Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

A simple, isocratic and robust RP-HPLC method for the analysis of azithromycin was developed, validated and applied for the analysis of bulk samples, tablets and suspensions. The optimum chromatographic conditions for separation were established as mobile phase comprising of acetonitrile-0.1M KH₂PO₄ pH 6.5-0.1M tetrabutyl ammonium hydroxide pH 6.5-water (25:15:1:59% v/v/v/v) delivered at a flow rate of 1.0 ml/min. The stationary phase consisted of reverse-phase XTerra^® (250 mm× 4.6 mm i.d., 5 µm particle size) maintained at a temperature of 43 °C with a UV detection at 215 nm. The method was found to be linear in the range 50-150% (r²=0.997). The limits of detection and quantification were found to be 0.02% (20 µg) and 0.078% (78 µg) respectively with a 100.7% recovery of azithromycin. Degradation products of azithromycin in acidic and oxidative environments at 37 °C were resolved from the active pharmaceutical ingredient and thus the method is fit for the purpose of drug stability confirmation.

In the dynamic landscape of drug discovery, Computer-rAided Drug Design (CADD) emerges as a transformative force, bridging the realms of biology and technology. This paper overviews CADD's historical evolution, categorization into structure-based and ligand-based approaches, and its crucial role in rationalizing and expediting drug discovery. As CADD advances, incorporating diverse biological data and ensuring data privacy become paramount. Challenges persist, demanding the optimization of algorithms and robust ethical frameworks. Integrating Machine Learning and Artificial Intelligence amplifies CADD's predictive capabilities, yet ethical considerations and scalability challenges linger. Collaborative efforts and global initiatives, exemplified by platforms like Open Source Malaria, underscore the democratization of drug discovery. The convergence of CADD with personalized medicine offers tailored therapeutic solutions, though ethical dilemmas and accessibility concerns must be navigated. Emerging technologies like quantum computing, immersive technologies, and green chemistry promise to redefine the future of CADD. The trajectory of CADD, marked by rapid advancements, anticipates challenges in ensuring accuracy, addressing biases in AI, and incorporating sustainability metrics. The paper concludes by highlighting the need for proactive measures in navigating the ethical, technological, and educational frontiers of CADD to shape a healthier, brighter future in drug discovery.

The target of an antibody plays a significant role in the success of antibody-based therapeutics and diagnostics, and to an extent, that of vaccine development. This importance is focussed on the target binding site – epitope, where epitope selection as a part of design thinking beyond traditional antigen selection using whole cell or whole protein immunisation can positively impact success. With purified recombinant protein production and peptide synthesis to display limited/selected epitopes, intrinsic factors that can affect the functioning of resulting antibodies can be more easily selected for. Many of these factors stem from the location of the epitope that can affect accessibility of the antibody to the epitope at a cellular or molecular level, direct inhibition of target antigen activity, conservation of function despite escape mutations, and even non-competitive inhibition sites. Through the incorporation of novel computational methods for predicting antigen changes to model-informed drug discovery and development, superior vaccines and antibody-based therapeutics or diagnostics can now be more easily designed to mitigate failures. With detailed examples, this review highlights the new opportunities, factors and methods of predicting antigenic changes for consideration in sagacious epitope selection.

We evaluated performance of two American surveillance systems for monitoring the spread of antimicrobial-resistant (AMR) gonorrhea: the Gonococcal Isolate Surveillance Project (GISP) and the enhanced Gonococcal Isolate Surveillance Project (eGISP) which includes the non-urethral isolates in addition to the urethral ones utilized in the original surveillance system. A continuous-time agent-based model of gonorrhea transmission among the US men who have sex with men (MSM) population was developed and used for this purpose. The model accounts for susceptible and resistant strains of N. gonorrhoeae, symptomatic and asymptomatic infection and different transmission routes. Overall, eGISP system outperforms the original GISP system and allows to obtain a higher accuracy using a significantly lower number of isolates. Most of time, the original surveillance system determines the moment of switch to a new antibiotic later than necessary which leads to additional gonorrhea cases and spread of the resistance. Informing the gonorrhea treatment guidelines by eGISP estimates instead of the currently used GISP estimates would result in reduction of 622 (95% uncertainty interval: -4,009, 9,099) gonorrhea cases in the simulated cohort of 10,000 US MSM over a 25-year period without reduction in the lifespan of the current first-line antibiotic.

