The effect of ferromagnetic CaMnO3 (CMO) addition on structural, magnetic, dielectric, and ferroelec-tric properties of BiFeO3 are presented. X ray diffraction and Raman investigation allowed the identifi-cation of single pseudo cubic perovskite structure. The magnetic measurement showed that the pre-pared films exhibit a ferromagnetic behavior at low temperature with both coercive field and remnant magnetization increased with increasing CMO content. However, a deterioration of magnetization was observed at room temperature. Ferroelectric study revealed an antiferroelectric like behavior with a pinched P-E hysteresis loop for 5%CMO doping BFO resulting in low remnant polarization and double hysteresis loops. Whereas, high remnant polarization and coercive field with a likely square hysteresis loop are obtained for 10 % CMO addition. Furthermore, a bipolar resistive switching behavior with a threshold voltage of about 1.8V is observed for high doped film that can be linked to the ferroelectric polarization switching.

Transferrin (TF) is a key iron carrier protein. Studies in human cohorts and in cultured adipocytes suggested that decreased transferrin expression and intracellular iron in adipocytes leads to impaired insulin responsiveness and causes differential expression of genes involved in metabolism, insulin action, and obesity. While suggestive, these studies did not definitively prove in an intact organism that altering TF expression in adipocytes is sufficient to affect glucose homeostasis and insulin resistance. In this study we created a mouse model of decreased transferrin expression only in adipocytes (Trf+/-Cre+/-) to test the hypothesis that iron trafficking in adipose tissue is sufficient to affect insulin sensitivity. Area under the glucose curve (AUCg) after intraperitoneal glucose administration was increased in the Trf+/-Cre+/- mice compared to wild type (WT) mice on a normal chow diet, and the mice were slightly heavier (p=0.02 for both). Homeostasis Model of Insulin Resistance (HOMA-IR) values were also significantly higher in the Trf+/- Cre+/- mice (p<0.05). Thus, supporting our hypothesis, analysis of mice with decreased expression of TF restricted to adipocytes showed that a decrease in adipocyte TF is sufficient to affect insulin resistance, weight, and glucose homeostasis.

Vanadium is a well-known essential trace element, which usually exists in oxidation states in form of vanadate cation intracellularly. The pharmacological study of vanadium begins at the discovery of its unexpected inhibitory effect on ATPase. Thereafter, the protective effects on cells and the abilities in glucose metabolism regulation were observed from vanadium compound, leading to the application of vanadium compounds in clinical trials for curing diabetes. Alzheimer’s dis-ease (AD) is the most common dementia disease in elderly people. However, there is still no efficient agents for treating AD safely to date. This is mainly because of the complexity of the pathology, which are characterized by the senile plaques composed by amyloid-beta (Aβ) protein in the parenchyma of brain and the neurofibrillary tangles (NFTs) derived from hyperphosphorylated tau protein in neurocyte, along with mitochondrial damage, and eventually the central nervous system (CNS) atrophy. AD was also illustrated as type-3 diabetes, because of the observations of insulin deficiency and the high level of glucose in cerebrospinal fluid (CSF), as well as the im-paired insulin signaling in brain. In this review, we summarized the advance of applicating vanadium compound on AD treatment in experimental research and pointed out the limitation of the current study on using vanadium compounds in AD treatment. We hope it will help the future study in this field.

Antimicrobial resistance (AMR) has a significant global impact on human, animal, and environmental health. Misuse and overuse of antibiotics in clinical and animal production settings are the main drivers behind the emergence of antimicrobial resistant bacteria. However, other compounds with antimicrobial activity may also contribute to this global public health problem. The aim of this comprehensive review is to provide detailed insights into the impact of metals and organic acids on the emergence and spread of AMR in the food chain, for which their role is not fully understood. The review examines the widespread use of organic acids in the food industry as feed additives or disinfectants, the crucial role of copper in animal growth and the harmful effects of mercury and arsenic as pollutants in food-producing environments. Additionally, it explores the antimicrobial mechanisms of metals and organic acids, the tolerance mechanisms developed by bacteria, and the interplay between genes responsible for metal tolerance and AMR. The comprehensive and integrated data presented highlights the need to further explore and understand the role of metals and organic acids as drivers of AMR to develop well-defined strategies effectively mitigating the AMR crisis within the food chain context.

Ditching-rotary tiller was widely used in tillage and ditching furrow during rapeseed sowing. As its ditching furrow system (consist of four identical ditching plows) would bear great drag resistance from the soil during operation, the ditching plow was optimized based on differential geometry analysis and EDEM simulation. Resistance-velocity simulation indicated the plow with parabolic type guide curve had better reduce-drag characteristics. Differential geometry analysis indicated decay rate of E and growth rate of G could represent the variable regularity of drag resistance with the increase of velocity. The L value could represent the magnitude of drag resistance. The smaller L value, decay rate of E and growth rate of G, the better drag-reduce characteristics. Quadratic rotation orthogonal combination design shown the optimal structural parameter values were: Δθ=15°, θmin=45°, h=250mm, l=100mm. The minimum average drag resistance was 230.1N. The differential geometry analysis of optimal ditching plow shown |dE/dκ| and |dG/dκ| could obtain minimum value, indicating growth rate of drag resistance for optimal plow was the lowest within the experimental level. Field experiment indicated the operation effect of optimized ditching furrow system could met the requirements of rapeseed sowing. The research provided in-depth theoretical guidance for Drag-reduce design of plow.

