In MBSE there is yet no converged terminology. The term ’system model’ is used in different contexts in literature. In this study we elaborated the definitions and usages of the term ’system model’, to find a common definition. 104 publications have been analyzed in depth for their usage and definition as well as their meta-data e.g., the publication year and publication background to find some common patterns. While the term is gaining more interest in recent years it is used in a broad range of contexts for both analytical and synthetic use cases. Based on this three categories of system models have been defined and integrated into a more precise definition.

This article discusses the use of game design as a method for interdisciplinary project-based teaching in secondary school education to convey informatics and society topics. There is a lot of knowledge about learning games but little background on project-based teaching using game design as a method. We present the results of an analysis of student-created games and an evaluation of a student-authored database on learning contents found in commercial off-the-shelf games. We further contextualise these findings using a group discussion with teachers. Results underline the effectiveness of project-based teaching to raise awareness for informatics and society topics. We further outline informatics and society topics that are particularly interesting to students, genre preferences and potentially engaging game mechanics stemming from our analyses.

The ubiquity of mobile sensors (such as GPS, accelerometer and gyroscope) together with increasing computational power have enabled an easier access to contextual information, which proved its value in next generation of the recommender applications. The importance of contextual information has been recognized by researchers in many disciplines, such as ubiquitous and mobile computing, to filter the query results and provide recommendations based on different user status. A context-aware recommendation system (CoARS) provides a personalized service to each individual user, driven by his or her particular needs and interests at any location and anytime. Therefore, a contextual recommendation system changes in real time as a user’s circumstances changes. CoARS is one of the major applications that has been refined over the years due to the evolving geospatial techniques and big data management practices. In this paper, a CoARS is designed and implemented to combine the context information from smartphones’ sensors and user preferences to improve efficiency and usability of the recommendation. The proposed approach combines user’s context information (such as location, time, and transportation mode), personalized preferences (using individuals past behavior), and item-based recommendations (such as item’s ranking and type) to personally filter the item list. The context-aware methodology is based on preprocessing and filtering of raw data, context extraction and context reasoning. This study examined the application of such a system in recommending a suitable restaurant using both web-based and android platforms. The implemented system uses CoARS techniques to provide beneficial and accurate recommendations to the users. The capabilities of the system is evaluated successfully with recommendation experiment and usability test.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori (H. pylori) infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To meet the need to develop test systems for personalized drug selection, we conducted a study of H. pylori molecular resistance in Moscow using a self-developed Sanger sequencing test platform. We validated our test system on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100%, and to levofloxacin - 93% and 92%, respectively. Then we tested our platform on 112 H. pylori -positive patients who had not previously received proton pump inhibitors (PPI) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples, and to levofloxacin in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G, to levofloxacin resistance – 261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.

Hospital-based programs democratize mRNA therapeutics by facilitating the processes to translate a novel RNA idea from the bench to the clinic. Because mRNA is essentially biological software, therapeutic RNA constructs can be rapidly developed. The generation of small batches of clinical grade mRNA to support IND applications and first-in-man clinical trials, as well as personalized mRNA therapeutics delivered at the point-of-care, is feasible at a modest scale of cGMP manufacturing. Advances in mRNA manufacturing science and innovations in mRNA biology, are increasing the scope of mRNA clinical applications.

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

Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19 in several countries. By acting as a substrate for RdRp, favipiravir gets incorporated into the nascent viral RNA and prevents strand extension. A high mutation rate of SARS-CoV-2 RdRp may facilitate antigenic drift as an answer to the host immune response, thereby generating resistance of virus to favipiravir. Therefore, it is extremely crucial to predict potential mutational sites in the RdRp and the emergence of structural modifications contributing to drug resistance. Here, we used high-throughput interface-based protein design to generate >100,000 designs and identify mutation hotspot residues in the favipiravir-binding site of RdRp. Several mutants had lower binding affinities to favipiravir, out of which hotspot residues with a high propensity to undergo positive selection were identified. The results showed that the designs retained an average of 97 to 98% sequence identity, suggesting that SARS-CoV-2 can develop favipiravir resistance with just a few mutations. Notably, we observed that out of 134 mutations predicted designs, 63 specific mutations were already present in the CoV-GLUE database, thus attaining ~47% correlation match with the clinical sequencing data. The findings improve our understanding of the potential signatures of adaptation in SARS-CoV-2 against favipiravir and management of COVID-19. Furthermore, they can help develop exhaustive strategies for robust antiviral design and discovery.

Carbapenem resistant Enterobacteriaceae (CRE) has been public health risk in several countries and recent reports indicate the emergence of CRE in food animals. This study was conducted to investigate the occurrence, resistance patterns, and phylogenetic diversity of CRE E.coli from chicken. Routine bacteriology, PCR detection of E.coli species, multiplex PCR to detect carbapenemase encoding genes and phylogeny of CRE E. coli were conducted. The results show that 24.36 % (19/78) were identified as CRE based on the phenotypic identifications of which 17 were positive for the tested carabanemase genes. The majority, 57.99% (11/19) of the isolates harbored multiple carbapenemase genes. Four isolates harbored all blaNDM blaOXA, blaIMP, five and two different isolates harbored blaNDM and blaOXA, and blaOXA and blaIMP respectively. The Meropenem, Imipenem and Ertapenem MIC values for the isolates ranged from 2g/mL to ≥256g/mL. Phylogenetic grouping showed that the CRE E.coli isolates belonged to five different groups; groups A, B1, C, D and unknown. The detection of carbapenem resistant E.coli in this study shows that CRE is has become an emerging problem in farm animals, particularly, in poultry farms. This also implies the potential public health risks posed by CRE from chicken to the consumers.

Drug discovery utilizes high-throughput screening (HTS) methods applying target and cell-based assays. This review discusses the challenges and benefits associated with these assays in HTS. Discussed the strategies that can be applied for the development of screening assays through primary and secondary screens for target identification. Further discussion on identify-ing the most efficacious drugs following these approaches in cancer. Even though various drugs have been identified to treat cancer, there is high demand of more relevant phenotypic assays to produce desired diseased phenotype to only highlighting the specific targets instead of off-targets. Hopefully, the new developing strategies could provide innovative drugs to treat cancer patients to reduce mortality rate.

The correlations of seismic noise, recorded during 1997-2022 at 229 stations around the world are investigated. The property of waveforms, known as the Donoho-Johnston threshold, is analyzed, which separates the absolute values of the orthogonal wavelet coefficients into "small" and "large". Network of 50 reference points is considered. For each reference point, a time series with a time step of 1 day is calculated as the median of the values of the DJ index from the 5 nearest stations. For each reference point, the correlations between the values of the DJ index at other reference points are calculated in a sliding time window of 365 days. Average values of the DJ index decrease, which is interpreted as indicators of global seismic hazard increasing. The maximum distances between reference points with strong correlations show an explosive increase after 2011. Bursts in the mean coherences between the length of day (LOD) and the values of the DJ index at the reference points precede the release of seismic energy with a delay of about 530 days. High amplitude of the DJ index response to LOD for the times 2020-2022 was identified, which may forecast a strong earthquake in the second half of 2023.

Noise in requirements has been known to be a defect in software requirements specifications (SRS). Detecting defects at an early stage is crucial in the process of software development. Noise can be in the form of irrelevant requirements that are included within a SRS. A previous study had attempted to detect noise in SRS, in which noise was considered as an outlier. However, the resulting method only demonstrated a moderate reliability due to the overshadowing of unique actor words by unique action words in the topic-word distribution. In this study, we propose a framework to identify irrelevant requirements based on the MultiPhiLDA method. The proposed framework distinguishes the topic-word distribution of actor words and action words as two separate topic-word distributions with two multinomial probability functions. Weights are used to maintain a proportional contribution of actor and action words. We also explore the use of two outlier detection methods, namely Percentile-based Outlier Detection (PBOD) and Angle-based Outlier Detection (ABOD), to distinguish irrelevant requirements from relevant requirements. The experimental results show that the proposed framework was able to exhibit better performance than previous methods. Furthermore, the use of the combination of ABOD as the outlier detection method and topic coherence as the estimation approach to determine the optimal number of topics and iterations in the proposed framework outperformed the other combinations and obtained sensitivity, specificity, F1-score, and G-mean values of 0.59, 0.65, 0.62, and 0.62, respectively.

Animal-based measures are the measure of choice in animal welfare assessment protocols as they can often be applied completely independently to the housing or production system employed. Although there has been a small body of work on potential animal-based measures for farmed crocodilians [1-3], they have not been studied in the context of an animal welfare assessment protocol. Potential animal-based measures, that could be used to reflect the welfare state of farmed crocodilians, were identified and aligned with the Welfare Quality® principles of good housing, good health, good feeding and appropriate behaviour. A consultation process with a panel of experts was used to evaluate and score the potential measures in terms of validity and feasibility. This resulted in a toolbox of measures being identified for further development and integration into animal welfare assessment on the farm. Animal-based measures related to ‘good feeding’ and ‘good health’ received the highest scores for validity and feasibility by the experts. There was less agreement on the animal-based measures that could be used to reflect ‘appropriate behaviour’. Where no animal-based measures were deemed to reliably reflect a welfare criterion nor be useful as a measure on the farm, additional measures of resources or management were suggested as alternatives. Future work in this area should focus on the reliability of the proposed measures and involve further evaluation of their validity and feasibility as they relate to different species of crocodilian and farming system.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

Given the increase in consumers’ preferences for coffee, it is becoming important to understand their decision-making processes in the coffee chain context. To deepen the understanding of sustainable outcomes in this context, this study investigates the role of dedication- and constraint-based mechanisms in forming consumers’ repurchase and positive word-of-mouth (WOM) intentions, two critical sustainable outcomes. We examined the effects of coffee quality, the quality of the physical environment, and service quality in accelerating the formation of dedication-based factors. Moreover, this study offers an in-depth understanding of the enablers of perceived switching costs. Data collected from 238 university students that frequently visit coffee chains are empirically tested against the proposed theoretical framework by using structural equation modeling. The results confirm that both dedication- and constraint-based factors substantially predict consumers’ sustainable outcomes in the coffee chain context. Brand image and perceived switching costs play an important role in enhancing consumers’ repurchase and positive WOM intentions compared with customer satisfaction. Coffee quality is significantly associated with both customer satisfaction and brand image, whereas the quality of the physical environment and service quality are only significantly associated with brand image. Habit is found to be the key enabler of perceived switching costs, while loyalty programs have no significant impact on perceived switching costs.

Effectively mapping and monitoring rubber plantation is still changing. Previous studies have explored the potential of phenology features for rubber plantation mapping through a pixel-based approach (pixel-based phenology approach). However, in fragmented mountainous Xishuangbanna, it could lead to noises and low accuracy of resultant maps. In this study, we investigated the capability of an integrated approach by combining phenology information with an object-based approach (object-based phenology approach) to map rubber plantations in Xishuangbanna. Moderate Resolution Imaging Spectroradiometer (MODIS) data were firstly used to acquire the temporal profile and phenological features of rubber plantations and natural forests, which delineates the time windows of defoliation and foliation phases. Landsat images were then used to extract a phenology algorithm comparing three different approaches: pixel-based phenology, object-based phenology, and extended object-based phenology to separate rubber plantations and natural forests. The results showed that the two object-based approaches achieved higher accuracy than the pixel-based approach, having overall accuracies of 96.4%, 97.4%, and 95.5%, respectively. This study proved the reliability of a phenology-based rubber mapping in fragmented landscapes with a distinct dry/cool season using Landsat images. This study indicated that the object-based phenology approaches can effectively improve the accuracy of the resultant maps in fragmented landscapes.