Multiple lines of research have led to the hypothesis that antimicrobial peptides (AMPs) are an important component of the innate immune response, playing a vital role in the defense against a wide range of infectious diseases. In this review we explore the occurrence and availability of antimicrobial proteins and peptides across various species, highlighting their natural abundance and evolutionary significance. The design of AMPs has been driven by the identification of key structural and functional features, which are essential for optimizing their antimicrobial activity and reducing toxicity to host cells. We discuss various approaches, including rational design, high-throughput screening, and computational modeling, that have been employed to develop novel AMPs with enhanced efficacy. A particular focus is given to the identification and characterization of peptide fragments derived from naturally occurring host defense proteins, which offer a promising avenue for the discovery of new AMPs. The incorporation of artificial intelligence (AI) and machine learning (ML) tools into AMP research has further accelerated the identification, optimization, and application of these peptides. This review also discusses the current status and therapeutic potential of AMPs, emphasizing their role in addressing the growing issue of antibiotic resistance. The conclusion highlights the importance of continued research and innovation in AMP development to fully harness their potential as next-generation antimicrobial agents.

Background: Bacterial resistance to several antibiotic classes is seen as a grave threat worldwide. Bacterial resistance to antibiotics was mostly caused by the abuse and overuse of antibiotics, particularly penicillins and first-generation cephalosporins, in Egypt's primary healthcare facilities. Aim of the study: To investigate the main resistant bacteria to a few chosen penicillins and first-generation cephalosporins, as well as the characterization of these antibiotics' resistant genes and their detrimental effects in Egypt's main medical facilities. Methodology: Two hundred respiratory and urinary tract infection (RTI and UTI) specimens were gathered from Egyptian primary medical center patients. The turbidimetric assay at 630 nm wavelength, the broth dilution technique, and the nanopore sequencing homology approach were used to characterize the major resistant pathogenic bacteria and their resistant genes to cefadroxil (first generation cephalosporins) and nafcillin (antipseudomonal penicillin). Moreover, adverse outcomes resulting from antibiotic resistance were noted. Results: Out of 200 specimens with RTI and UTI, 186 samples showed the proliferation of resistant bacteria isolates. Enterococcus faecium strain NFC and Staphylococcus aureus strain CDX were among them. Nanopore sequencing confirmed that the antibiotic-resistant gene in Enterococcus faecium was the NFC gene, whereas the antibiotic-resistant gene in Staphylococcus aureus was the CDX gene. Penicillin-binding proteins with modest affinity were encoded by both genes. These bacterial resistance patterns were linked to a low death rate of 5% and a high morbidity rate of 47%. Conclusion: By expressing low-affinity penicillin-binding proteins through resistant NFC and CDX genes, Enterococcus faecium strain NFC and Staphylococcus aureus strain CDX were found to be the predominant bacterial isolates that cause antibiotic resistance to first-generation cephalosporins and penicillins.

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with efficacy against some NNRTI resistant mutants. Although DOR resistance mutations are established for HIV-1 subtype B, it is less clear for non-B subtypes. This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others didn’t significantly impact DOR susceptibility. We observed agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y188L caused high-level resistance, in agreement with the predictions. These mutations are frequently observed in patients failing efavirenz or nevirapine-based first-line regimens. However, they are also observed in those failing a protease inhibitor-based second-line regimen, as we have observed in our database. Genotypic drug resistance testing is therefore vital prior to initiation on DOR-based treatment for those previously exposed to efavirenz or nevirapine.

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 on 512 DNA specimens for two genetic loci (rs662 and rs854560). No statistical differences in mean relative PON1 abundance were found among the groups (p> 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.

Colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide and is responsible for numerous deaths. 5-fluorouracil (5-FU) is an effective chemotherapy drug commonly used in the treatment of CRC, either as monotherapy or in combination with other drugs. However, half of CRC cases are resistant to 5-FU-based therapies. To contribute to the understanding the mechanisms underlying CRC resistance or recurrence after 5-FU-based therapies, we performed a comprehensive study integrating in silico, in vitro and in vivo approaches. We identified differentially expressed genes and enrichment of pathways associated with recurrence after 5-FU-based therapies. Using these bioinformatic data as a starting point, we selected a group of drugs that restored 5-FU sensitivity to 5-FU resistant cells. Interestingly, treatment with the novel Rac1 inhibitor, 1A-116, reversed morphological changes associated with 5-FU resistance back to a control-like status. Moreover, our in vivo studies have shown that 1A-116 affected tumor growth and the development of metastasis. All our data allowed us to postulate that targeting Rac1 represents a promising avenue for the development of new therapies for patients with CRC resistant to 5-FU-based therapies.