The emergence of CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, has revolutionized the treatment landscape for hormone receptor-positive breast cancer. These agents have demonstrated significant clinical benefits in terms of both progression-free survival and overall survival. However, resistance to CDK4/6 inhibitors remains a challenge, limiting their long-term efficacy. Understanding the complex mechanisms driving resistance is crucial for the development of novel therapeutic strategies and improvement of patient outcomes. Translational research efforts, such as preclinical models and biomarker studies, offer valuable insight into resistance mechanisms and may guide the identification of novel combination therapies. This review paper aims to outline the reported mechanisms underlying CDK4/6 inhibitor resistance, drawing insights from both clinical data and translational research in order to help direct the future of treatment for hormone receptor positive metastatic breast cancer.

The concept of omics-based technological approaches has promoted translational research by integrating knowledge from diverse areas to understand their dynamics by exploring the molecular mechanisms underlying various processes paving the way for further improvements in the crops quality by providing sound knowledge on controlling plant diseases. This area is not profoundly investigated a decade back and hence this knowledge has become exceedingly important in modern times as it has got potential for being utilized in crop improvement programs. In this review, the contributions of different omics technologies including genomics, transcriptomics, proteomics, and metabolomics in understanding and materializing the ways involved in the plant pathogen interaction (PPI) is discussed. Furthermore, opportunities, challenges, and perspectives of omics linked to signaling mechanisms have also been highlighted that are significantly linked to plant-microbe interactions.

We are living in a business context characterized by change, which today behaves with an unprecedented intensity, driven by the technological revolution and increased competition. As a result, increasingly large and complex companies are facing profound transformation processes in which the role of the human factor and of managers in particular, due to their high capacity to impact the organization, is essential. In response to this reality, the literature has developed a large number of approaches from different areas of knowledge: from business economics to psychology, including technical disciplines. This article offers a classification of these approaches that provides an overview of research on the role of managers in change management.

Acinetobacter baumannii (AB) is a bacterium that causes infections, particularly in immunocompromised patients. Treatment is challenging due to biofilm formation by AB strains, which hinders antibiotic effec-tiveness and promotes drug resistance. The aim of our study was to analyze the biofilm-producing capacity of AB isolates from various forms of infections in relation to biofilm-related genes and their drug resistance. We tested one hundred isolates for biofilm formation using the crystal violet microplate method. Drug re-sistance analyses were performed based on EUCAST and CLSI guidelines, and biofilm genes were detected using PCR. All tested strains were found to form biofilms, with 50% being ICU strains and 72% classified as strong biofilm-producers. Among these, 87% were extensively drug-resistant (XDR) and 2% were extra extensively drug-resistant (E-XDR). The most common gene set was bap, bfmS, csuE, and ompA, found in 57% of all isolates. Our research has shown that, regardless of the form of infection, biofilm-forming strains can be expected among AB isolates. The emergence of E-XDR and XDR strains among non-ICU infections highlights the necessity for the rational use of antibiotics to stop or limit the further acquisition of drug re-sistance by A. baumannii.

Antimicrobial resistance (AMR) is a growing public health concern worldwide, and it poses a significant threat to human, animal, and environmental health. The overuse and misuse of antibiotics have contributed significantly to the emergence and spread of antimicrobial resistance, which may lead to significant economic consequences like reduced productivity and increased healthcare costs. Nanotechnology offers a promising platform for addressing this challenge. Nanoparticles have unique properties that make them highly effective in combating bacterial infections by inhibiting the growth and survival of multidrug-resistant bacteria in three areas of health: human, animal, and environmental. To conduct an economic evaluation of surveillance in this context, it is crucial to have a comprehension of the connections to be addressed by several nations by implementing national action policies based on the One Health strategy. This review provides an overview of the progress made thus far and presents potential future directions to optimize the impact of nanobiotics on AMR.

Japanese apricot (Prunus mume) is a culturally and economically important fruit tree in East Asia. ‘Nanko’, the primary cultivar of the Japanese apricot well known in Japan, usually suffers from scab, a disease caused by Venturia carpophila. Scab results in the development of black spots on the fruit surface, which considerably reduces its commercial value. Despite being an economic concern for Japanese apricot, there have been few reports on the phenotypic variation in scab resistance/susceptibility, the underlying genetic factors, and the development of DNA markers. Therefore, in this study, we performed a comprehensive trait analysis for scab resistance and susceptibility for four years and conducted a genome-wide association study (GWAS) to identify the associated loci. The results showed that significant GWAS peaks were detected in 2017 and 2018. Promising candidate gene encoding domains associated with disease resistance were found at the nine single-nucleotide polymorphisms (SNPs) identified in 2017 and 2018. These SNPs were thought to be associated with scab susceptibility of ‘Nanko’ lineages. These findings shed light on the mechanisms of scab resistance in P. mume and will assist future breeding programs to improve scab resistance in ‘Nanko’ lineages.

The identification of biomarkers is crucial for cancer diagnosis, understanding the underlying biological mechanisms, and developing targeted therapies. In this study we propose a machine learning approach to predict the outcome and platinum resistance status of ovarian cancer patients using public available gene expression data. Six classical machine learning algorithms are compared on their predictive performance. Those with the highest score are analyzed by their feature importance using the SHAP algorithm. We were able to select multiple genes that were correlating with the outcome and platinum resistance status of the patients and validated those using Kaplan-Meier plots. In comparison to similar approaches the performance of the models were higher and different genes using feature importance analysis were identified. The most promising identified genes that could be used as biomarkers are: TMEFF2, ACSM3, SLC4A1 and ALDH4A1.

