterobacteriaceae in samples from bats. This evidence of superbugs abundance in both humans and wild mammals like bats, could facilitate a greater understanding of which specific pathways of exposure should be targeted. We believe that these data will also facilitate future pandemic prepareness as well as global AMR containment during the pandemic events and beyond.

The discovery of first ATP-binding cassette (ABC) transporter, whose overexpression in cancer cells is responsible for exporting anticancer drugs out of tumor cells, initiated enormous efforts to overcome tumor cell multidrug resistance (MDR) by inhibition of ABC-transporter. Because of its many physiological functions, diverse studies have been conducted on the mechanism, function and regulation of this important group of transmembrane transport proteins. In this review, we will focus on the structural aspects of this transporter superfamily. Since the resolution revolution of electron microscope, experimentally solved structures increased rapidly. A summary of the structures available and an overview of recent structure-based studies are provided. More specifically, the artificial intelligence (AI)-based predictions from AlphaFold 2 will be discussed.

The synergistic effect of silicon and cerium addition on the oxidation resistance of pack cementation aluminide coating applied on Ni-based superalloy substrate was investigated. The effect of cerium and silicon on the scale morphology, oxidation behavior, and scale spallation tendency are discussed based on the experimental results, using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray analyses (EDX). In addition, the oxidation resistance was evaluated by measuring the weight of samples after each 16-hour cycle at 1100˚C for 50 cycles. The experiments indicated that silicon addition to aluminide coating improves the oxidation resistance through the formation of β-NiAl1-nSin and δ-Ni2Al3-nSin and δ-Ni2Si phases. Furthermore, the addition of 1% cerium to modified aluminide enhances the formation of the fine-grained microstructure of the β-NiAl and δ-Ni2Al3 and reduces the outward/inward diffusion of elements (so-called blocking effect) which significantly modifies the hot oxidation resistance. The addition of 2% cerium, owing to the distortion of the β-NiAl and δ-Ni2Al3 phases, strictly decreases the hot oxidation resistance and the coating is exfoliated after 450 h at 1100 °C. The cyclic oxidation tests showed that the samples containing 1% cerium and 6% silicon possess the highest hot oxidation resistance in which 2 mg/cm2 weight loss of Ce-Si-aluminide was reported after 800 h. This is attributed to the simultaneous effect of cerium and silicon during the deposition process which reduces the oxygen diffusion and reduces the growth rate of α-Al2O3 during oxidation tests. The α-Al2O3 oxidation layer morphology showed that finer grains are formed in samples containing optimum ratios of cerium and silicon which indicates that these elements improve the coating adhesion and oxidation resistance simultaneously.

Antimicrobial resistance (AMR) due to community carriage of antibiotic-resistant bacteria is highly prevalent in the WHO South-East Asia region. One of the major reasons is the misuse of antibiotics in animal farming practices and at community level, which threatens both human and animal health. However, this multifaceted One Health (OH) problem of antibiotic use (ABU) in poultry farms and respective farmers is not well studied in countries like Pakistan. Therefore, we conducted n OH cross-sectional study in rural Punjab to explore the current practices of ABU in poultry and poultry farmers, associated factors, their healthcare-seeking behaviour and biosecurity practices. We found all the participating farmers using antibiotics for poultry, 60% of which were Colistin sulphate and Amoxicillin trihydrate. The significant consumption of antibiotics in poultry farms (60%) and poultry farmers (50%) was without prescription. Most of the farms (85%) had no wastewater drainage system, causing direct shedding of poultry waste and antibiotic residue in the surrounding environment. Lack of farmers’ education, professional farm training and duration of farming experience were the significantly associated factors with ABU and knowledge of AMR. Our study implies the necessity of an integrated OH-AMR policy with the inclusion of farmers’ education, mass awareness, and strict antibiotic usage guidelines.