Rice blast, caused by Magnaporthe oryzae, poses significant threat to rice production. Rice blast susceptibility has been observed in Japanese rice varieties with excellent eating quality. Enhancing blast resistance is essential to ensure minimal use of agricultural chemicals. Two types of blast resistance are observed: true resistance, which is a type of qualitative resistance expressed by a major gene, and field resistance, which is a type of quantitative resistance expressed by multiple micro-acting genes. ‘Resistance collapse’, in which a variety with a true resistance gene becomes diseased by blast fungus races compatible with the resistance gene, has been observed. Varieties carrying blast-resistance genes, such as Pb1 (panicle blast resistance 1), have been developed through DNA marker-assisted selection. In this review, we focus on the Pb1, which expresses strong quantitative resistance to panicle blast and has been widely used in Japan without showing ‘resistance collapse’ for 40 years. Pb1 is an ‘adult plant resistance gene’ that does not exert strong selection pressure on the blast population during the leaf blast stage, thus preventing the selective multiplication of Pb1-compatible blast strains. This epidemiological mechanism prevents ‘resistance collapse’. Interdisciplinary research and breeding are required to sustainably use genes that induce high field resistance.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

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

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite the latest advances, a major clinical issue in EOC is the disappointing prognosis related to chemoresistance in almost one-third of cases. Drug resistance relies on heterogeneous cancer stem cells (CSCs), endowed with tumor-initiating potential, leading to relapse. No biomarkers of chemoresistance have been validated yet. Recently, major signaling pathways, micro ribonucleic acids (miRNAs), and circulating tumor cells (CTCs) have been advocated as putative biomarkers and potential therapeutic targets for drug resistance. However, further investigation is mandatory before their routine implementation. In accordance with the increasing rate of therapeutic efforts in EOC, the need for biomarker-driven personalized therapies is growing. This review aims to discuss the emerging hallmarks of drug resistance with an in-depth insight into the underlying molecular mechanisms lacking so far. Finally, a glimpse of novel therapeutic avenues and future challenges will be provided.

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

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Drug repurposing, rebranding an existing drug for a new therapeutic indication, is deemed a beneficial approach for a quick and cost-effective drug discovery process by skipping preclinical, Phase 1 trials and pharmacokinetic studies. Several psychotropic drugs including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antide-pressants (TCAs) were studied for their potential application in different diseases es-pecially in cancer therapy. Fluoxetine (FLX) is one of the most prescribed psychotropic agents from SSRIs class for the treatment of several neuropsychiatric disorders with a favourable safety profile. FLX exhibited different oncolytic effects via mechanisms dis-tinct from its main serotonergic activity. Taking advantage of its ability to rapidly pen-etrate the blood-brain barrier, FLX could be particularly useful in brain tumors. This was proved by different in vitro and in vivo experiments using FLX as a monotherapy or combination with temozolomide (TMZ) or radiotherapy. In this review of literature, we summarize the potential pleiotropic oncolytic roles of FLX against different cancers highlighting the multifaceted activities of FLX and its ability to interrupt cancer prolif-eration via several molecular mechanisms and even surmount multidrug resistance (MDR). We elaborated on the successful synergistic combinations such as FXR/temozolomide and FXR/raloxifene for the treatment of glioblastoma and breast cancer, respectively. We showcased beneficial pharmaceutical trials to load FLX on car-riers to enhance its safety and efficacy on cancer cells. This is the first review article ex-tensively summarizing all previous FLX repurposing studies for the management of cancer.

In this study, we aimed to determine the trend of antimicrobial resistance pattern of pathogens isolated in samples collected from patients hospitalized in the intensive care unit (ICU), in selected periods before and after COVID-19. A retrospective study of bacterial pathogens was performed on 1267 patients. The resistance patterns were analyzed using Vitek 2 Compact system. Positive-bacterial culture data of 1695 samples from pre-COVID-19 period and 1562 from post-COVID-19 period were obtained. The most frequently isolated in both periods were Staphylococcus aureus and Klebsiella spp. Klebsiella spp. had a statistically significant increase in resistance rates in the post COVID-19 period, against colistin, gentamicin and aztreonam. For E. coli strains, it was registered a significant increase against colistin and a significant decrease against levofloxacin and imipenem. For Acinetobacter spp. strains it was observed a significant increase against colistin. More than 50% from the Staphylococcus aureus strains were MRSA with statistically significant increases in antimicrobial resistance rate in the post-COVID-19 period against doxycycline, linezolid, rifampicin and teicoplanin. The study revealed a significantly increasing trend of the antimicrobial resistance rate of Gram-negative pathogens (Klebsiella spp., Acinetobacter spp.) against certain antibiotics, including those used only in cases where there are no other therapeutic options.

Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is one of the most destructive diseases in banana farming worldwide. Knowledge of the factors of genetic diversity and virulence of the pathogen contributes to the development of resistant cultivars and in management strategies based on exclusion. In this study, phenotypic traits such as virulence and aggressiveness in a sample of 52 Foc isolates, were analyzed and their relationship to the presence of putative effectors of gene SIX (Secreted in Xylem) pathogenicity homologues, verified. According to the dissimilarity matrix, there were three isolates closest to the standard Foc race 1 strain. Isolates 229A and 218A, were selected according to their aggressiveness profile in 'Grand Naine' and 'Prata-Anã', respectively, I order to replace the standard isolate of race 1 in the resistance screening process carried out by the breeding program. Two homologues of the SIX8 gene, SIX8a and SIX8b, are present in isolates of Foc from Brazil and the SIX8b gene correlates with avirulence in the cultivar ‘Grand Naine’ (Cavendish). These results are important to support the banana genetic breeding program by identification of sources of resistance to Foc and contribute in the establishment of the function of SIX effector proteins.

Antibiotic resistance currently considered as a global concern mostly impacting low- and middle-income nations and it can be accelerated by antibiotic abuse and other forms of excessive antibiotic use. There is little data on community practices and understanding in Somaliland on antibiotics and antibiotic resistance. To provide evidence-based communication intervention techniques for safer antibiotic use the qualitative study was done from November 1st to December 1st, 2023, and consisted of in-depth semi-structured interviews with adult heads of households in Hargeisa, Somaliland, using purposive and snowball sampling strategies. Participants were chosen from a variety of medical and educational backgrounds. Thematic analysis was used to investigate community knowledge and antibiotic use in the sampled population. To investigate the level of awareness on antibiotic use, 20 respondents (households) were questioned (Table 1). Of these, 17 (85%) became aware of the term antibiotic itself, with 7 (35%) being prescribed by a physician, 9 (45%) receiving laboratory diagnosis when using antibiotics, and 6 (30%) becoming aware of the potential risks associated with improper antibiotic use. This study highlighted the community's lack of understanding about antibiotic use. The majority of the study participants knew the phrase "antibiotic" but had no idea what it meant, the side effect of the antibiotics and other medical science related information regarding how to safely use antibiotics. According to the findings, initiatives for antibiotic stewardship should focus on community education to prevent antibiotic misuse or abuse.

Seawater has been proposed as a reservoir for antibiotic resistant bacteria and antibiotic resistance genes, thus representing a risk to public health. In this study, we evaluated the presence of antibiotic resistance determinants (bacteria and genes) in 77 seawater samples collected at different points along the coast of the Gulf of Valencia (Spain). Specifically, indicators of fecal contamination bacteria, Escherichia coli and Enterococcus sp. were isolated, and their antibiotic resistance profiles were analyzed by using the Sensititre® system, followed by the detection of main antibiotic resistance genes (blaTEM, qnrS, tetW, sulI, and ermB). The highest frequencies of resistance in E. coli isolates were detected against ampicillin (35.1%) and ciprofloxacin (17.5%), followed by sulfamethoxazole and trimethoprim (15.7%), while 23% of enterococci isolates showed resistance to a single antibiotic, 20% against tetracycline and 3% against daptomycin. By PCR, 93% of the E. coli strains showed the blaTEM and sulI resistance genes. Among the enterococci, the presence of the blaTEM gene was detected in 40% of the isolates, while the rest of the genes were present at very low rates. Among the water samples, 57% were positive for at least one of the tested genes, being blaTEM gene the most commonly found (47%), followed by qnrS (33%) and sulI (23%) genes. These results show that seawater, in addition to having a high rate of fecal contamination, can contribute to the spread of antibiotic resistance.

Antimicrobial resistance is one of the most important global health issues identified in recent decades. Different approaches have been used to establish the presence and abundance of antimicrobial resistance genes (ARGs) in the environment. In this study, we analyzed soil samples from Fildes Peninsula (King George Island, maritime Antarctica), exposed to different types of impact. The objective of the work was to identify ARGs in the samples, and evaluate if these genes were located in plasmids, using two different strategies. A metagenomic analysis was used to identify ARGs and if they were associated to plasmid sequences. The analysis showed that the site highly exposed to anthropogenic activity had a higher number of ARGs compared to other sites. A high percentage of those ARGs (19.4%), were located in plasmidic contigs. We also assessed replicon mobilization, using microbial communities from these soil samples as donors through an exogenous plasmid isolation method. In this case, we could recover plasmids with ARGs in a Tcr transconjugant clone. Although they could not be fully assembled, we could detect broad host range IncP1 and IncQ plasmid sequences. Our results indicate that sewage impacted soils could be a hotspot for ARGs spread into the Antarctic environment

Periodic assessment of bacterial contamination is necessary as it allows proper guidance in cases of eye infections through the use of appropriate antibiotics. Due to the extensive use of antibiotic treatment, most of the contamination flora is resistant to the usual ophthalmic antibiotics. The present study shows an updated picture of the susceptibility of Gram-positive and Gram-negative bacteria found on the ocular surface to the most commonly used antibiotic agents in patients undergoing cataract surgery. A total of 993 patients were included in the study with ages between 44 and 98 years old. Conjunctival culture was collected 7 days before cataract surgery. The response of Gram-positive and Gram-negative bacteria to various antibiotic classes like glycopeptides, cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, phenicols, tetracyclines, rifamycins, macrolides and penicillins was assessed. From the tested antibiotics, vancomycin had 97.8% efficacy on Gram-positive bacteria. In the cephalosporin category, we observed an increased resistance of the cefuroxime for both Gram-positive and negative bacteria. Antibiotics that have more than 90% efficacy on Gram-positive bacteria are: meropenem, imipenem, netilmicin, amikacin and rifampicin. On Gram-negative bacteria, we found 100% efficacy of all tested fluoroquinolones, aminoglycosides (except for tobramycin), doxycycline, azithromycin, clarithromycin and chloramphenicol. The current study illustrates patterns of increased resistance of certain bacteria present on ocular surface to some of the commonly used antibiotics in ophthalmological clinical practice. One such revealing example is cefuroxime, which has been highly used as an intracameral antibiotic for the prevention of bacterial endophthalmitis after cataract surgery.

Maize (Zea mays L.) stands as one of the most extensively cultivated crops globally, offering significant contributions to food, animal feed, and biofuel production. Maize yield is significantly impacted by diverse climate and soil variables, yet its productivity faces hindrances due to abiotic stresses, including drought, salinity, extreme temperatures, and cold conditions. In confronting these hurdles, the field of crop breeding has undergone a transformation thanks to high-throughput sequencing technologies (HSTs). These advancements have streamlined the identification of beneficial quantitative trait loci (QTL), associations between markers and traits (MTAs), as well as genes and alleles that contribute to crop improvement. Presently, well-established omics techniques such as genomics, transcriptomics, proteomics, and metabolomics are being amalgamated into maize breeding studies. These approaches have unveiled new biological markers that are being employed to bolster maize's capacity to withstand an array of challenges. In this chapter, we explore the current knowledge regarding the morpho-physiological and molecular mechanisms that underlie the resistance and tolerance of maize to biotic and abiotic stresses. The focus is on utilizing omics techniques to augment maize's ability to withstand these challenges. Moreover, it emphasizes the significant potential of integrating various omics techniques to tackle the challenges presented by biotic and abiotic stress in maize productivity, contrasting with singular approaches.