The aim of this study was to evaluate and compare the fracture resistance of definitive zirconia dioxide restorations obtained using a computer-aided design and manufacturing (CAD/CAM) system. Methods: Two groups of ten samples were analyzed for each material (n: 20), the first group was Zolid Gen X Amann Girrbach (ZGX) and the second group was Cercon HT Dentsply Sirona (CDS). The restorations were designed with identical parameters and milled with a CAD/CAM system. Each specimen was load tested at a speed of 0.5 mm/min with a direction parallel to the major axis of the tooth and with an initial preload of 10N until fracture using a universal testing machine (Universal/Tensile Testing Machine, Autograph AGS-X Series) equipped with a 20 kN load cell. The results obtained were recorded in Newtons (N), using software connected to the testing machine. Results: Statistically significant differences were found, and the fracture toughness of the monolithic zirconia crowns was lower in the CDS group (1744.84 ± 172.8 N), compared to the ZGX group (2387.41 ± 516 N). Conclusions: The monolithic zirconia CAD-CAM zirconia crowns showed sufficient fracture strength to be used in posterior molar and premolar zones with either material as they withstood fracture loads greater than the maximum masticatory force.

Background: Blood flow restriction training (BFRT) uses occlusion during low-intensity resistance training (&lt;50% of repetition maximum, 1RM) to reduce arterial blood flow and venous return, imposing greater metabolic stress but similar muscular hypertrophy and strength gains as high-intensity resistance training (HIRT). However, no study, to date, has incorporated BFRT in a collegiate strength and conditioning setting to assess ecological validity. We aimed to investigate the effects of adding 6-weeks of accessory BFRT or HIRT to NCAA Division III soccer players prescribed resistance training regimen on muscle strength and hypertrophy. Methods: Male and female (n=17) athletes were randomly assigned to complete biceps curls 2x/week under BFRT or control (HIRT), following the regularly scheduled strength training. Bicep strength (1RM) and circumference (BC) were assessed at weeks 0, 3, and 6. Results: In men, no significant interaction between time and condition was observed for BC (p=0.861), though condition (BFRT vs Control, p=0.025) and time (p=0.024) were significant. For 1RM, there was no significant interaction between time and condition (BFRT vs HIRT, p=0.067) or of condition (p=0.598), but there was a significant effect of time (p=0.004). In women, there was no significant interaction between time and condition (p=0.765) or of condition (p=0.971) on BC, but time was significant (p=0.045). For 1RM, there was no significant interaction between time and condition (p=0.227) or of condition (p=0.741), but time was (p=0.018). Conclusion: BFRT induced similar increases in muscle strength and hypertrophy as HIRT in soccer players, suggesting that BFRT could be incorporated into collegiate athlete training.

A novel flexible humidity sensor, incorporating gold nanoparticles (Au NPs) and a trifunctional organosilica compound, has been developed through the integration of sol-gel processing, free radical polymerization, and self-assembly techniques. The trifunctional organosilica was initially synthesized by modifying (3-mercaptopropyl)trimethoxysilane (thiol-MPTMS) with 3-(trimethoxysilyl)propyl methacrylate (vinyl-TMSPMA). Subsequently, a hydrophilic polyelectrolyte, [3(methacryloylamino)propyl]trimethyl ammonium chloride (MAPTAC), was grafted onto the MPTMS-TMSPMA gel. The Au NPs were assembled onto the thiol groups present in the MPTMS-TMSPMA-MAPTAC gel network. The compositional and microstructural properties of the Au NPs/MPTMS-TMSPMA-MAPTAC composite film were investigated utilizing Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The presence of thiol groups and mesoporous silica skeletons ensured the stability of the humidity-sensing film on the substrate under highly humid conditions, while the hydrophilic groups functioned as humidity-sensitive sites. This innovative humidity sensor demonstrated high sensitivity, acceptable linearity, minimal hysteresis, and rapid response time across a broad range of working humidity levels. Based on the complex impedance spectra analysis, hydronium ions (H₃O⁺) were determined to govern the conductance process of the flexible humidity sensor.

Rapid in vitro assessment of antimicrobial drug efficacy under clinically relevant pharmacokinetic conditions is an essential element of both drug development and clinical use. Here we present an overview of a novel integrated methodology for rapid assessment of such efficacy, particularly against emergence of resistant bacterial strains, as jointly researched by the authors in recent years. This methodology enables rapid in vitro assessment of antimicrobial efficacy of a single or multiple drugs in combination, following clinically relevant pharmacokinetics. The proposed methodology entails (a) automated collection of longitudinal time-kill data in an optical-density instrument; (b) processing of collected time-kill data with the aid of a mathematical model to de-termine optimal dosing regimens under clinically relevant pharmacokinetics for a single or mul-tiple drugs; and (c) in vitro validation of promising dosing regimens in a hollow fiber system. Proof-of-concept of this methodology through a number of in vitro studies is discussed. Future directions for refinement of optimal data collection and processing are discussed.

Information about molecular mechanism of pesticide resistance in the rust-red flour beetle, a major pest destroying grains and flour across Nigeria is grossly lacking, hindering evidence-based con-trol. Here, we identified to species level three populations of the red-flour beetle from Kano, Ni-geria, as Tribolium castaneum, and investigated the mechanism driving their insecticide resistance. IRAC susceptibility bioassays established high cypermethrin resistance, with LC50s of 4.35-5.46mg/ml in the three populations, NNFM, R/Zaki and Yankaba. High DDT and malathion resistance was observed in NNFM, with LC50s of 15.32- and 3.71mg/ml, respectively. High sus-ceptibility was observed towards dichlorvos in all three populations with LC50s of 0.17-0.35mg/ml, respectively. Synergist bioassay with piperonylbutoxide significantly restored cypermethrin sus-ceptibility, with mortality increasing almost threefold, from 24.8% obtained from 1.25mg/ml of cypermethrin, to 63.3% in synergised group (p=0.013), suggesting a preeminent role of P450s. The two major knockdown resistance (kdr) mutations, T929I and L1014F in the IIS4 and IIS6 fragments of voltage-gated sodium channel were not detected in both cypermethrin-alive and cyperme-thrin-dead beetles, suggesting lesser role of target-site insensitivity. These findings highlight the need to explore alternative control tools for this pest and/or explore incorporation of synergists, like piperonylbutoxide as additional chemistries into pesticides formulations to improve their ef-ficacy.