Often yam varieties grown in different agro-ecologies show differential responses across production environments, a term known as genotype-by-environment interaction. Genotype-by-environment interaction makes selecting the best genotypes under varied production environments more complex. This study tested twenty yam genotypes evaluated in six test environments to assess genotype, environment, and the interaction between genotypes and environmental effect for tuber yield, yam mosaic virus, and dry matter content. The experiments were conducted in two seasons across three locations in Uganda using a randomized complete block design with three replications. The results showed a significant effect (p ≤ 0.001) for genotype (G), environment (E), and genotype by environment interaction for all the traits. Serere 2021 and Namulonge 2021 were identified as the most discriminating and representative environments for testing the yam mosaic virus, respectively. Serere 2021 was recognized as the most discriminating environment, whereas Arua 2021 was identified as the closest to an ideal environment for assessing yam tuber yields. The tested genotypes also exhibited high resistance to yam mosaic virus disease, high tuber yields, and high dry matter content. Genotypes UGY16020, UGY16034, UGY16042, and UGY16080 demonstrated great resistance to yam mosaic virus disease, high yielding, and considerable dry matter content and are thus potential parents for yam improvement. Further evaluation of the four genotypes should be done under farmers' production systems for selection, improvement, and release as new yam varieties for Uganda

Background: Nutrient supplements are widely used for type 2 diabetes (T2D) yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycemic control, measures of insulin sensitivity and secretion), adverse events, and GRADE assessments. Quality was assessed using AMSTAR-2. Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C and omega-3 polyunsaturated fatty acids (-3 PUFAs) were superior to placebo for the primary outcome of HbA1c (MD -0.54%, -0.54% and ES -0.27 respectively). Probiotics were superior to placebo for HbA1c (WMD -0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD -0.17%). Magnesium, zinc, Vitamin C, probiotics and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.

Multicomponent reactions (MCR) have been used to synthesis a wide range of analogs from several classes of heterocyclic compounds, with multifaceted medicinal uses. The synthesis of highly functionalized molecules in a single pot is a unique property of MCR, allowing researchers to quickly assemble libraries of compounds of biological interest and uncover novel leads as possible therapeutic agents. Isocyanide-based multicomponent reactions have proven to be extremely effective at swiftly specifying members of compound libraries, particularly in discovery of drug . The understanding of structure-activity correlations that drive the development of new goods and technology, requires structural variety in these libraries. In current world, antibiotic resistance is a major ongoing problem which is developing a problematic scenario in public health. The implementation of isocyanide based multicomponent reactions uphold a significant potential in this regard. By utilizing such reactions, new antimicrobial compounds can be discovered and fight against such concerns. This study discusses recent developments in antimicrobial medication discovery using isocyanide-based multicomponent reactions (IMCRs). Furthermore, the article emphasizes the potential of IMCRs in the near future.

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

Resistance to Pyrimethamine, an antimalarial medicine has been reported to be due to mutations in Dihydrofolate reductase-thymidylate synthase (DHFR-TS). Phytochemicals, particularly from plants that been used in ethnomedicine, have been reported to have privileged structures that might bind strongly to the mutants of DHFR-TS. The aim of this study is to identify phytochemicals of Acalypha wilkesiana, Cymbopogon citratus, Azadirachta indica, and Morinda lucida with high binding affinities for the Plasmodium falciparum DHFR-TS. The three-dimensional structures of the phytochemicals, wide type and mutant forms of DHTR-TS were obtained from PubChem and Protein Databank (PDB) respectively. They were appropriately prepared and molecular docking simulations was implemented to predict binding affinities of the phytochemicals to the wildtype and mutant forms of DHTR-TS. Druglikeness assessment was implemented to triage the top binding phytochemicals and molecular dynamics simulations was done to establish the stability of the interaction of the top-ranked phytochemical with one of the mutants of DHFR-TS. Nineteen phytochemicals showed higher binding affinities to both the wild type and mutant forms DHFR-TS than Pyrimethamine. Molecular dynamics revealed that the receptor-ligand binding of luteolin, the top-ranked, drug like phytochemicals, to the quadruple mutant was stable.