Soluble inorganic pyrophosphatase (sPPase), a pyrophosphate hydrolase, has been shown to play an important role in several physiological processes such as plant growth and development, metabolic activities, and response to abiotic stresses, but sPPase has been less studied in woody plants. In order to preliminarily verify whether the soluble inorganic pyrophosphatase in Eucommia ulmoides Oliver (E. ulmoides) has a role in resistance to drought stress, we amplified the EuSIP5 (E. ulmoides soluble inorganic pyrophosphatase 5) cDNA sequence from E. ulmoides by RT-PCR. In order to study the drought resistance of the Eucommia ulmoides soluble inorganic pyrophosphatase 5 (EuSIP5) gene, the cDNA sequence of the EuSIP5 gene was amplified from Eucommia ulmoides Oliver by RT-PCR. Bioinformatic analysis indicated that EuSIP5 might be an unstable amphipathic protein, mainly located in the cytoplasm. E. ulmoides, the highest expression of the EuSIP5 gene was found in male leaves and pericarp from April to October, and in leaves of E. ulmoides in July and September. During drought, the expression of EuSIP5 in seedling E. ulmoides leaves was significantly higher than that of the control. An overexpression vector harboring the EuSIP5 was constructed and introduced into the tobacco (Nicotiana tabacum cv. Xanthi). We found that during drought stress, the appearance of wilting was delayed by 4 days in transgenic tobacco plants (OE) compared with wild type plants (WT), and the expression of drought-related genes DET2, CYP85A1, P5CS, ERF1 and F-box was found to be increased in transgenic tobacco leaves, as well as the enzyme activities of the protective enzymes: peroxidase (POD), superoxide dismutase (SOD) and catalase (CAT) were significantly higher than those of the WT, and the malondialdehyde (MDA) content was lower than the WT. These results indicated that the introduction of EuSIP5 gene into tobacco increased the expression of drought-related genes, enhanced the anti-membrane oxidation ability of tobacco, and reduced the oxidative stress damage, thus improving the drought resistance of tobacco.

Background: Cardiometabolic risk factors (CRFs) are significant health concerns among adults with overweight and obesity. Resistance training (RT) is known to manage CRFs, but the impact of moderate-frequency RT (two to three times weekly) remains unclear. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing moderate-frequency RT with non-exercise control or usual care in overweight and obese adults. Searches were performed in PubMed, Web of Science, EMBASE, and Cochrane Library up to February 2024, following the PRISMA 2020 guidelines. Eligible studies included non-athletic adults (BMI ≥ 25) aged 18 years or older, with RT interventions lasting 7 weeks or longer. Results: Fifteen RCTs were included. Moderate-frequency RT significantly reduced systolic blood pressure by -4.66 mmHg (95% CI -9.34 to 0.02, p=0.01) and mean arterial pressure by -6.48 mmHg (95% CI -10.63 to -2.33, p=0.002) compared to controls. Additionally, RT significantly lowered fasting insulin levels by -12.52 mmol/L (95% CI -24.17 to -0.88, p=0.04) and HOMA-IR by -1.49 (95% CI -1.63 to -1.35, p＜0.00001). Improvements were more pronounced in participants with dietary control. Conclusion: Moderate-frequency RT effectively improves CRFs in overweight and obese adults, suggesting its potential as a beneficial intervention for this population. PROSPERO registration number: CRD42022343167.

The issue of antibiotic resistance represents a significant threat that extends beyond human health, encompassing animal welfare and the sustainability of the natural environment. The inappropriate use of antibiotics, poor sanitation and inadequate control measures, have contributed to the emergence of drug-resistant bacteria, which can spread at the human-animal-environment interface. The documented presence of antimicrobials in agriculture, veterinary medicine and human medicine has convinced all stakeholders of the need to contribute to the development of a "One Health" approach, which recognises the interrelationships between animals, humans and their environment and the need to adopt a common strategy encompassing these sectors to limit the spread of antimicrobial resistance (AMR). Although a number of countries have implemented integrated surveillance systems to monitor antibiotic use and antimicrobial resistance, available data suggest that the use of antibiotics in humans, animals and the environment is increasing worldwide. Consequently, the emergence of antibiotic-resistant pathogens is becoming a recurring concern. This review provides a comprehensive overview of the measures that are necessary to be taken and implemented in order to guarantee global health security.