The emergence of drug-resistant tuberculosis forced the development of new drugs and screnning of more effective or less toxic analogs. Mycolic acids biosynthesis is targeted by several antituberculosis drugs toped by the isoniazid being one of the most important in tuberculosis therapy. Recently, perchlozone, acting on another step in FAS-II cycle, received official approval and was included in the Russian national clinical guidelines. Using the serial dilution method on agar 7H10 plates for perchlozone and Sensititre MYCOTB microdilution plate we analyzed the phenotypic properties of primary M. tuberculosis clinical isolates and analyzed the molecular determinants of resistance to isoniazid, ethionamide and perchlozone. We found a wide variation in the MIC of perchlozone from 2 to 64 mg/L, correlating with the overall resistance profile: the MIC was higher for MDR and pre-XDR isolates. The cross-resistance between the ethionamide and the perchlozone was driven by mutations in ethA gene encoding monooxygenase responsible for activation of both drugs. Presumably susceptible to perchlozone wild-type strains had MICs ranged 2–4 mg/L, and the breakpoint estimated to be at 4 or 8 mg/L. In conclusion, susceptibility to perchlozone retained for a part of MDR strains, as does suceptibility to ethionamide, providing the possibility of therapy for such cases based on phenotypic or molecular analysis.

The replacement of chloroquine with artemisinin-based combination therapies (ACTs) for over a decade has had varying impacts on the ability of malaria parasite to sustain its chloroquine resistance prowess in different malaria-endemic regions. We evaluated the frequency of Plasmodium falciparum chloroquine resistance transporter (PfCRT) mutations in an endemic area of southwest Nigeria 17 years after replacement of chloroquine with ACTs for malaria treatment. Genomic DNA was isolated from dried blood spot samples obtained from 129 patients (aged 1-35 years) with microscopically confirmed P. falciparum infection. PfCRT fragments covering codons 72-76, CVMNK (wildtype) and A220 were amplified and sequenced. Two mutant PfCRT haplotypes on residues 72-76 (CVIET and CVINT) were identified with a prevalence of 18.6% and 2.3%, respectively. Interestingly, the CVINT haplotype was identified for the first time in this region. A220S changes were found in 16.3% of samples occurring concurrently with the CVIET haplotype, while a Q271E mutation occurred in a wildtype isolate. The reduced prevalence of the PfCRT mutant alleles in this study may suggest a gradual disappearance of chloroquine-resistant malaria parasites following reduced drug pressure. It may also be an indicator of the ability of malaria parasites to develop resistance gradually against the current first-line regimen.

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

Electrode degradation in continuous resistance spot welding process of BH 220 steel was evaluated by electrode life test, and weldability tests were conducted by geometry features measurement, mechanical property analysis, and electrode diameter measurement with 88 or 176 weld intervals. The analysis of weld geometry shows that the HAZ width, nugget diameter, and nugget area tend to decrease rapidly, while the nugget height tends to firstly increase with the weld repetitions till the welding heat input becomes too small to form the valid nugget. The peak load shows a rapid downward trend, while failure energy and maximum displacement slightly increase till the 176th weld and then decrease. The cavities and pores in the nugget mainly appear after the 176th spot weld. The electrode diameter increases during welding. The reason for the increase in electrode diameter may be that the contact area between the electrode and BH 220 steel sheets becomes smaller in the welding process, which causes the continuous sticking phenomenon between the electrode and the BH 220 steel sheets. In the absence of alloying, the edge of the electrode is geometrically deformed, while Cu-Zn-Fe alloying occurs in the area in contact with the BH 220 steel sheet.

Antibiotic resistance is a pressing global and planetary health challenge. Links between climate change, antibiotic use and the emergence of antibiotic resistance have been well documented, but less attention has been given to the impact(s) of earth systems on specific bacterial livestock diseases at a more granular level. Understanding the precise impacts of climate change on livestock health – and in turn the use of antibiotics to address that ill-health – is important in providing an evidence base to tackle such impacts and to develop practical, implementable and locally acceptable solutions within and beyond current antibiotic stewardship programmes. In this paper, we set out the case for better integration of earth scientists and their specific disciplinary skill set (specifically, problem-solving with incomplete/fragmentary data; the ability to work across four dimensions and at the interface between the present and deep/geological time) into planetary health research. We then discuss a methodology that makes use of risk mapping, a common methodology in earth science but less frequently used in health science, to map disease risk against changing climatic conditions at a granular level. This will enable predictions of future disease risk and risk impacts based on predicted future climate conditions, and thus provide an evidence base for planetary health activists to influence policy and develop mitigations. Our case study – of climate conditions’ impact on livestock health in Karnataka, India – clearly evidences the benefit of integrating earth scientists into planetary health research.

Antimicrobial resistance (AMR) is a global health problem threatening safe, effective healthcare delivery in all countries and settings. The ability of microorganisms to become resistant to the effects of antimicrobials is an inevitable evolutionary process. The misuse and overuse of antimicrobial agents has increased the importance of a global focus on antimicrobial stewardship (AMS). This review provides insight into the current AMS landscape and identifies contemporary actors and initiatives related to AMS projects in eight African countries (Ghana, Kenya, Malawi, Nigeria, Sierra Leone, Tanzania, Uganda, and Zambia), which form a network of countries participating in the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme. We focus on common themes across the eight countries, including the current status of AMR, infection prevention and control, AMR implementation strategies, AMS, antimicrobial surveillance, antimicrobial use, antimicrobial consumption surveillance, a one health approach, digital health, pre-service and in-service AMR & AMS training, access to and supply of medicines, and the impact of COVID-19. Recommendations suitable for adaptation are presented, including the development of a national AMS strategy and incorporation of AMS in pharmacists’ and other healthcare professionals' curricula for pre-service and in-service training.