Inspired by the process of bone formation in living organisms, many studies have been conducted to develop organic-inorganic composite materials by generating calcium phosphate crystals within solutions or dispersions of polymers with appropriate functional groups. Bones are composite materials consisting of organic polymers (mainly Type I collagen), carbonated apatite, and water, with volume fractions 35-45%, 35-45%, 15-25%, respectively. Carbonated apatite in bone contributes to rigidity, while organic polymers and water contribute to toughness. The inorganic crystal, carbonated apatite, is a plate-shaped crystal with dimensions of 50 nm × 25 nm × 1-4 nm, generating a significant organic-inorganic interface due to its nanoscale size. This interface is believed to absorb externally applied forces to dissipate mechanical energy to thermal energy. Creating such nanometer-scale structures using top-down approaches is challenging, making bottom-up methods like co-precipitation of polymer and inorganic crystals more suitable. In this account, efforts to develop eco-friendly mechanical materials using biomass such as cellulose and starch based on the bottom-up approach to bone-like composites are described.

Alopecurus myosuroides (blackgrass) is a problematic weed of Western European winter wheat and its success is largely due to widespread multiple-herbicide resistance. Previous analysis of F2 seed families derived from two distinct blackgrass populations exhibiting equivalent non-target site resistance (NTSR) phenotypes shows resistance is polygenic and evolves from standing genetic variation. Using a CIDER-seq pipeline we show that herbicide resistant (HR) and herbicide sensitive (HS) F3 plants from these F2 seed families as well as the parent populations they were derived from carry extra-chromosomal circular DNA (eccDNA). We identify the similarities and differences in the coding structures within and between resistant and sensitive populations. Although the numbers and size of detected eccDNAs varied between the populations, comparisons between HR and HS blackgrass populations identified shared and unique coding content, predicted genes, and functional protein domains. These include genes related to herbicide detoxification such as Cytochrome P450s, ATP-binding cassette transporters and glutathione transferases including AmGSTF1. eccDNA content was mapped to the Alopecurus myosuroides reference genome, revealing genomic regions at distal end of chromosome 5 and the near center of chromosome 1 and 7 as regions with high number of mapped eccDNA gene density. Mapping to 15 known herbicide-resistant QTL regions showed the eccDNA coding sequences match 12 with four QLT matching HS coding sequences one region only contained HR coding sequences. These findings establish that like other pernicious weeds, blackgrass has eccDNAs that contain homologs of chromosomal genes, and these may contribute genetic heterogeneity and evolutionary innovation to rapidly adapt to abiotic stresses including herbicide treatment.

Pulmonary infections with Mycobacterium avium occur in susceptible individuals following exposure to the bacterium in the environment, where it often persists in biofilms. Many methods have been used to generate biofilms of M. avium, and it is unknown whether different approaches generate similar structures and cell phenotypes. To make a parallel comparison of in vitro biofilm ultrastructure, extracellular matrix (ECM) composition, and drug susceptibility of biofilm resident bacteria, we used two published methods to generate M. avium biofilms: four week incubation in M63 medium or 24 hour exposure to dithiothreitol (DTT). Scanning electron microscopy revealed differences in biofilm ultrastructure between the two methods, including variation in appearance of ECM materials and morphology of resident cells, while light microscopy and staining with calcofluor white indicated that both biofilms contained polysaccharides characteristic of cellulose. Measuring susceptibility of biofilms to degradation by enzymes suggested differences in structurally important ECM molecules, with DTT biofilms having important protein and, to a lesser extent, cellulose components, and M63 biofilms having moderate protein, cellulose, and DNA components. Both biofilms conferred resistance to the bactericidal effects of amikacin and clarithromycin, with resident cells being killed at &gt;10-fold lower rates than planktonic cells at almost all concentrations. Though these comparisons indicate differences in biofilm responses by M. avium under differing conditions, they also suggest common features of biofilm formation including cellulose production and antimicrobial resistance.

Background: Understanding the physicians’ knowledge, attitudes and antimicrobial prescribing behaviour is a crucial step towards designing strategies for optimal use of these agents. Methods: A cross-sectional online survey was conducted among clinicians across India between “May to July 2022” using a self-administered questionnaire in English comprising of 35 questions pertaining to demographic characteristics, knowledge, attitude and practices domains. Results. A total of 544 responses were received from 710 physicians contacted. 60 percent participants were males with mean age of 34.7 years. Mean ± SD scores for knowledge, attitude and practices domains were 8±1.6, 20.2±3.5 and 15.3±2.1, respectively. Higher scores were associated with basic [odds ratio (95% C.I.), P value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03] and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe classification of antibiotics, and role of infection prevention and control (IPC) measures in containment of antimicrobial resistance (AMR). Conclusions. There is a need to sensitize and educate clinicians on various issues related to antimicrobial use such as antibiograms, double anaerobic cover, IPC practices and guideline-based recommendations to curb the AMR pandemic.

Increasing HIV drug resistance (DR) among children with HIV (CHIV) on antiretroviral treatment (ART) is concerning. CHIV ages 1-14 years enrolled March 2019 to December 2020 from five facilities in Kisumu County, Kenya were included. Children were randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load (POC VL) testing every three months with targeted genotypic drug resistance testing (DRT) for VF (&gt; 1000 copies/ml)). A multidisciplinary committee reviewed CHIV with DRT results and offered treatment recommendations. We describe DR mutations and present logistic regression models to identify factors associated with clinically significant DR. We enrolled 704 children in the study; median age was 9 years (interquartile range (IQR) 7,12), 344 (49%) were female and median time on ART was 5 years (IQR 3, 8). During the study period, 106 (15%) children had DRT results (84 intervention and 22 control). DRT detected mutations associate with DR in all participants tested, with 93 (88%) having major mutations, including 51 (54%) with dual class resistance. A history of VF in prior 2 years (adjusted odds ratio (aOR) 11.1; 95% confidence interval (CI) 6.3, 20.0) and less than 2 years on ART at enrollment (aOR 2.2; 95% CI 1.1, 4.4) were associated with increased odds of major DR. DR is highly prevalent among CHIV on ART with VF in Kenya. Factors associated with drug resistance may be used to determine which children should be prioritized for DRT.

The rise of antibiotic-resistant strains of clinically important pathogens is a major threat to global health security. The World Health Organization (WHO) has recognized the urgent need to develop alternative treatments to address the growing list of priority pathogens. Antimicrobial peptides (AMPs) rank among the various suggested options with proven activity and a high potential to be developed into effective agents. Many AMPs are naturally produced by living organisms and protect the host against pathogens as a part of their innate immunity. Various mechanisms associated with their antimicrobial actions include cell membrane disruption, cell wall weakening, protein synthesis inhibition, and interference in nucleic acid dynamics that can induce apoptosis and necrosis. Acinetobacter baumannii is considered a critical pathogen, and severe clinical problems have appeared with isolates resistant to current antibiotic treatments and conventional control procedures such as UV light, disinfectants, and drying. Here, we review the natural AMPs representing the primary candidates for new anti-A. baumannii drugs in a post-antibiotic era and present the use of computational tools to develop the next generation of AMPs with greater microbicidal activity and reduced toxicity.

SARS-CoV-2 pandemic caused an increase in Intensive Care Unit (ICU) hospitalizations with rise in morbidity and mortality; nevertheless, there is still little evidence of pandemic impact on antibiotic resistance in ICU. Retrospective monocentric epidemiological study. All microorganisms isolated from all patients admitted to E.O. Galliera ICU from January 2018 to December 2022 were included. Antibiotic resistance (AR) profiles were evaluated. Aim of the study was to describe and analyze the impact of SARS-CoV-2 pandemic on ICU microorganisms resistance patterns. 1,771 microorganisms identified, 221 (12.47%) had resistant pattern (Resistant Organisms; ROs) isolated from 1,679 patients during 12,030 hospitalization days. The majority of ROs were Gram-negative (79.66% 2018, 77.29% 2019, 61.83% 2020, 62.56% 2021, 60.75% 2022), but increase of Gram-positive microorganisms was observed (20.34% to 39.25% between 2018-2022). Prevalence of AR was: 19.44% 2018, 11.54% 2019, 38.04% 2020, 34.15% 2021, 39.29% 2022 for Gram-positives; 19.86%, 13.56%, 18.12%, 12.41%, 12.31% for Gram-negatives. Incidence of Ros showed COVID-related rise in 2020-2021, followed by a lowering trend since 2021, with new rise in 2022. Possible explanations are antibiotic overtreatment and drop of containing measures. Interesting finding is the cumulative lowering trend of carbapenem resistant K. pneumoniae and P. aeruginosa probably due to different patient features.

Salvia hispanica (chia) is a highly nutritious food source and has gained popularity due to its high omega-3 fatty acid content. Red spider mites are a serious problem in the production of S. hispanica. However, no study has been conducted to analyse the defensive response to the infestation of red spider mites in S. hispanica. To elucidate the molecular mechanisms of the defensive response of S. hispanica to red spider mites, we performed a transcriptomic analysis of S. hispanica when infested by red spider mites. In the comparative assessment of leaf transcriptomes, a total of 1743 differentially expressed genes (DEGs) were identified between control and mite-infested S. hispanica. From these, 1208 (69%) transcripts were up-regulated and 535 (31%) were down-regulated. The DEGs included transcription factors, defense hormones, and secondary metabolites that were either suppressed or activated in response to spider mite herbivory. Gene Ontology (GO) enrichment analysis revealed that plant secondary metabolites such as glucosinolates, and signalling pathways, including the jasmonic acid signalling pathway, may play an important role in the defence against red spider mites. This study provides novel insights into the defence response of S. hispanica in response to insect herbivory and could be a resource for the improvement of pest resistance in the chia.

Background: Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are accurately detected late in the progressive form of the disease. Methods: Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. Results: In the apparently macroscopically unchanged tegument, photon microscopy revealed both progressive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. Conclusions: The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Insulin resistance, as a common pathological process of many metabolic diseases, including diabetes and obesity, has attracted much attention due to its relevant influencing factors. To date, studies have mainly focused on the mechanisms between mitochondrial stress and insulin resistance, and they are now pursued as a very attractive therapeutic target due to their extensive involvement in many human clinical settings. In view of the complex pathogenesis of diabetes, natural drugs have become new players in diabetes prevention and treatment because of their wide targets and few side effects. In particular, plant phenolics have been paid more attention because of their close relationship with oxidative stress. In this review, we briefly review the mechanisms by which mitochondrial stress leads to insulin resistance. Moreover, we list some cytokines and genes that have recently been found to play roles in mitochondrial stress and insulin resistance. Furthermore, we describe several natural drugs that are currently widely used and give a brief overview of their therapeutic mechanisms. Finally, we suggest possible ideas for future research related to the unique role that natural drugs play in the treatment of insulin resistance through the above targets.

Pneumonia kills over two million children under-age of five every year. Oral amoxicillin was recommended by WHO as the first drug of choice for treatment of non-severe pneumonia. The study aimed to determine the clinical failure rate of amoxycillin for the treatment of childhood non-severe pneumonia at Primary Health Care Centers (PHCCs). A randomized controlled multicenter-trial study was conducted in Sana’a. IMCI strategy was used to enrollments the cases where randomly allocated to receive amoxicillin or co-trimoxazole orally for five days. Multivariate logistic regression was used for identified risk factors associated with clinical failure. A total of 254 children were enrolled, of whom 128 cases were treated with amoxicillin while 126 with co-trimoxazole. The clinical failure for amoxicillin was significantly more than co-trimoxazole (30% vs 10%) p value > 0.001. the most risk factor which significantly associated to amoxicillin failure were pre-infection in the last 6 months, while abnormal CBC and literate mothers were associated with clinical failure of co-trimoxazole (p value > 0.05). The use of co-trimoxazole as an alternative to amoxicillin for the treatment of non-severe pneumonia in the PHCCs and conducting further studies to determine the appropriate antibiotic as the first line of defense are recommended.