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

Resistance spot welding is an established joining process in the production of safety-relevant components in the automotive industry. Therefore, a consecutive process monitoring is essential to meet the high-quality requirements. Artificial neural networks can be used to evaluate the process parameters and signals to ensure the individual spot weld quality. The predictive accuracy of such algorithms depends on the provided training data set and the prediction of untrained data is challenging. The aim of this paper is to investigate the extrapolation capability of the multi-layer perceptron model. That means, that the predictive performance of the model will be tested with data that clearly differs from the training data in terms of material and coating composition. Therefore, three multi-layer perceptron regression models were implemented to predict the nugget diameter from process data. The three models were able to predict the trained datasets very well. The models, which were provided with features from the dynamic resistance curve predicted the new dataset better than the model with only process parameters. This study shows the beneficial influence of the process signals on the predictive accuracy and robustness of artificial neural network algorithms. Especially, when predicting a data set from outside of the training space.

Staphylococcus aureus can develop resistance by mutation, tranfection or biofilm formation. Resistance was induced in S. aureus by growth in sub-inhibitory concentrations of ciprofloxacin for 30 days. The ability of the antimicrobials to disrupt biofilms was determined using crystal violet and live/dead staining. Effects on the cell membranes of biofilm cells was evaluated by measuring release of dyes and ATP and nucleic acids. S. aureus did not develop resistance to the AMPs but resistance increased to ciprofloxacin by 128 times after 30 passages. Only peptides reduced biofilms of ciprofloxacin resistant cells. The antibiofilm effect of melimine with ciprofloxacin was more (27%) than with melimine alone at 1X MIC (p < 0.001). Similarly, at 1X MIC the combination of Mel4 and ciprofloxacin produced more (48%) biofilm disruption than Mel4 alone (p < 0.001). Combinations of either of the peptides with ciprofloxacin at 2X MIC released  66 nM ATP, more than either peptide alone (p  0.005). At 2X MIC, only melimine in combination with ciprofloxacin released DNA/RNA which was 3 times more than released by melimine alone (p = 0.043). These results suggest the potential use of melimine and Mel4 with conventional antibiotics for the treatments of S. aureus biofilms.

The emergence of multi-drug resistant E. coli is an important matter of increasing considerable concern to global public health. The aim of this study was to investigate the incidence, antibiotic resistance pattern, phylogroups and genetic variation of E. coli isolates from raw milk, vegetable salad and ground meat samples. Methods: Culture-based techniques, Kirby-Bauer disk diffusion susceptibility testing, PCR and RAPD assays were used to determine the incidence rate, antimicrobial resistance pattern, phylogenetic groups and genetic diversity of the E. coli isolates. Results: E. coli isolates were highly resistant to amoxicillin (79.16%), trime-thoprim-sulfamethoxazole (70.83%), amoxicillin-clavulanic acid (62.50%), tetracycline (54.16%), chloramphenicol (54.16%), nitrofurantoin (54.16%), ampicillin (45.83%), streptomycin (45.83%), and kanamycin (33.33%); and completely susceptible to norfloxacin and azithromycin. 70.83% of the isolates were multi-drug resistant. Most E. coli isolates (46%) belonged to phylogroup A. RAPD with UBC245 primer categorized the isolates into 11 clusters. A high level of genetic di-versity was found among the isolates; however, 33.3% of the isolates were grouped in a major cluster (R5). Conclusions: Antibiotic resistance patterns are randomly distributed among the ge-netic clusters. Novel, practical, efficient food safety control and surveillance systems of multi-drug resistant foodborne pathogens are required to control the foodborne pathogen contamina-tion.

The aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib] is a common cause of resistance to amikacin and other aminoglycosides in Gram-negatives. Utilization of mixture-based combinatorial libraries and application of the positional scanning strategy identified an inhibitor of AAC(6′)-Ib. This inhibitor’s chemical structure consists of a pyrrolidine pentamine scaffold substituted at four locations (R1, R3, R4, and R5). The substituents are two S-phenyl (R1 and R4), an S-hydroxymethyl (R3), and a 3-phenylbutyl (R5) groups. Another location, R2, does not have a substitution, but it is named because its stereochemistry was modified in some compounds utilized in this study. Structure-activity relationship (SAR) analysis using derivatives with different functionalities, modified stereochemistry, and truncations were carried out by assessing the effect of the addition of each compound at 8 µM to 16 µg/ml amikacin-containing media and performing checkerboard assays varying the concentrations of the inhibitor analogs and the antibiotic. The results showed that: 1) the aromatic functionalities at R1 and R4 are essential, but the stereochemistry is essential only at R4, 2) the stereochemical conformation at R2 is critical, 3) the hydroxyl moiety at R3 as well as stereoconformation are required for full inhibitory activity, 4) the phenyl functionality at R5 is not essential and can be replaced by aliphatic groups, 5) the location of the phenyl group on the butyl carbon chain at R5 is not essential, 6) the length of the aliphatic chain at R5 is not critical, 7) all truncations of the scaffold resulted in inactive compounds. Molecular docking revealed that all compounds preferentially bind to the kanamycin C binding cavity, and binding affinity correlates with the experimental data for most of the compounds evaluated. The SAR results in this study will serve as the basis for the design of new analogs in an effort to improve their ability to induce phenotypic conversion to susceptibility in amikacin-resistant pathogens.

Cancer is one of the leading causes of death and morbidity with a complex pathophysiology. Traditional cancer therapies include chemotherapy, radiation therapy, targeted therapy, and immunotherapy. However, limitations such as lack of specificity, cytotoxicity, and multi-drug resistance pose a substantial challenge for favorable cancer treatment. The advent of nanotechnology has revolutionized the arena of cancer diagnosis and treatment. Nanoparticles (1-100nm) can be used in the treatment of cancer owing to their specific advantages such as biocompatibility, reduced toxicity, more excellent stability, enhanced permeability and retention effect, and precise targeting. Nanoparticles are classified into several main categories. The nanoparticle drug delivery system is particular and utilizes tumor and tumor environment characteristics. Nanoparticles not only solve the limitations of conventional cancer treatment but also overcome multidrug resistance. Additionally, as new multidrug resistance mechanisms are unraveled and studied, nanoparticles are being investigated more vigorously. Various therapeutic implications of nano-formulations have created brand new perspectives for cancer treatment. However, a majority of the research is limited to in vivo and in vitro studies, and the number of nano-drugs that are approved has not much amplified over the years. In this review, we discuss numerous types of nanoparticles, targeting mechanisms along with approved nanotherapeutics for oncological implications in cancer treatment. Further, we also summarize the current perspective, advantages, and challenges in clinical translation.

Gastric cancer, also known as stomach cancer, is a cancer which develops from the lining of the stomach. Accumulated evidences and epidemiological studies have been indicated that natural products play an important role in gastric cancer prevention and treatment, although its mechanism of action did not elucidate yet. Particularly, experimental studies have been showed that natural products displayed a protective effect against gastric cancer via numerous molecular mechanisms such as suppression of cell metastasis, anti-angiogenesis, inhibition of cell proliferation, induction of apoptosis, and modulation of autophagy. Although chemotherapy remains the standard treatment for advanced gastric cancer along with surgery, radiation therapy, hormone therapy and immunotherapy, but its adverse side effects including neutropenia, stomatitis, mucositis, diarrhea, nausea, and emesis are well documented. Additionally, intake of naturally occurring phytochemicals could increase the efficacy of gastric chemotherapy and chemotherapeutics resistance. However, natural product structural stability and powerful bioactivity are important to develop novel treatments for gastric cancer that may minimize such adverse effects. Therefore, the purpose of this review is to summarize the potential therapeutic effects of natural products on prevention and treatment of gastric cancer with intensive molecular mechanisms of action, bioavailability, and safety efficacy.