Mycobacterium tuberculosis is a leading cause of human mortality worldwide and the emergence of drug-resistantstrains, demands the discovery of new classes of antimycobacterials that can be employed in the therapeutic pipeline. Previously, a secondary metabolite Chrysomycin A, isolated from Streptomyces sp. OA161 was shown to have potent bactericidal activity against drug-resistant clinical isolates of M. tuberculosis and different species of mycobacteria. The antibiotic inhibits the mycobacterial topoisomerase I and DNA gyrase leading to bacterial death, but the mechanisms that could cause resistance are currently unknown. To further understand the resistance mechanism, spontaneous resistance mutants were isolated and subjected to whole-genome sequencing. Mutation in a Tet^R family transcriptional regulator MSMEG_1380 was identified in the resistant isolates and was close to an operon encoding membrane protein MSMEG_1381 and MSMEG_1382. Sequence analysis and modeling studies indicated that they are components of the Mmp family of efflux pumps and over-expression of either the operon or individual genes conferred resistance to chrysomycin A, isoniazid, and ethambutol that are in TB therapy. Our study highlights the role of membrane transporter proteins in conferring multiple drug resistance and the utility of recombinant strains overexpressing membrane transporters in the drug screening pipeline.

In the current research work, electrical resistance tomography (ERT) was employed for crystallization process monitoring and visualization. A first-of-its-kind MATLAB-based interactive GUI application “ERT-Vis” is presented. Two case studies involving varied crystallization methods were undertaken. The experiments involving calcium carbonate reactive (precipitative) crystallization for the high conductivity solution-solute media and the cooling crystallization for sucrose crystallization representing the lower conductivity solution-solute combination were designed and performed. The software successfully provided key insights regarding the process progress in both crystallization systems. It could detect and separate the crystal agglomerations in the low as well as high conductivity solutions using visual analytics tools provided. The performance and utility of the software were studied using a software evaluation case study involving domain experts. Participant feedback indicated that ERT-Vis software helps in reconstructing images instantaneously, interactively visualizing, and evaluating the output of the crystallization process monitoring data.

Ovarian cancer is a deadly disease attributed to late-stage detection as well as recurrence and development of chemoresistance. Ovarian cancer stem cells (OCSCs) are hypothesized to be largely responsible for emergence of chemoresistant tumors. Although chemotherapy may initially succeed at decreasing the size and number of tumors, it leaves behind residual malignant OCSCs. In this study, we demonstrate that Aldehyde dehydrogenase 1A1 (ALDH1A1) is essential for the survival of OCSCs. We identified a novel ALDH1A1 inhibitor, compound 974, and used 974 as a tool to decipher the mechanism of stemness regulation by ALDH1A1. Treatment of OCSCs with 974 significantly inhibited ALDH activity, expression of stemness genes, spheroid, and colony formation. In vivo limiting dilution assay demonstrated that 974 significantly inhibited CSC frequency. Transcriptomic sequencing of cells treated with 974 revealed significant downregulation of genes related to stemness and chemoresistance as well as senescence and senescence associated secretory phenotype (SASP). We confirmed that 974 inhibited senescence and stemness induced by platinum-based chemotherapy in functional assays. Overall, these data establish that ALDH1A1 is essential for OCSCs survival and ALDH1A1 inhibition sup-presses chemotherapy induced senescence and stemness. Targeting ALDH1A1 using small molecule inhibitors in combination with chemotherapy therefore presents a promising strategy to pre-vent ovarian cancer recurrence and has potential for clinical translation.

Background: Worldwide, microbes are becoming more dangerous by acquiring virulent skills to adapt and develop antimicrobial resistance (AMR). This is a concern as this increases morbidity, mortality, and costs. Consequently, physicians need to be trained inappropriate prescribing, starting with medical students. Objective: Evaluate medical students' confidence in antimicrobial agent prescribing and drug resistance Methods: Cross-sectional study assessing medical students' knowledge, perception, and confidence in prescribing antimicrobial agents and drug resistance in a Malaysian University. A universal sampling method was used. Results: Most respondents believe that educational input regarding overall prescribing was sufficient. Regarding the principle of appropriate and accurate prescriptions, female medical students had less knowledge [Odds Ratio (OR)=0.51; 95% Confidence Interval (CI) 0.25-0.99; p=0.050]. Year-IV and Year-V students had more excellent knowledge than Year-III students regarding confidence in antibiotic prescribing. Year-V students also showed appreciably higher confidence in the broad principles of prescribing, including infectious diseases, compared to those in other years. Conclusion: Overall, medical students, gain more excellent knowledge and confidence regarding prescribing, including antimicrobials, as their academic careers progress.

Extremely low concentrations of ciprofloxacin may select for antimicrobial resistance. A recent global survey found that ciprofloxacin concentrations exceded safe levels at 64 sites. We assessed if national median ciprofloxacin concentrations in rivers were associated with fluoroquinolone resistance in Escherichia coli. Methods Spearman’s regression was used to assess the country-level association between the national prevalence of fluoroquinolone resistance in E. coli and the median ciprofloxacin concentration in the countries rivers. Results The prevalence of fluoroquinolone resistance in E. coli was positively correlated with the concentration of ciprofloxacin in rivers (ρ=0.36; P=0.011; N=48). Conclusions Steps to reducing the concentrations of fluoroquinolones in rivers may help prevent the emergence of resistance in E. coli and other bacterial species.