Carbapenems have long been considered as treatment of choice for Gram-Negative Bacteria (GNB) infections, and today the clinical utility of this class is threatened by the emergence and spread of resistance favored by its increasing use. According to the WHO, Acinetobacter baumannii, nosocomial infection agent, tops the list of priority antibiotic-resistant pathogens, considered to be the most risky for humans. This study sought to determine the prevalence of Acinetobacter baumannii strains producing carbapenemases in four health facilities in the Center and Littoral regions of Cameroon and the associated risk factors. An analytical cross-sectional study was conducted over a six-month period from January to June 2022. All Acinetobacter baumanii or suspected strains isolated from pathological samples at the bacteriology laboratory of different health facilities were systematically collected and underwent a re-identification. After successfully subculturing and growing on nutrient agar, re-identification and antimicrobial susceptibility Testing (AST) were performed using the VITEK 2 System and the Kirby-Bauer method according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Detection and phenotypic characterization of carbapenemases was performed according to adequate standard procedures. A total of 168/226 clinical isolates of Acinetobacter baumannii were confirmed after re-identification of which 52.69% came from male patients, and 55.09% from participants aged between 10-39 years old and 46.71% from pus samples. A very high resistance rates to all families of antibiotics was noted except to colistin (10.2%). About 40.12% of these strains produced carbapenemases with 62.69% of class B and 37.31% of class A. In addition, frequent hospitalisation was significantly associated to the production of carbapenemase among Acinetobacter baumanii (Ajusted-OR=16.53, P-value<0.0001). This study highlighted the emergence of carbapenemase-producing Acinetobacter baumannii which is increasingly growing. Continuous drug-resistant monitoring and preventive measures could help to prevent and curb the dissemination of A.baumanii resistance genes, especially in hospital settings.

Antibiotic resistance is a major public health issue that requires a multifaceted approach. One potential source of antibiotic-resistant bacteria is wastewater in developing countries, which often lacks proper treatment infrastructure and can release high levels of antibiotics and antibiotic-resistant bacteria into the environment. This review article summarizes current knowledge on strategies to combat antibiotic resistance in wastewater in developing countries. Our review highlights the importance of improving wastewater treatment infrastructure to effectively remove antibiotics and antibiotic-resistant bacteria, implementing measures to reduce the release of antibiotics into the environment, and monitoring and surveillance to track the presence and spread of antibiotic-resistant bacteria in wastewater. We also discuss the potential challenges and barriers to implementing these strategies and the need for further research to determine their effectiveness in real-world settings. Overall, this review highlights the need for a comprehensive approach to address antibiotic resistance in wastewater in developing countries and underscores the importance of addressing this issue to protect public health.

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

Bacteriophages have been recognized as potential biocontrol agents in the food industry. Bacteriophages have been proposed for a variety of applications within this industry including bio preservation, pathogen detection, and as an alternative treatment method to antibiotics in animal health. The potential applications of bacteriophages are widespread throughout the entire food production process and serve to enhance food quality, prevent foodborne illnesses, and enhance the efficiency of production. The ability of bacteriophages to lyse bacterial targets with high specificity and pose no threat to mammalian cells or natural microbiota is unique and relevant in terms of suitability for food safety. This review will outline potential and current applications of bacteriophages and their respective impacts on the field.

Background: Patients hospitalized in the intensive care unit (ICU) have a higher susceptibility to infections. Respiratory infections are the most common nosocomial infections. Rising antibiotic resistance due to indiscriminate use of antibiotics and poor adherence to standard precaution in healthcare facilities compounds the problem. The main aim of this study is to assess microbial patterns and antibiotic resistance from bronchoalveolar lavage specimens in severe pneumonia patients. Methods: This retrospective study was conducted in an Indonesian tertiary care hospital from January 2016-December 2020. Written and verbal informed consent was obtained prior to bronchoscopy procedures. Patients were enrolled if they had severe community-acquired pneumonia (CAP) according to American Thoracic Society (ATS)/Infectious Disease Society of America (IDSA) criteria, had high-risk hospital-acquired pneumonia (HAP), late-onset ventilator-associated pneumonia (VAP), or pneumonia caused by Coronavirus disease (COVID-19). Respiratory specimens via bronchoscopy were inoculated on general semi-sloid thioglycolate media. Testing for antibiotic susceptibility was done using the disk diffusion method. Results: Two hundred and one patients’ data were analyzed. The majority of patients were males (65,17%) and above 60 years of age. The most common type of pneumonia was CAP (39,3%). Neurologic/cerebrovascular disease was the most common comorbidity (35,32%). Acinetobacter baumannii was the most frequently isolated microorganism. Ampicillin/sulbactam and amikacin were found to yield lower microbial resistance. Conclusion: Combination of ampicillin/sulbactam and amikacin appeared effective as initial empirical therapy in severe pneumonia patients. Further studies are needed to evaluate the feasibility and effectiveness of this combined therapy.

Antimicrobial resistance (AMR) is one of the top 10 threats affecting global health. AMR defeats the effective prevention and treatment of infections caused by microbial pathogens including bacteria, parasites, viruses and fungi (WHO). Microbial pathogens have natural tendency to evolve and mutate over time resulting in AMR strains. The set of genes involved in antibiotic resistance also termed as “antibiotic resistance genes” (ARGs) spread through species by lateral gene transfer thereby causing global dissemination. While this biological mechanism is prevalent in the spread of AMR, human methods also augment through various mechanisms such as over prescription, incomplete treatment, environmental waste etc. A considerable portion of scientific community is engrossed in AMR related work trying to discover novel therapeutic solutions for tackling resistant pathogens. Comprehensive inspection of the literature shows that diverse therapeutic strategies have evolved over recent years. Collectively, these therapeutic strategies include novel small molecules, newly identified antimicrobial peptides, bacteriophages, phytochemicals, nanocomposites, novel phototherapy against bacteria, fungi and virus. In this work we have developed a comprehensive knowledgebase by collecting alternative antimicrobial therapeutic strategies from literature data. We have used subjective approach for datamining new strategies resulting in broad coverage of entities and subsequently add objective data like entity name, potency, safety information etc. The extracted data was organized KOMBAT (Knowledgebase Of Microbes’ Battling Agents for Therapeutics). A lot of these data are tested against AMR pathogens. We envision that this database will be noteworthy for developing future therapeutics against resistant pathogens. The database can be accessed through http://kombat.igib.res.in/.

Ovarian cancer (OC) represents the most common and lethal gynecologic malignancy, due to its increased incidence and mortality rate. It is usually diagnosed in advanced stages and, even though surgery and platinum-based treatment are initially efficient, recurrences emerge in over 70% of cases. Although there are multiple options of chemotherapy drugs from which to choose, little is known regarding the best strategy for prolonged survival. Thus, the aim of this study was to assess the effect that most frequently used chemotherapeutic regimens have upon time-to-treatment-failure (TTF) from the first line and beyond, considering clinical and biological factors which influence the treatment outcome of platinum-resistant recurrent OC. We retrospectively analyzed data from 78 patients diagnosed with platinum-resistant OC, who underwent chemotherapy-based treatment with or without anti-angiogenic therapy at OncoHelp Oncology Center, Romania (January 2016 - February 2021). Our study identified positive predictive factors for TTF related to anthropometry (age over 60 for patients treated with topotecan with or without bevacizumab), renal function (creatinine levels between 0.65 and 1 mg/dl for patients treated with regimens containing bevacizumab and pegylated liposomal doxorubicin) and treatment choice (bevacizumab in combination with pegylated liposomal doxorubicin or topotecan used from the first line and beyond).

Objective In this study, we aim to synthesize some evidence on the impacts that COVID-19 is having on the epidemiology of Antimicrobial Resistance (AMR) in Africa since it was declared global pandemic by WHO in March 2020. Methodology A scoping review was undertaken by collecting and curating relevant resources from peer-reviewed articles and also from the gray literature. Mixed approaches of extracting data (qualitative and quantitative) were employed in synthesizing evidence, as suggested by Health Evidence Network (HEN). Findings A model constructed based on the synthesis of early evidences available on the effects of factors linked to COVID-19 in impacting the evolution of AMR in Africa predicted that, in cumulative terms, those factors favoring the evolution of AMR outpace those disfavoring it by no less than three folds. Conclusion COVID-19 is fueling the evolution of AMR almost unhindered in Africa. Due recognition of this crisis, concerted efforts for resource mobilization and global cooperation are needed to tackle it.

Endocrine therapy (ET) has established itself as an efficacious treatment for estrogen receptor-positive (ER+) breast cancers, with a reduction in recurrence rates and increased survival rates. The pre-surgical approach with chemotherapy (NCT) has become a common form of management for large, locally advanced or high-risk tumors. However, a good response to NCT is not usually expected in ER+ tumors. Good results with primary ET, mainly in elderly women, have encouraged studies in other stages of life, and nowadays neoadjuvant endocrine treatment (NET) has become a useful approach to many ER+ breast cancers. The aim of this review is to provide an update on the current state of art regarding the present and the future role of NET.

To examine the hydrophobicity of torrefied wood fuel, the water resistances of torrefied pellets prepared by two different methods were evaluated using exposure tests under indoor and outdoor conditions. Torrefied pellets from the xylem of Japanese cedar (Sugi, Cryptomeria japonica) and oak (Konara, Quercus serrata) were prepared by two methods: the torrefaction of wood chips followed by pelletization and the pelletization of wood chips followed by torrefaction. It was found that the pellets prepared by pelletization followed by torrefaction had much lower moisture levels than those prepared by the other method and they showed almost no change in diameter after an outdoor weathering test. These characteristics are unique and indicate that the pellets can be applied not only for industrial use but also for residential and commercial purposes.

Randomized clinical trials represent the gold standard in therapeutic research. Nevertheless, observational cohorts of patients treated for multidrug-resistant (MDR) or rifampin-resistant (RR) tuberculosis (TB) also play an important role in generating evidence to guide MDR/RR TB Generally, summary exposure classifications (e.g., ‘ever versus never’, ‘exposed at baseline’) have been used to characterize drug exposure, in the absence of detailed longitudinal data on MDR-TB regimen These summary classifications, along with an absence of data on covariates that change throughout the course of treatment, constrain researchers’ ability to answer the most relevant questions while accounting for known This paper highlights the importance of regimen changes in improving inference from observational studies of longer MDR-TB treatment regimens and offers an overview of the data and analytic strategies required to do

Glucocorticoids promote muscle atrophy by inducing a class of proteins called atrogenes, resulting in reductions in muscle size and strength. In this work, we evaluated whether a mouse model with pre-existing diet-induced obesity had altered glucocorticoid responsiveness. We observed that all animals treated with the synthetic glucocorticoid dexamethasone had reduced strength, but that obesity exacerbated this effect. These changes were concordant with more pronounced reductions in muscle size, particularly in Type II muscle fibers, and potentiated induction of atrogene expression in the obese mice relative to lean mice. Furthermore, we show that the reductions in lean mass do not fully account for the dexamethasone-induced insulin resistance observed in these mice. Together these data suggest that obesity potentiates glucocorticoid-induced muscle atrophy.

The probability of the evolution of a character depends on two factors: the probability of moving from one character state to another character state and the probability of the new character state fixation. More the evolution of a character is probable more convergent evolution will be witnessed, consequently, convergent evolution could mean that the convergent character evolution result as a combination of these two factors. We investigate this phenomenon by studying the convergent evolution of biochemical functions. We use for the investigation the case of β-lactamases. β-lactamases hydrolyzes β-lactams which are antimicrobials able to block the DD-peptidases involved in bacterial cell wall synthesis. β-lactamase activity is present in two different superfamilies: the metallo-β-lactamase and the serine β-lactamase superfamily. The mechanism used to hydrolyze the β-lactam is different for the two superfamilies. We named this kind of evolution an allo-convergent evolution. We further show that the β-lactamase activity evolved several times within each superfamily, a convergent evolution type that we named iso-convergent evolution. Both types of convergent evolution can be explained by the two evolutionary mechanisms discussed above. The probability of moving from one state to another is explaining the promiscuous β-lactamase activity present in the ancestral sequences of each superfamily, while the probability of fixation is explained in part, by positive selection as the organisms having β-lactamase activity allows them to resist to organism secreting β-lactams. Indeed a mutation increasing the β-lactamases activity will be selected as the organisms having this activity will have an advantage over the others.