Lung cancer (LC) is one of the leading causes of cancer occurrence and mortality worldwide. Treatment of patients with advanced and metastatic LC presents a significant challenge as malignant cells use different mechanisms to resist chemotherapy. Drug resistance (DR) is a complex process that occurs due to a variety of genetic and acquired factors. Identifying the mechanisms underlying DR in LC patients and possible therapeutic alternatives for more efficient therapy is a central goal of LC research. Advances in nanotechnology resulted in the development of targeted and multifunctional nanoscale drug constructs. The possible modulation of the components of nanomedicine, their surface functionalization, and encapsulation of various active therapeutics provide promising tools to bypass crucial biological barriers. These attributes enhance the delivery of multiple therapeutic agents directly to the tumor microenvironment (TME), resulting in reversal of LC resistance to anticancer treatment. This review provides a broad framework for understanding the different molecular mechanisms of DR in lung cancer; presents novel nanomedicine therapeutics aimed to improve the efficacy of treatment of various forms of resistant LC; outlines current challenges in using nanotechnology for reversing DR; and discusses the future directions for clinical application of nanomedicine in management of LC resistance.

Cell monolayers, including endothelial and epithelial cells, play crucial roles in regulating the transport of biomolecules to underlying tissues and structures via intercellular junctions. Moreover, the monolayers form a semipermeable barrier across which leukocyte transmigration is tightly regulated. The inflammatory cytokines can disrupt the epithelial and endothelial permeability, thus the reduced barrier integrity is a hallmark of epithelial and endothelial dysfunction related with numerous pathological conditions, including cancer-related inflammation. Therefore, the assessment of barrier function is critical in in vitro models of barrier-forming tissues. This review summarizes the commercially available in vitro systems used to measure the permeability of cellular monolayers. The presented techniques are separated in two large groups: macromolecular tracer flux assays, and electrical impedance measurement-based permeability assays. The presented techniques are briefly described and compared.

In the present study, the corrosion resistance of amorphous coating and composite coatings in 3.5 wt.% NaCl, 0.5 M H₂SO₄ and 10 wt.% NaOH solution were studied. The composite coatings exhibit superior corrosion resistance. When the content of AT13 （Al₂O₃–13 wt.% TiO₂）was 15 wt.%, the composite coating has the lowest corrosion current density (1.75×10^-6 A cm^-2), which is 5.14×10^-5 A cm^-2 for Fe-based metallic glassy coating, and the highest corrosion potential (-411 mV), which is -580 mV for Fe-based metallic glassy coating. The breakdown potential of the passivation film in 3.5 wt.% NaCl solution was much higher than that of 316L.The long-time immersion corrosion tests carried out on different coatings showed that the corrosion protection effect of coating was enhanced with the increase of the amount of AT13 added.

Background: Obesity and diabetes are two metabolic disorders linked by an inflammatory process named insulin resistance (IR). Various research on the role of gut microbiota in developing obesity and its associated disorders has led to the growing interest in probiotic supplementation. Considering the life-threatening complications of diabesity this mini-review explored the effects of probiotic supplementation on IR in obesity-associated diabetes. Method: This review is based on recent articles from 2005-2020, studying the role of probiotic supplementation on glucose and insulin parameters in healthy and diabetic mouse models. Result: Probiotic supplementation altered the gut microbiota composition, increased short-chain fatty acid production, and decreased pro-inflammatory cytokines. Additionally, they decreased intestinal permeability, circulating lipopolysaccharide, and metabolic endotoxemia hence improved insulin sensitivity and reduced obesity. Although multi-strain probiotic supplementation showed greater benefits than single strain interventions, variations in the concentration of probiotics used and the duration of treatment also influenced the results. Conclusion: Probiotic supplementation could manipulate the gut microbiota by reducing intestinal permeability, inflammation and ameliorate IR and obesity-associated diabetes in animal models which requires further long-term clinical studies in humans.

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

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

Breast cancer (BC) is the most common cancer diagnosed in women worldwide. Approximately 70% of BC patients have the luminal subtype, which expresses hormone receptors (HR+). Adjuvant endocrine treatments are the standard of care for HR+/HER2- BC patients. Over time, approximately 30% of those patients develop endocrine resistance and metastatic disease. Cyclin-dependent kinase inhibitors (CDKi) in combination with an aromatase inhibitor or fulvestrant have demonstrated superior efficacies in increasing progression-free survival, with a safe toxicity profile, in HR+/HER2- metastatic BC patients. CDKi blocks kinases 4/6, preventing G1/S cell cycle transition. However, not all patients respond to CDKi, and those who do respond ultimately develop resistance to the combined therapy. Studies in tumour tissues and cell lines have tried to elucidate the mechanisms underlying this progression, but there are still no conclusive data. Over the last few years, liquid biopsy has contributed relevant information. Circulating tumour materials are potential prognostic markers for determining patient prognosis in metastatic luminal BC, for monitoring disease and for treatment selection. This review outlines the different studies performed using liquid biopsy in patients with HR+ metastatic BC treated with CDKi plus endocrine therapy. We focus mainly on those studies that describe possible resistance mechanisms in circulating tumour-derived material.

Fusarium Head Blight (FHB) is a destructive disease affecting the grain yield and quality of wheat, barley, rye and triticale. Developing varieties with genetic resistance is integral to successfully managing FHB. However, significant knowledge gap exists in the genetic diversity present in triticale for FHB resistance. This information is critical for breeding new varieties of triticale as its production continues to increase. In the present study, a set of 298 winter triticale accessions from a worldwide collection were screened for their type-2 FHB resistance in an artificially inoculated misted nursery with high levels of inoculum density. Most of the triticale accessions were susceptible to FHB, and only 8% of accessions showed resistance in the field nursery screening. The resistant accessions identified in the nursery screening were selected and further screened for three years in greenhouse conditions. Seven accessions were found to show robust FHB resistance over the three years of greenhouse testing. Thirteen accessions showed significantly lower levels of Deoxynivalenol accumulation when compared to the susceptible triticale control. The accessions identified in the study will be useful in triticale and wheat breeding programs for enhancing FHB resistance and reducing DON accumulation.

Irrational use or misuse of antibiotics, particularly by outpatients, increases antibiotic resistance. A lack of public knowledge about ‘Responsible use of antibiotics’ and ‘How to obtain antibiotics’ is a major cause of this. This study aimed to assess the effectiveness of an educational video about antibiotics and antibiotics use to increase outpatient's knowledge in two public hospitals in East Java, Indonesia. A quasi-experimental research setting was used with a one-group pretest-posttest design, carried out from November 2018 to January 2019. The study population consisted of outpatients, to whom antibiotics were prescribed, in two public hospitals in East Java, Indonesia. Participants were selected using a purposive sampling technique; 98 outpatients at MZ General Hospital in S regency and 96 at SG General Hospital in L regency were included. A questionnaire was used to measure the respondents’ knowledge and consisted of five domains, i.e. definition of infections and antibiotics, obtaining the antibiotics, directions of use, storage instructions, antibiotic resistance. The knowledge test score was the total score of the Guttman scale (a dichotomy of ‘yes’ or ‘no’ answers). To determine the significance of the difference in knowledge before and after providing the educational video and in the knowledge score between hospitals, the (paired) Student’s t-test was applied. The educational videos significantly improved outpatients' knowledge, which increased with 41% in MZ General Hospital and 42% in SG General Hospital. An educational video is a useful method to improve the knowledge of the outpatients regarding antibiotics.

The Center for Disease Control and Prevention and the World Health Organization issued a practical approach and Global Action Plan to control the threatening emerging antibacterial resistance. One of the main basis of this plan is the Antimicrobial Stewardship Program (ASPs). This study aimed to evaluate community pharmacists’ awareness and perception towards antimicrobial resistance and ASPs in Jordan. Thus, a qualitative study was conducted through in-depth interviews with twenty community pharmacists. Convienience sampling was used in the study. Qualitative analysis of the data yielded four themes and eleven sub-themes. All the respondents showed good understanding about the causes of antimicrobial resistance. The most important causes reported by them was the non-restricted prescription of antimicrobials. Most of the pharmacists believed that they are competent to provide ASPs, however, they believed that there are several barriers against the implementation of ASPs in community pharmacies in Jordan. Barriers demonstrated by the pharmacists, including organizational obstacles, resources obstacles, and personal obstacles. As a conclusion, this study revealed several barriers against the implementation of ASPs in community pharmacies in Jordan. Incorporating ASPs in the community pharmacy settings requires proper pharmacist training, several academic disciplines team efforts, and good pharmacy practice of antimicrobial guidelines.

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeted resistance to β-lactams including carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones.

Among various metal-based nanoparticles, silver nanoparticles (AgNPs) manifest superior inhibitory effect against several microorganisms. In fact, the AgNPs based therapy has been reported to inhibit both sensitive as well resistant isolates of bacteria and other disease causing microbes with equal propensity. Keeping this fact into consideration, we executed bio-mediated synthesis of AgNPs employing Hibiscus rosa sinensis flower extract. The as-synthesized AgNPs were evaluated for their potential to inhibit Streptococcus mutans (S. mutans), one of the main causative bacteria for dental caries. Beside several other reasons, orthodontic appliances have also been reported to facilitate infliction of oral cavity with a range of microbes including S. mutans. To determine the growth inhibitory and anti-adherence activity of AgNPs on orthodontic appliance, we performed microbiological assays employing AgNPs adsorbed on to the orthodontic wires. Topographic analysis of orthodontic wires was executed by scanning electron microscopy. In addition to antimicrobial and antibiofilm activity against oral S. mutans, the as-fabricated AgNPs demonstrated significant inhibitory and anti-biofilm properties against other biofilm forming bacteria such as Escherichia coli and Listeria monocytogenes as well.

Certain studies have reported various insulin resistance responses to ambient heavy metal pollution, but few have reported such responses to occupational heavy metal pollution. Even fewer have demonstrated a relationship between mixture effects of heavy metals and insulin resistance in welding workers. Overall, we recruited 53 welders and 48 administrative staff from a shipyard located in northern Taiwan. Personal exposure to heavy metals was monitored for PM2.5 and urine. Blood samples from each participant were collected from the antecubital vein after fasting. Urine samples from each participant were collected in the same period as blood samples. The geometric mean levels for chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), and cadmium (Cd) in the PM2.5 of the personal breathing zone and urinary Mn of welders were significantly higher than those in administrative staffs. Ambient Cr, Co, Ni, and Cu levels in the PM2.5 and urinary Cd were positively related to HOMA2-IR after adjusting for personal covariates (PM2.5-Cr: β=0.036, 95%C.I.: 0.002 to 0.070; PM2.5-Co: β=0.040, 95%C.I.: 0.002 to 0.077; PM2.5-Ni: β=0.054, 95%C.I.: 0.013 to 0.094; PM2.5-Cu: β=0.049, 95%C.I.: 0.010 to 0.088; U-Cd: β=0.209, 95%C.I.: 0.052 to 0.366, respectively). Our findings indicated the PM2.5 metal components and urinary metals were associated with increased insulin resistance in shipyard welders.