Background: Activation of the immune-inflammatory response system (IRS) and the compensatory immune-regulatory system (CIRS) play a key role in SCZ and treatment resistant SCZ. There are only few data on immune and endogenous opioid system (EOS) interactions in SCZ and treatment resistant SCZ.Aim of the study: We examined serum β-endorphin, endomorphin-2 (EM2), mu-opioid (MOR) and kappa-opioid (KOR) receptors, and interleukin (IL)-6 and IL-10 in 60 non responders to treatment (NRTT), 55 partial RTT (PRTT) and 43 normal controls.Results: Serum EM2, KOR, MOR, IL-6 and IL-10 were significantly increased in SCZ as compared with controls. β-endorphin, EM2, MOR and IL-6 were significantly higher in NRTT than in PRTT. There were significant correlations between IL-6, on the one hand, and β-endorphin, EM2, KOR, and MOR, on the other, while IL-10 was significantly correlated with MOR only. A large part of the variance in negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation and formal thought disorders was explained by the combined effects of EM2 and MOR with or without IL-6 while increased KOR was significantly associated with all symptom dimensions. Increased MOR, KOR, EM2 and IL-6 were also associated with neurocognitive impairments including in episodic, semantic and working memory and executive functions.Conclusion: The EOS contributes to SCZ symptomatology, neurocognitive impairments and a non-response to treatment. In SCZ, EOS peptides/receptors may exert CIRS functions, whereas increased KOR levels may contribute to the pathophysiology of SCZ and EM2 and KOR to a non-response to treatment.

Tomato is the highest-value fruit/vegetable crop worldwide. However, the quality and yield of tomatoes are severely affected by late blight. MicroRNA482s (miR482s) are involved in plant immune system. In this study, miR482c was transiently and stably overexpressed in tomatoes in transgenic plants to explore its mechanism in tomato resistance against late blight. Tomato in transgenic plants transiently overexpressed miR482c displayed larger lesion area than the control plants upon infection. Furthermore, compared with the WT tomato plants, the transgenic tomato plants stably overexpressing miR482c displayed decreased expression of target genes accompanied by lower POD, SOD, and PAL activity activities and higher MDA content, thereby leading to a decline in the ROS scavenging ability and aggravating the damage of lipid peroxidation product accumulation on the cell membrane, eventually enhancing plant susceptibility. This finding indicates that miR482c may act as a negative regulator in tomato resistance by regulating NBS-LRR expression levels and ROS levels.

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

The hydrodynamic results obtained from the permeability of porous materials not only affect the assessment of the stream of the gas flow through those materials but they also refer to the loss of pressure energy in that flow. The direct measure of that loss is flow resistances.The results of experimental research upon the assessment of the flow resistances of porous materials with respect to gas flow. The research conducted applied to natural materials with an anisotropic gap-porous structure. The tests were carried out on a gas permeability measuring system, adapted to different shapes of porous material samples. The process issue of the total pressure drop on a porous deposit was considered in the Reynolds number category. The coefficient of flow resistance for anisotropic materials was defined and the value of this coefficient was compared to the gas stream and the total pressure drop on the porous bed was experimentally evaluated.

Wastewater treatment plants (WWTPs) are thought to be potential incubators of antibiotic resistance. Persistence of commonly used antibiotics in wastewater may increase the potential for selection of resistance genes transferred between bacterial populations, some of which may pose a threat to human health. In this study, we measured the concentrations of ten antibiotics in wastewater plant influents and effluents, and in surface waters up- and downstream from two Charlotte area treatment facilities. We performed Illumina shotgun sequencing to assay the microbial community and resistome compositions at each site across four time points from late winter to mid-summer of 2016. Antibiotics are present throughout wastewater treatment, and elevated concentrations of multiple antibiotics are maintained in moving stream water downstream of effluent release. While some human gut and activated sludge associated taxa are detectable downstream, these seem to attenuate with distance while the core microbial community of the stream remains fairly consistent. We observe slight suppression of functional pathways in the downstream microbial communities, including amino acid, carbohydrate and nucleic acid metabolism as well as nucleotide and amino acid scavenging. Nearly all antibiotic resistance genes (ARGs) and potentially pathogenic taxa are removed in the treatment process, though a few ARG markers are elevated downstream of effluent release. Taken together, these results represent baseline measurements which future studies can utilize to help to determine which factors control the movement of antibiotics and resistance genes through aquatic urban ecosystems before, during and after wastewater treatment.

Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the WHO Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting in dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. This increasing detection of resistant gonococcal strains may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics, (2) development of new antibiotics and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this Superbug. This has lead the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

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

Saudi Arabia is an oil-reliant nation as a large percentage of its GDP comes from oil resources. Oil dependency leaves a county at the mercy of the international crude market, and a decrease in the price of crude can seriously destabilize the economy of such nations. An example is the case of Venezuela whose dependence on oil caused a national disaster (McCarthy, 2017). As such, the nation’s exports, GDP, and government revenue are primarily dependent on oil revenue, and the recent decrease in the oil prices has decreased Venezuela’s national revenue resulting in economic collapse as well as inflation. A shift from a resource based economy to a knowledge based economy will help Saudi Arabia become less reliant on its oil revenues for its economic stability and growth (Nurunnabi, 2017).

This study examines the impact of the impregnation of fireclay-based conventional (CC) and medium cement castables (MCC) with liquid sodium silicate glass under vacuum conditions. The goal is to assess how this treatment affects physical, mechanical properties, and durability (alkali and thermal shock resistance) of these castables used in biomass combustion boilers, where they are exposed to temperatures up to 1100°C. The research work employs standard test methods to evaluate physical and mechanical properties. Additionally, advanced techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and specific tests for alkali resistance and thermal shock resistance are used. The research findings suggest that impregnation with sodium silicate glass under vacuum significantly enhances the alkali resistance of both CC and MCC castables. This improvement is primarily due to the reduction in porosity and the increase in density. SEM images reveal that impregnated samples are coated with a glassy layer and the pores are partially filled with sodium silicate. Tests for alkali resistance demonstrate the formation of a protective glassy layer (with a thickness of 0.9-1.5 mm) on the castables surfaces, thereby reducing further penetration of alkali into deeper layers of the samples. However, it is important to mention that impregnated refractory castables have reduced resistance to thermal shock cycles.

Patients receiving hemodialysis are at risk of vascular access infections (VAIs) and particularly vulnerable to the opportunistic pathogen Staphylococcus aureus. Hemodialysis patients were also at increased risk of infection during the COVID-19 pandemic. Therefore, this study determined the change in the molecular and antibiotic resistance profiles of S. aureus isolates from VAIs during the pandemic compared with before. 102 S. aureus isolates were collected from VAIs between November 2013 and December 2021. Before the pandemic, 69 isolates were collected, 58%, 39.1%, and 2.9% from arteriovenous grafts (AVGs), tunneled cuffed catheters (TCCs), and arteriovenous fistulas (AVFs), respectively. The prevalence of AVG and TCC isolates changed to 39.4% and 60.6%, respectively, of 33 isolates during the pandemic. Sequence type (ST)59 was the predominant clone in TCC-methicillin-resistant S. aureus (MRSA) and AVG-MRSA before the pandemic, whereas the predominant clone was ST8 in AVG-MRSA during the pandemic. ST59 carrying the ermB gene was resistant to clindamycin and erythromycin. By contrast, ST8 carrying the msrA gene was exclusively resistant to erythromycin. The ST distribution for different VAIs changed from before to during the pandemic. The change in antibiotic resistance rate for different VAIs was closely related to the distribution of specific STs.

Enteric protozoan pathogenic infections significantly contribute to the global burden of gastrointestinal illnesses. Their occurrence is considerable within remote and indigenous communities and regions due to reduced access to clean water and adequate sanitation. The robustness of these pathogens means requirement of harsh treatment methods such as medicinal drugs or antibiotics. However, such treatments impact the gut microbiome, and create dysbiosis, often leading to opportunistic pathogens, anti-microbial resistance, or functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). Recent studies have shown that these impacts do not remain confined to gut, and are reflected across the gut-brain, gut-liver, and gut-lung axes, among others. Therefore, apart from the medicinal treatment, nutritional supplementation is also a key aspect of providing the recovery from this dysbiosis. Future proteins, prebiotics, probiotics, synbiotics, and food formulations offer a good solution to remedy this dysbiosis. Furthermore, the nutritional supplementation also helps to build a resilience against the opportunistic pathogens and potential future infections and disorders that may arise due to the dysbiosis. Systems biology techniques have shown to be highly effective tools to understand the biochemistry of these processes. Systems biology techniques characterises the fundamental host-pathogen interaction biochemical pathways, at various infection and recovery stages. This same mechanism also allows to track the impact of abovementioned treatment methods of gut microbiome remediation. This manuscript is organised in sections delving into system biology approaches and upcoming developments to understand (1) Infection mechanism and current global status; (2) Cross-organ impacts of dysbiosis, particularly within gut-liver and gut-lung axes; (3) Nutritional interventions. It highlights the impact of antimicrobial resistance (AMR) and Multi-drug resistance (MDR) from a perspective of protozoal infections. It also highlights the role of nutritional interventions to add resilience against the chronic problems caused by these phenomena.

This study focuses on enhancing controllable fibrin-based hydrogels for tissue engineering, addressing existing weaknesses. By integrating a novel copolymer, we improve the foundation for cell-based angiogenesis with adaptable structural features. Tissue engineering often faces challenges like waste disposal and nutrient supply beyond the 200 µm diffusion limit. Angiogenesis breaks through this limitation, allowing the construction of larger constructs. Our innovative scaffold combination significantly boosts angiogenesis, resulting in longer branches and more capillary network junctions. The copolymer attached to fibrin fibers enables precise adjustment of hydrogel mechanical-dynamic properties for specific applications. Our material proves effective for angiogenesis, even under suppression factors like suramin. In our study, we prepared fibrin-based hydrogels with and without the copolymer PVP12400-co-GMA10mol%. Using a co-culture system of human umbilical vein endothelial cells (HUVEC) and mesenchymal stem cells (MSC), we analyzed angiogenetic behavior on and within the modified hydrogels. Capillary-like structures were reproducibly formed on different surfaces, demonstrating the general feasibility of three-dimensional endothelial cell networks in fibrin-based hydrogels. This highlights the biomaterial's suitability for in vitro pre-vascularization of biohybrid implants.

In this study, graphite, the most stable form of carbon, was examined for its hexagonal crystalline structure with specific dimensions (ao=2.46 Ǻ; co=6.70 Ǻ). Its framework comprises parallel carbon atom planes forming regular hexagons (side length 1.415 Ǻ) and 120° angles between adjacent atoms. Two structural variations exist: hexagonal symmetry (1-2-1-2-1-2 planes) and rhomboidal symmetry (1-2-3-1-2-3 planes). The research aimed to produce high-density graphite utilizing carbonaceous raw materials. Graphite-based materials often exhibit high porosity, necessitating additional treatments. The study successfully obtained mesophase tar pitch (yield: 45%), a pivotal raw material, and high-density graphite. The resulting graphite underwent characterization for physical properties (apparent and real density, porosity and compression strength), demonstrating conformity with existing literature data.

After the great success of Mobile wallet, the Internet of Things (IoT) leaves the door wide open for consumers to use their connected devices to access their bank accounts and perform routine banking activities from anywhere, anytime and with any device. However, consumers need to feel safe when interacting with IoT-based payment systems, and their personal information should be protected as much as possible. Unlike as usually done in the literature, in this paper, we introduce two lightweight and secure IoT-based payment protocols based on an identity-based signature scheme. We adopt a server-aided verification technique to construct the first scheme. This technique allows to outsource the heavy computation overhead on the sensor node to a cloud server while maintaining the user's privacy. The second scheme is built upon a pairing-free ECC-based security protocol to avoid the heavy computational complexity of bilinear pairing operations. The security reduction results of both schemes are held in the Random Oracle Model (ROM) under the discrete logarithm and computational Diffie-Hellman assumptions. Finally, we experimentally compare the proposed schemes against each other and against the original scheme on the most commonly used IoT devices: a smartphone, a smartwatch and the embedded device Raspberry Pi. Compared with existing schemes, our proposed schemes achieve significant efficiency in the term of communication and computational overheads

The complexity of modern power grids, exacerbated by integrating diverse energy sources, espe-cially inverter-based resources (IBRs), presents a significant challenge to grid operation and plan-ning since linear models fail to capture the intricate IBR dynamics. This study employs the Sparse Identification of Nonlinear Dynamics (SINDy) method to bridge the gap between theoretical un-derstanding and practical implementation in power system analysis. It introduces the novel Volterra-based Nonlinearity Index (VNI) to examine system-level nonlinearity comprehensively. The distinction of dynamics into first-order linearizable terms, second-order nonlinear dynamics, and third-order noise elucidates the intricacy of power systems. The findings demonstrate a fundamental shift in system dynamics as power sources transit to IBRs, revealing system-level nonlinearity compared to module-level nonlinearity in conventional syn-chronous generators. The VNI quantifies nonlinear-to-linear relationships, enriching our comprehension of power system behavior and offering a versatile tool for distinguishing between different nonlinearities and visualizing their distinct patterns through the proposed VIN profile.

Management of urinary tract infection is challenged by increasing antimicrobial re-sistance (AMR) worldwide. In this study we describe the trends in antimicrobial re-sistance of uropathogens isolated from the largest private sector laboratory in Ghana over a five-year period. We reviewed positive urine cultures at the MDS Lancet Laboratories from 2017 to 2021. Proportions of uropathogens with antimicrobial resistance to oral and parenteral antimicrobials recommended by the Ghana standard treatment guidelines were determined. The proportion of multi-drug resistant isolates, ESBL and car-bapenemase-producing phenotypes were determined. Of 94,134 urine specimens submitted for culture, 20,010 (22.1%) were culture positive. Enterobacterales were the commonest group of organisms, E. coli (70.6) being the commonest isolate and Enterococcus spp. the commonest gram positive (1.3%) organisms. Among oral antimicrobials the highest resistance was observed to ciprofloxacin (62.3%) and cefuroxime (60.2) %) and the least resistance to Fosfomycin (1.9%). The least resistance among parenteral antimicrobials was to meropenem ( 0.3%). Highest multi-drug resistance levels were observed among Klebsiella spp. (68.6%) and E. coli (64.0%). ESBL positivity was highest in Klebsiella spp. (58.6%) and E. coli (50.0%). There may be a need to review the Ghana standard treatment guidelines to reflect increased resistance among uropathogens to recom-mended antimicrobials

Polymyxin resistance, determined by mcr genes located on plasmid DNA, currently pose a high epidemiological threat. Non-typhoid Salmonella (NTS) are one of the key pathogens causing diarrheal diseases. Here, we report the isolation and whole genome sequencing of multidrug colistin-resistant/susceptible isolates of non-typhoid Salmonella enterica serovars carries mcr genes. Non-typhoid strains of Salmonella enterica subsp. enterica were isolated during microbiological monitoring of the environment, food, and diarrheal disease patients between 2018 and 2020 in Russia (n=586). mcr-1 genes were detected using a previously developed qPCR assay and whole genome sequencing of mcr positive isolates was performed by both short-read (Illumina) and long-read (Oxford Nanopore) approaches. Three colistin-resistant isolates including two isolates of S. Enteritidis and one isolate of S. Bovismorbificans carried the mcr-1.1 gene located on IncX4 and IncI2 conjugative plasmids, respectively. The phenotypically colistin-susceptible isolate of S. Typhimurium carried a mcr-9 gene on plasmid IncHI2. In conclusion, we present the first three cases of mcr gene carrying NTS isolates detected in Russia with both outbreak and sporadic epidemiological background.

This work aims to explore the impact of side loads, drill-pipe tool-joint (DP-TJ) speed (RPM), and mud type on the austenitic stainless steel SM2535-110 casing wear characteristics. Actual field drill pipe tool joints, casings, and drilling muds are used in this study. The results of the study show that under both types of lubrication, the wear volume increased with radial load and DP-TJ speed. SM2535-110 casing specimens tested under oil-based mud (OBM) lubrication had higher casing wear volumes than those obtained under water-based mud (WBM) lubrication. This unexpected behavior is mainly due to the increase in the surface hardness of the casing specimens tested under WBM. The results also show that the specific wear factor (K) values of specimens tested under WBM are in general 2 to 4 times higher than those obtained under OBM. While K values under WBM increase with both the side load and RPM, those under OBM show a sharp decrease with RPM. This behavior under OBM is due to this lubricant’s higher viscosity and the change of lubrication regime from thin film to thick film lubrication at higher RPM. Scanning electron microscopy (SEM) and the digital microscopic imaging (DMI) of SM235-110 casing specimens show that an aggressive combination of adhesive, abrasive, and plastic deformation was observed under WBM, while the dominant wear mechanism under OBM is abrasive wear.

Financial markets require a great deal of decision making from the investors and market makers. One metric that can help ease the process of decision making is investment risk which can be measured in two parts; systematic risk and idiosyncratic risk. Clear understanding of the volatilities in each risk component can be a powerful signal in recognizing the right assets to maximize the investment returns. In this paper, we focus on the idiosyncratic volatility values and pre-calculate the idiosyncratic volatility values for 31,198 members of NYSE, Amex and Nasdaq markets for the trades occurring between January 1963 and December 2019. Utilizing a subset of dataset, limited to Nasdaq100 index, we consider the application of machine learning techniques in predicting the idiosyncratic volatility values using the raw trade data to explore a data extension option for the future market trade records that have not yet occurred. We offer a deep learning based regression model and compare it with traditional tree-based methods on a small subset of our per-calculated idiosyncratic volatility dataset. Our analytical results show that the performance of the deep learning techniques is much more robust in comparison to that of the traditional tree-based baselines.

This study compares the effects of lecture-based instruction and process-oriented guided inquiry learning (POGIL)-based instruction on the self-efficacy performance of Grade 12 students. A quasi-experimental, pretest-posttest design was adopted to investigate and assess the impact of POGIL-based instruction versus lecture-based instruction on students’ performance as measured by three types of cognitive outcomes; Knowing, Applying and Reasoning (KAR). Two government high schools in Alain were selected as research sites, one for the boys and one for the girls. The total number of participants was approximately 110 students (N=110); 54 were assigned to treatment groups (25 girls and 29 boys), and 56 were assigned to control groups (27 girls and 29 boys). The treatment group was taught a circular motion unit in physics using POGIL-based instruction, while the control group was taught the unit using lecture-based instruction. The study's findings showed statistically significant differences between students of the control group and the treatment group in favour of the latter regarding their science performance, self-efficacy and science-related attitudes. Moreover, positive correlations were found between participants’ performance at the KAR test, self-efficacy and scientific attitudes towards scientific inquiry after the intervention. In conclusion, it is recommended to shift teaching towards POGIL-based instruction due to its positive impact on students’ performance and self-efficacy. It is also suggested to replicate the study to include government and private schools, elementary and high schools, teachers and advisors.

This aim of this study was to investigate the relationships between lifestyle factors, insulin resistance, and male fertility in 73 men with and without insulin resistance. The participants were divided based on insulin resistance status. Their physical activity, diet, perceived stress, sleep quality, libido level, and the duration of sexual abstinence were assessed on the basis of a number of parameters, including indices proposed by the authors. The results highlighted associations between a number of parameters, i.e., micronutrient and vitamin intake, diet quality, body composition, insulin resistance, and the duration of sexual abstinence, and semen quality, as measured by sperm motility. Significantly, the presence or absence of insulin resistance was linked to male fertility. A multivariate model was developed, incorporating parameters such as the Matsuda index, vitamin intake, and sexual abstinence duration, to predict motility scores. The study underscores the negative impact of modern civilization’s lifestyle choices on male fertility. Notably, vitamin and mineral consumption, especially from antioxidant-rich diets like the Mediterranean diet, emerged as key modifiable factors affecting fertility. Routine diagnostics for insulin resistance in fertility-related interventions is recommended. The study also highlights the importance of considering sexual abstinence duration during semen collection for accurate diagnostic results. Future research should focus on validating the proposed multivariate model and exploring the effects of lifestyle modifications, particularly vitamin supplementation, on fertility outcomes in men, especially in the context of insulin resistance.

Pseudomonas aeruginosa infections are the focus of new treatment alternatives due to their frequent development of resistance to antibiotics and formation of biofilms. Recently, emphasis has been placed on combinations of antibiotics with drugs used for different indications. In this study the combined effects of metformin with imipenem, ceftazidime, cefepime, ciprofloxacin and levofloxacin has been investigated. 50 P. aeruginosa isolates isolated from patients with cystic fibrosis come to Gaziantep University Microbiology Laboratory were included in the study. The susceptibilities of the isolates to antibiotics were investigated by the liquid microdilution method and the combined effect of metformin and antibiotics by the chequerboard synergy test. In our study, as a result of the chequerboard synergy test; synergy between ceftazidime and metformin 6%, partial synergistic 22% isolates; while no synergistic effect was detected between cefepime and metformin in any isolate, partially synergy 46%; synergy between imipenem and metformin 4%, partial synergy 10%; synergy between ciprofloxacin and metformin 6%, partial synergy 6%, antagonist effect 2%; synergy was detected between levofloxacin and metformin 2% and a partial synergy was detected 12%. This study shows that metformin could be a potential antibiotic in its current form or in different chemical forms to be produced synthetically.

Abstract: A. baumannii exhibits resilience in harsh environments and progressively develops resistance to diverse antibacterial agents over time. This adaptability poses a significant challenge in treating an infection caused by this bacterium within healthcare settings. The presence of peptidoglycan, a crucial precursor for cell wall synthesis, contributes to this challenge. Peptidoglycan serves not only as a structural support in bacterial cells but also provides protection against adverse environmental conditions. The synthesis of the peptidoglycan layer involves a group of substrates such as N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), within a three-partitioned process occurring in the membrane, periplasmic space, and cytoplasm of each bacterium. Initiated in the cytoplasm and extending to the inner cell membrane, this synthesis starts with the production of nucleotide precursors. The first step involves the synthesis of UDP-GlcNAc, orchestrated by Glm (GlmS, GlmM, and GlmU) enzymes using fructose-6-phosphate. Subsequently, enzymes from the Mur family, namely MurB, MurA, MurD, MurC, MurI, MurF, and MurE, synthesize UDP-N-acetylmuramyl-pentapeptide (UDP-Mpp) from UDP-GlcNAc. Concurrently, on the cytosolic side, the production of membrane-surrounded undecaprenyl phosphate occurs, involving membrane-side proteins MraY and MurG in the biosynthesis of peptidoglycan. This review emphasizes updated information on Mur family proteins, encompassing physicochemical properties, nature of binding site, number and type of binding site residues, functional domain details, three-dimensional structural aspects, and their functions within bacterial cells. Special attention is directed towards their enzymatic role in peptidoglycan biosynthesis due to the limited availability of precursors in the market. Additionally, the review provides a comprehensive summary of existing inhibitors and ongoing efforts in identifying new targeted inhibitors, recognizing these enzymes as potential candidates for antibacterial drug design and discovery.