Cucumber green mottle mosaic virus (CGMMV) is a re-emerging threat to greenhouse cucumber and other Cucurbitaceae crop productions worldwide. This seed-borne virus can easily spread from a contaminated seed to seedlings and to adjacent plants through mechanical contact of the foliage of diseased and healthy plants causing extensive yield losses. Additionally, infection may not be limited to the current crop but may also affect subsequent crops due to the long-term persistence of the virus on contaminated crop residues, greenhouse hard surfaces and soil or soil-less greenhouse substrates. In the present work, three greenhouse trials were conducted to develop an integrated pest management strategy towards controlling CGMMV in commercial cucumber greenhouses, by implementing an effective sanitization program and using resistant and grafted cucumber varieties. Results of sanitization trial highlighted that pressure washing and cleansing with an alkaline foam cleanser has eliminated CGMMV on some of the most heavily infested areas. However, three successive applications of cleanser and disinfectants were essential to completely eliminate CGMMV on porous and uneven surfaces, such as cement alleyway, tray gutter and floor mats. The varietal trial revealed that out of 15 cucumber varieties evaluated, two Mini (‘Katrina’ and ‘Khassib’) and three Long English (‘Sepire’, ‘Bomber’ and ‘LC13900’) had reduced or delayed CGMMV infection spread in the greenhouse but were intermediate in yield. The varieties ‘Sunniwell’ and ‘Bonbon’ were the most tolerant to CGMMV. They showed a high CGMMV infection level without compromising yield. These results proved the need for new productive cucumber varieties with CGMMV resistance. Grafting experiment showed only yield increase in case of grafted ‘Picowell’ over ‘Bonbon’ and not marked CGMMV resistance, which is a much desirable result when the grafting experiments are evaluated for their economic potential. In all, the current experimental trials unfold unique methodologies on CGMMV management in commercial greenhouses that are recommended to the growers to be followed for reducing crop losses and get benefitted on revenue compromise.

Usage of antimicrobials in veterinary practices has always been under scrutiny due to the perceived risk of resulting in antimicrobial-resistant pathogens. This creates the necessity for understanding the role of the prescriber group. Hence, we conducted a cross-sectional survey among veterinary practitioners from August to November 2019 in the Chattogram district of Bangladesh, aiming to assess the practitioner’s perceptions regarding antimicrobial prescribing and antimicrobial resistance (AMR) issue. We collected responses from 100 veterinarians engaged in the treatment of the large animal, poultry, and pet animal through a self-administrated questionnaire. Proportions were calculated for categorical variables and the results are presented using visual aids. Our study revealed two key barriers - scarcity of enough information on antimicrobial used, and the lack of training in the proper prescription of antimicrobials. Participants recognized that prescribing too many varieties of antimicrobials and the use of an incomplete course of drugs as two very important causes for the development of antimicrobial resistance. In addition, prescription of inappropriate doses and incentives from pharmaceutical companies were dubbed as important causes. We also found that along with clinical features and types of organisms, the availability of drugs in the local market and the economic conditions of farmers have potential impacts on the antimicrobials prescribing decision of the veterinarians. However, all participants recognized the emerging threats of AMR. Results suggested that capacity building of veterinarians and the maintenance of strong coordination are crucial in ensuring the proper engagement of veterinarians as the front-line fighters for tackling the AMR issue.

The light response and resistance switching behavior in BaTiO3 (BTO) films are studied for a symmetric Pt/BTO/Pt structure. The resistance of films as a function of time with and without ultraviolet light has been studied. Furthermore, resistance switching behavior was clearly observed based on the application of 365 nm wavelength ultraviolet light. Consequently, the polarities of resistance switching can be controlled by ultraviolet light when the energy is larger than the band excitation energy. It is proposed that the polarity of the resistance switching is dictated by the competition of the ferroelectricity and oxygen vacancy migration. This provides a new mechanism for modulating the state of ferroelectric resistive memory devices.

Forty-eight Pasteurella multocida isolates were recovered from porcine pneumonic lungs collected in Norwestern Spain (2017- 2019). These isolates were characterized for their minimal inhibition concentrations to twelve antimicrobial agents and for the appearance of eight resistance genes: tetA, tetB, blaROB1, blaTEM, ermA, ermC, mphE and msrE. Relevant resistance percentages were shown to teracyclines, sulphamethoxazole/trimethoprim and tiamulin, thus suggesting that P. multocida isolates were mostly susceptible to amoxicillin, ceftiofur, enrofloxacin, florfenicol, marbofloxacin and macrolides. 29.2% of isolates were resistant to more than two antimicrobials. The tetracycline resistance genes (tetA and tetB) were detected in 22.9% of the isolates, but none was positive to both simultaneously; blaROB1 and blaTEM genes were found in one third of isolates but both genes were detected simultaneously in only one isolate. ermC gene was observed in 41.7% of isolates, a percentage that decreased until 22.9% for msrE; finally, ermA was harboured by 16.7% and mphE was not found in any of them. Six clusters were established based on hierarchical clustering analysis on antimicrobial susceptibility for the twelve antimicrobials. Generally, it was unable to foresee the antimicrobial susceptibility pattern for each family and the association of each particular isolate inside the clusters established from the presence or absence of the resistance genes analyzed.

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.

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.

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.

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.

A fully automated bacteria whole genome sequencing (WGS) assay was evaluated to characterize Mycobacterium tuberculosis (MTB) and non-tuberculosis Mycobacterium (NTM) clinical isolates. Results generated were highly reproducible with 100% concordance in species and sub-lineage classification, and 92% concordance between antimicrobial resistance (AMR) genotypic and phenotypic profiles. These findings demonstrate that a fully automated WGS assay, with a short turnaround time of 24.5 hours, provides timely and valuable insights into MTB outbreak investigation while providing reliable genotypic AMR profiling consistent with traditional antimicrobial susceptibility tests (AST). This study establishes a favorable proposition in the adoption of an end-to-end fully automated WGS solutions for decentralized TB diagnostics, thereby aiding in WHO’s vision of tuberculosis eradication.

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.

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

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.

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.