Antimicrobial resistance (AMR) is a worldwide healthcare problem. Multidrug resistant organisms (MDRO) have the ability to spread quickly owing to their resistance mechanisms. Although colonized individuals are crucial MDRO dispensers, colonizing microbes have the potential to turn pathogenic under certain conditions, leading to symptomatic infections in carriers. Carbapenemase producing Enterobacterales (CPE) are among the most important MDRO involved in infections and colonizations, associating with multiple resistance mechanisms and virulence factors, causing infections with severe outcomes. All research papers identified in the most comprehensive online databases which contained information related to the topic of this article were analyzed, and relevant data was extracted and included. The first information on CPE could be traced back to the mid-2000s, but pertinent data for many African countries was established in the past 5-8 years. Information is presented chronologically for each country. Although no clear conclusions could be drawn for some countries, it was observed that CPE colonizations are present in most African countries and carbapenem-resistance levels are rising. The most common CPE involved are Klebsiella pneumoniae and Escherichia coli, and the most prevalent carbapenemases are NDM-type and OXA-48-type enzymes. Prophylactic measures, such as screening, are required to combat this phenomenon.

The assessment of photovoltaic devices, which convert light energy into electricity, becomes significantly relevant due to the aspiration to reduce pollution on a global scale. In this context, the pursuit of optimizing the efficiency in converting light energy into electrical energy involves exhaustive studies and structural analyses of solar cells, all directed toward achieving this goal. This study introduces a research proposal aimed at analyzing the losses associated with series resistance (Rs). The analysis takes into account each component comprising this resistance, pro-posing a network of resistances that precisely models each of these elements. The aforementioned research focused on simple-structured crystalline silicon cells. During this investigation, the junction depth (xj) of n-p materials was varied with the aim of achieving efficiencies in the range of 12%. However, in the pursuit of this desired efficiency, a significant impact on series resistance was observed when analyzing the I-V curves of the cells obtained in each manufacturing process.

Previously, we reported that metronidazole MICs are not dependent on the expression levels of nim genes in B. fragilis strains; and we also compared the proteomes of metronidazole-resistant laboratory B. fragilis strains to those of their susceptible parent strains. Here, we used RT-qPCR to correlate the expression levels of 18 candidate genes in a panel of selected, clinical nim gene-positive and -negative B. fragilis strains to their metronidazole MICs. Metronidazole MICs were correlated to the expression of certain tested genes. Specifically, lactate dehydrogenase expression correlated positively, whereas cytochrome fumarate reductase/succinate dehydrogenase, malate dehydrogenase, phosphoglycerate kinase redox and gat (GCN5-like acetyltransferase), and relA (stringent response) regulatory gene expressions correlated negatively with metronidazole MICs. This result provides evidence for the involvement of carbohydrate catabolic enzymes in metronidazole resistance in B. fragilis. This result was supported by direct substrate utilization tests. However, the exact roles of these genes/proteins should be determined in deletion–complementation tests. Moreover, the exact redox cofactor(s) participating in metronidazole activation need to be identified.

Rice is an important cereal crop worldwide, the growth of which is affected by rice blast disease, caused by the fungal pathogen Magnaporthe oryzae. As climate change increases the diversity of pathogens, the disease-resistance genes (R genes) in plants must be identified. The major blast-resistance genes have been identified in indica rice varieties; therefore, japonica rice varieties with R genes now need to be identified. Because leucine-rich repeat (LRR) domain proteins possess R-gene properties, we used bioinformatics analysis to identify the rice candidate LRR domain receptor-like proteins (OsLRR-RLPs). OsLRR-RLP2, which contains six LRR domains, showed differences in the DNA sequence, containing 43 single-nucleotide polymorphisms (SNPs) in indica and japonica subpopulations. The results of M. oryzae inoculation analysis indicated that indica varieties with partial deletion of OsLRR-RLP2 showed susceptibility, whereas japonica varieties with intact OsLRR-RLP2 showed resistance. oslrr-rlp2 mutant generated using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) showed increased pathogen susceptibility, whereas plants overexpressing this gene showed pathogen resistance. These results indicate that OsLRR-RLP2 confers resistance to rice, and OsLRR-RLP2 may be useful for breeding resistant cultivars.

Introduction: We under took an in-use evaluation of a novel hypochlorous acid-based hand hygiene product with in vitro sporicidal efficacy in a NHS Older Persons inpatient ward setting. Methods: The novel hand hygiene product was implemented for a trial period of seven weeks commending in September 2023. Healthcare worker (HCW) hands were sampled before and after direct patient care, and after the application of either an alcohol-based handrub (ABHR) (n=50) or the novel product (n=50). Samples were cultured to quantify the total aerobic count (TAC) and presence or absence of MRSA, ESBLs, CREs, and C. difficile. Trends in weekly observational hand hygiene audit results were reviewed, and a survey of HCW views about the new product undertaken. Results: HCW hands had a significantly greater TAC after ABHR (p=0.01) but not after the novel product (p=0.11) compared with their respective baseline counts. 3% of 100 samples grew MRSA or ESBLs after application of the alcohol-based or novel hand hygiene products. No C. difficile was cultured from healthcare worker hands. There was no significant difference in observed hand hygiene compliance. The majority of HCW surveyed preferred the novel product to the alcohol-based hand hygiene product. Discussion: The novel hand hygiene product was more effective than ABHR at reducing the TAC on HCW hands. Poor hand hygiene technique may explain the identification of antibiotic-resistant bacteria on staff hands after ABHR or the novel product. We were not able to evaluate sporicidal efficacy since no C. difficile was cultured from hands.

Clopidogrel, a prescription drug to reduce ischemic events in cardiovascular patients, has been extensively studied in mostly European individuals but not among Caribbean Hispanics. This study evaluated the low abundance and reduced activity of paraoxonase-1 (PON1) in clopidogrel-resistant patients as a predictive risk biomarker of poor responders and disease severity in this population. Thirty-six patients on clopidogrel (cases; divided into poor and normal responders) were enrolled along with 11 cardiovascular patients with no clopidogrel indications (positive control) and 13 healthy volunteers (negative control). Residual on-treatment platelet function (PRU), PON1 abundance by western blotting, and PON1 activity by enzymatic assays were measured. PON1 genotyping and computational haplotype phasing were performed for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p&gt; 0.05). However, a significantly lower enzymatic activity was found in poor responders (10.57 6.79 µU/mL) when compared to controls (22.66 8.30 µU/mL and 22.21 9.66 µU/mL; p= 0.004). PON1 activity among carriers of the most prevalent PON1 haplotype (AA|AA) was significantly lower than in wild-types (7.90 µU/mL vs 22.03 µU/mL; p= 0.005). Our findings suggested that PON1 is a potential biomarker of cardiovascular disease severity in Caribbean Hispanics.

Tungsten and its alloys are considered as a key component in high temperature environment. Self-passivating W-Si-xY alloys with different Y contents made from the powders milled for different times were prepared by mechanical alloying (MA) and spark plasma sintering (SPS). Their microstructures and oxidation resistance were investigated. It is found that the oxidation resistance of the alloys with low Y contents (0Y and 2Y) made from 20 h-milled powders is worse than that of the alloys made from 4 h-milled powders. It is because the protective WO3/SiO2 composite layer is discontinuous. While the alloys with high Y contents (4Y and 6Y) made from 4 h and 20 h-milled powders show good oxidation resistance. Even, the thickness of the oxide layer of the alloys with 4Y and 6Y made from 20 h-milled powders after oxidation at 1000 ℃ for 2 h is 84.0 μm and 70.7 μm, less than that made from 4 h-milled powders. This is due to the size and distribution of W5Si3, Y2Si2O7 aggregates and W-Y-O melt. The synergistic effects of Y contents and milling time on the microstructures and oxidation resistance of the alloys are revealed.

Struts of a superconducting YBa2Cu3Oy (YBCO) foam prepared by the infiltration growth method on the base of commercial polyurethane foams were extracted from the bulk, and thoroughly characterized concerning the microstructure and the magnetoresistance, measured by the four-point technique. Optical microscopy, electron microscopy, electron backscatter diffraction and atomic force microscopy observations indicate an unique microstructure of the foam struts which shows a large amount of tiny Y2BaCuO5 (Y-211) particles (with diameters between 50–100 nm) being enclosed in channel-like grain boundaries between the YBCO grains and an one-of-a-kind surface of the struts covered with Ba3Cu5Oy-particles. The resistance data obtained at temperatures in the range 4.2 K ≤T≤ 150 K (applied magnetic fields ranging from 0 to 7 T) were analyzed in the framework of the fluctuation-induced conductivity (FIC) approach using the Aslamazov-Larkin model. The resulting FIC curves reveal the presence of five distinct fluctuation regimes, namely, the short-wave (SWF), one-dimensional (1D), two-dimensional (2D), three-dimensional (3D), and critical (CR) fluctuation domains. The analysis of the FIC data enable the coherence length in the direction of the c-axis at zero-temperature (ξc(0)), the lower and upper critical magnetic fields (Bc1, Bc2), the critical current density at T= 0 K (Jc(0)) and several other parameters describing the the material’s superconducting properties to be determined. The present data reveal that the minuscule Y-211 particles found along the YBCO grain boundaries alter the excess conductivity and the fluctuation behavior as compared to conventional YBCO samples, leading to a quite high value for Jc(0) for a sample without added flux pinning centers.

In order to improve the wear resistance of copper contacts in high-voltage switches and improve the abnormal discharge phenomenon caused by wear gaps, laser remelting technology was used to strengthen the surface of copper contacts. The surface morphology, microhardness, and wear resistance of the remelted samples were tested and characterized using scanning electron microscopy (SEM), microhardness tester, and friction and wear tester. The test results indicate that laser frequency, pulse width, and current parameters can directly affect the surface morphology and wear resistance of the sample, but their influencing processes vary. The laser frequency is achieved by the variation of the superposition relationship between the impact points, while the pulse width and current are achieved by the variation of the laser intensity at the impact points. When the pulse frequency is 10Hz, the pulse width is 10ms, and the current is 100A, the sample exhibits a more balanced surface morphology, microhardness, and wear resistance.

Bacteria are the major pathogens affecting food safety and foods of animal origin are main vehicles of human illness since food animals are the main reservoirs for many food-borne pathogens. Moreover, emergence and spread of multidrug-resistant food-borne bacterial pathogens become a significant public health concern globally. A cross-sectional study was conducted from October 2019 to July 2021 to estimate the prevalence, identify associated factors, and determine antibiotic resistance pattern of Salmonella species from foods of bovine origin in Dessie and Kombolcha towns. A total of 384 samples were collected. Simple and systematic random sampling techniques were employed for sampling milking cows and carcasses among cattle slaughtered at abattoirs, respectively. Samples from milk tanks, milk products, and beef were also selected randomly. Salmonella species were isolated and identified according to recommended standard bacteriological protocols. All the detected Salmonella species isolates were screened for in vitro antimicrobial susceptibility using agar disc diffusion method against 12 antimicrobial disks. The collected raw data were analyzed using descriptive and inferential analysis techniques. The overall prevalence rate of Salmonella species was 7.0%. The highest prevalence rate of Salmonella species (16.7%) was obtained from milk tank samples but not detected in milk products. Multidrug resistance to three and more than three drugs was observed among all isolated Salmonella species. All Salmonella species isolates (100.0%) were found to be resistant to Erythromycin, Tetracycline, and Vancomycin. The majority of the isolates (96.3%) were also resistant to Doxycycline and Polymyxin B. On the other hand, all isolates (100.0%) were sensitive to Gentamicin and Ciprofloxacin. The detection of multidrug-resistant Salmonella species showed that foods of bovine origin produced in the study sites were not safe for consumption. Hence, preventive measures are required to reduce bacterial contamination, concurrently to improve the wholesomeness and safety of foods of bovine origin.

In recent decades, low-yielding seismic devices based on the use of friction dampers have emerged as an excellent solution for the development of building structures with improved reparability and resilience. Achieving an optimal design for such low-yielding seismic devices requires precise control of bolt preloading levels and predictability of the friction coefficient (CoF) between the damper interfaces. While various types of friction devices exist, capable of providing significant energy dissipation, ongoing research is focused on the development of novel friction materials that exhibit a stable hysteretic response, high CoF values, minimal differences between static and dynamic CoF, and predictable slip resistance. In this context, an experimental campaign was conducted at the STRENGTH Laboratory of the University of Salerno to evaluate the behaviour of new friction shims employing specially developed metal alloys. Specifically, the influence of the characteristics of the contact surfaces in the sliding area on the behaviour and performance of the friction device was analysed. The tests followed the loading protocol recommended by EN12159 for seismic device qualification. Monitored parameters included preloading force values and the evolution of slip resistance. The friction value was determined, along with its degradation over time. Finally, the material's performance in terms of hysteretic behaviour was assessed, providing a comparison of the tested specimens in terms of slip force degradation and energy dissipation capacity.

BiFeO3/La0.7Sr0.3MnO3 (BFO/LSMO) epitaxial heterostructures were successfully synthesized by pulsed laser deposition on (001)-oriented SrTiO3 single crystal substrates with Au top electrodes. Stable bipolar resistive switching characteristics regulated by ferroelectric polarization reversal was observed in the Au/BFO/LSMO heterostructures. The conduction mechanism was revealed to follow the Schottky emission model, and the Schottky barriers in high resistance and low resistance states were estimated based on temperature-dependent current–voltage curves. Further, the observed memristive behavior was interpreted via the modulation effect on the depletion region width and the Schottky barrier height caused by ferroelectric polarization reversal, combining with the oxygen vacancies migration near the BFO/LSMO interface.

Trichoderma spp. are widely used in plant disease control as biocontrol agents. Inducing plant disease resistance is an important biocontrol mechanism of Trichoderma. It is of great significance to explore the factors involved in the surface recognition and interaction of Trichoderma with plants. Hydrophobin is a small molecular protein rich in cysteine in higher filamentous fungi and has been found to participate in the morphogenesis and interaction of fungi with other organisms. In this study, the type II hydrophobic protein-coding gene Thfb6 from T. harzianum TH33 was cloned and heterologously expressed in Escherichia coli BL21 (DE3). The purified recombinant protein Thfb6 induced a hypersensitive response in tobacco leaves, a burst of reactive oxygen species, and an accumulation of callose, phenolic substances, and lignin in tobacco, indicating that Thfb6 can induce an early defense reaction in tobacco. Thfb6 also enhanced the systemic resistance of tobacco against tobacco mosaic virus. The rate of lesion number reduction by treatment with Thfb6 could be up to 36.02%. Thfb6 increased the activity of tobacco defense-related enzymes, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase, and peroxidase, which were all more than three times the control after 3–5 days post treatment of Thfb6. The transcription of resistance-related genes, including the PAL gene, non-expresser of pathogenesis-related gene1 (NPR1), and basic pathogenesis-related gene 1 (PR1-b), were upregulated after Thfb6 treatment. The relative expression levels of the PAL and NPR1 genes were highest on the third and fourth days after Thfb6 treatment, at 5.5 times and 8.3 times that of the control, respectively. The relative expression level of PR1 on the sixth day after Thfb6 treatment was 5.3 times that of the control. These results indicate that the improvement of defense-related enzyme activity and the induced expression of disease-resistance-related genes were the main mechanisms by which Thfb6 induced systemic resistance in tobacco.

The optimized design of catalyst layer (CL) plays a vital role to improve the performance of polymer electrolyte membrane fuel cells (PEMFCs). The need to improve transport and catalyst activity is especially important at low Pt loading, where local oxygen and ionic transport resistances decrease the performance due to an inevitable reduction of active catalyst sites. In this work, local oxygen and ionic transport are analyzed using direct numerical simulation on virtually reconstructed microstructures. Four morphologies are examined: (i) heterogeneous, (ii) uniform, (iii) uniform vertically-aligned, and (iv) meso-porous ionomer distributions. The results show that the local oxygen transport resistance can be significantly reduced, while maintaining good ionic conductivity, through the design of high porosity CLs (ε≃0.6−0.7) with low agglomerated ionomer morphologies. Ionomer coalescence into thick films can be effectively mitigated by increasing the uniformity of thin films and reducing the tortuosity of ionomer distribution (e.g., good ionomer interconnection in supports with a vertical arrangement). The local oxygen resistance can be further decreased by the use of blended ionomers with enhanced oxygen permeability and meso-porous ionomers with oxygen transport routes in both water and ionomer. In summary, achieving high performance at low Pt loading in next-generation CLs must be accomplished through a combination of high porosity, uniform and low tortuosity ionomer distribution, and oxygen transport through activated water.

Fusarium wilt diseases severely influence the growth and productivity of numerous crop plants. The consortium of antagonistic rhizospheric Bacillus strains and quercetin were evaluated imperatively as a possible remedy to effectively manage the Fusarium wilt disease of tomato plants. The selection of Bacillus strains was made based on in-vitro antagonistic bioassays against Fusarium oxysporum f.sp. lycoprsici (FOL). Whereas, quercetin was selected after screening a library of phytochemicals during in-silico molecular docking analysis using tomato LysM receptor Kinases “SILKY12” based on its dual role in symbiosis and plant defense responses. After the selection of test materials, pot trials were conducted where tomato plants were provided consortium of Bacillus strains as soil drenching and quercetin as a foliar spray in different concentrations. The combined application of consortium () and quercetin (1.0 mM) reduced the Fusarium wilt disease index up to 69% also resulting in increased plant growth attributes. Likewise, the imperative application of the Bacillus consortium and quercetin (1.0 mM) significantly increased total phenolic contents and activities of the enzymes of the phenylpropanoid pathway. Non-targeted metabolomics analysis was performed to investigate the perturbation in metabolites. FOL pathogen negatively affected a range of metabolites including carbohydrates, amino acids, phenylpropanoids, and organic acids. Thereinto, combined treatment of Bacillus consortium and quercetin (1.0 mM) ameliorated the production of different metabolites in tomato plants. These findings prove the imperative use of Bacillus consortium and quercetin as an effective and sustainable remedy to manage Fusarium wilt disease of tomato plants and to promote the growth of tomato plants under pathogen stress conditions.

Pancreatic cancer has a poor prognosis with its five-year survival rate lower than that of any other cancer type because it is difficult to detect in the early stages. Gemcitabine, a standard treatment for pancreatic cancer, often has poor outcomes for patients as a result of chemoresistance. Therefore, novel therapeutic targets must be identified to overcome gemcitabine-resistance. Here, we found that SLC38A5, a glutamine transporter, is more highly overexpressed in gemcitabine-resistant patients than in gemcitabine-sensitive patients. Furthermore, the deletion of SLC38A5 decreased the proliferation and migration of gemcitabine-resistant PDAC cells. We also found that the inhibition of SLC38A5 triggered the ferroptosis signaling pathway via RNA sequencing. Also, silencing SLC38A5 induced mitochondrial dysfunction and reduced glutamine uptake and glutathione (GSH) levels, and downregulated the expressions of GSH-related genes NRF2 and GPX4. The blockade of glutamine uptake negatively modulated the mTOR-SREBP1-SCD1 signaling pathway. Therefore, suppression of SLC38A5 triggers ferroptosis via two pathways that regulate lipid ROS levels. Similarly, we observed knockdown of SLC38A5 restored gemcitabine sensitivity by hindering tumor growth and metastasis in the orthotopic mouse model. Altogether, our results demonstrated that SLC38A5 could be a novel therapeutic target to overcome gemcitabine-resistance in PDAC therapy.

In sub-Saharan Africa, sweetpotato weevils are the most devastating pests of cultivated sweetpotato, causing estimated losses of between 60% and 100%, primarily during dry spells. The predominantly cryptic feeding behavior of the Cylas spp within the roots makes their control difficult, thus host plant resistance is one of the most promising lines of protection against these pests. However, progress in breeding for weevil-resistant cultivars has been slow in part due to the complex hexaploid genome of sweetpotato, which complicates conventional breeding in addition to the scarcity of varieties with significant levels of resistance for use as sources of resistance. Pollen sterility, cross incompatibility and poor seed set and germination in sweetpotato are also common challenges to improving weevil resistance. Accurate phenotyping of sweetpotato weevil resistance to enhance efficiency of selection has been equally difficult. Genomics-assisted breeding though in its infancy stages in sweetpotato has the potential application in overcoming some of these barriers. However, it will require the development of more genomic infrastructure; particularly single nucleotide polymorphism markers (SNPs), robust next generation sequencing plat-forms together with relevant statistical procedures for analyses. With the recent advances in genomics, we anticipate that genomic breeding for sweetpotato weevil resistance will be expedited in the coming years. This review sheds light on Uganda's efforts to date to breed against the Cylas puncticollis (Boheman) and Cylas brunneus (Fabricius) species of African sweetpotato weevil.

Acid stress poses a common challenge for bacteria in diverse environments by the presence of inorganic (e.g., mammals’ stomach) or organic acids (e.g., feed additives; acid-based disinfectants). Limited knowledge exists regarding acid-tolerant strains of specific serotypes, clonal lineages, or sources in human/animal pathogens, namely non-typhoidal Salmonella enterica (NTS) and Enterococcus faecium (Efm). This study evaluated acidic pH and peracetic acid (PAA) susceptibility of Efm (n=72) and NTS (n=60) from diverse epidemiological/genetic backgrounds, and with multiple antibiotic resistance profiles. Efm minimum growth/survival-pH was 4,5-5/3-4 and for NTS 4,0-4,5/3,5-4,0. Among Efm, only those of clade-non-A1 (non-hospital associated) or food chain demonstrated greater tolerance to acidic pH compared to clade-A1 (hospital-associated clones) or clinical isolates (P<0.05). MDR (multidrug-resistant) NTS survived better to acidic pH (P<0.05). The MICPAA/MBCPAA was 70-120/80-150mg/L for Efm and 50-70/60-100mg/L for NTS. Efm-clade-A1 or MDR strains exhibited higher PAA tolerance than clade-non-A1 or non-MDR ones (P<0.05). Higher tolerance was found in non-MDR and clinical NTS than in food chain isolates (P<0.05), but not between different serogroups. This unique study identifies specific NTS or Efm populations more tolerant to acidic pH or PAA, emphasizing the need for further research to tailor control measures of public health and food safety within a One Health framework.

The global burden of bacterial resistance remains one of the most serious public health concerns. Infections caused by multiresistant (MDR) bacteria in critically ill patients require immediate empirical treatment, which may not only be ineffective due to the resistance of MDR bacteria to multiple classes of antibiotics, but may also contribute to the selection and spread of antimicrobial resistance. Both the WHO and the ECDC consider carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) to be the highest priority. The ability to form biofilm and the acquisition of multiple drug resistance, in particular to carbapenems, have made these pathogens particularly difficult to treat. They are a growing cause of healthcare-associated infections and a significant threat to public health, associated with a high mortality rate. Moreover, co-colonization with these pathogens in critically ill patients was found to be a significant predictor for in-hospital mortality. Importantly, they have the potential to spread resistance using mobile genetic elements. Given the current situation, it is clear that finding new ways to combat antimicrobial resistance can no longer be delayed. The aim of this review was to evaluate the literature on how these pathogens contribute to the global burden of AMR. The review also highlights the importance of the rational use of antibiotics and the need to implement antimicrobial stewardship principles to prevent the transmission of drug-resistant organisms in healthcare settings. Finally, the review discusses the advantages and limitations of alternative therapies for the treatment of infections caused by these "titans" of antibiotic resistance.

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

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

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