Antimicrobial resistance (AMR) is a public health problem exacerbated by the overuse and misuse of antibiotics and an inadequate capacity of laboratories to conduct AMR surveillance. This study assessed the capacity of laboratories in seven faith-based hospitals to conduct bacteriology, AMR testing and surveillance in Zambia. This multi-facility, cross-sectional exploratory study was conducted from February 2024 to April 2024. We collected and analysed data using the self-scoring Laboratory Assessment of Antibiotic Resistance Testing Capacity (LAARC) tool. This study found an overall score of 39%, indicating a low capacity of laboratories to conduct AMR surveillance. The highest capacity score was 47%, while the lowest was 25%. Only one hospital had full capacity (100%) to utilise a Laboratory Information System (LIS). Three hospitals had good capacity to perform data management with scores of 83%, 85%, and 95%. Only one hospital had full capacity (100%) to process specimens, and only one hospital had good safety requirements for a microbiology laboratory, with a score of 89%. This study demonstrates that all the assessed hospitals have a low capacity to conduct AMR surveillance. Therefore, there is an urgent need to strengthen the microbiology capacity of laboratories to enhance surveillance in faith-based hospitals in Zambia.

To elucidate the function of the cold resistance regulatory gene FmNAC1 from Fraxinus mandshurica, this study identified the role that the overexpression of the FmNAC1 gene plays in tobacco growth and cold stress regulation. The cloned FmNAC1 gene from F. mandshurica is 891 bp in length and encodes 296 amino acids. Our subcellular localization analysis confirmed that FmNAC1 is primarily located in the nucleus and functions as a transcription factor. FmNAC1 is responsive to cold and NaCl stress, as well as to the induction of IAA, GA, and ABA hormone signals. To further elucidate its function in cold resistance, four transgenic tobacco lines of FmNAC1 overexpression（FmNAC1-OE）were generated through tissue culture after the agrobacterium-mediated transformation of wild-type (WT) tobacco. These FmNAC1-OE plants exhibited accelerated growth after transplantation. When exposed to low-temperature conditions at -5°C for 24 hours, the rates of wilting and yellowing of the FmNAC1-OE plants were significantly lower than those of the WT tobacco plants. Additionally, the membrane integrity, osmotic regulation, and reactive oxygen species (ROS)-scavenging abilities of the FmNAC1-OE tobacco lines were better than those of the WT plants, indicating the potential of the FmNAC1 gene to improve plant cold resistance. The gene expression results further revealed that the FmNAC1 transcription factor exhibits regulatory interactions with growth-related genes such as IAA and AUX1; cold resistance-related genes such as ICE, DREB, and CBF1; and genes involved in the clearance of reactive oxygen species (ROS), such as CAT and SOD. All of this evidence shows that the FmNAC1 transcription factor from F. mandshurica plays a key role in contributing to the enhancement of growth, cold resistance, and ROS clearance in transgenic tobacco plants.

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.

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.

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.

Aim: To investigate how much aerobic and resisted physical exercise affects the behavior of AST and ALT proteins in the NAFLD spectrum. Background: Non-alcoholic fatty liver disease (NAFLD) is a pathology resulting from the excessive accumulation of triglycerides in the liver. The pathophysiology of the disease comes from several mechanisms, among them, metabolic, environmental, and genetic. The measurement of liver enzymes, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) are essential to perform a differential diagnosis of NAFLD with other pathologies that affect the liver. The non-pharmacological treatment of NAFLD is based on aerobic and resisted physical exercise, and one of its aims is to reduce the inflammatory markers AST and ALT. Materials and Methods: Systematic review carried out in PubMed, Scopus, Embase, and Cochrane databases. Clinical trials that evaluated the effect of physical exercise on NAFLD on AST and ALT enzymes were included. Results: A total of 24 clinical trials met the inclusion criteria, with a sample size of 1141 participants, aged 20-82 years. The study protocol varied between aerobic exercise and resistance exercise with a weekly frequency between 2-6 times a week, a duration of 20-90 minutes for aerobics, and an intensity between 50-80% of peak VO2 and/or maximum HR for the resisted. Of the 24 studies included, only five showed improvements in both enzymes in the intervention group. Conclusion: Physical exercise cannot make significant changes in the behavior of AST and ALT liver parameters.

Carbapenems are considered for treating Klebsiella pneumoniae and other Enterobacteriaceae infections, especially if they are not susceptible to other generally prescribed antibiotics, i.e., if they show resistance. In such cases, antibiotic activity decreases, and most patients succumb to the infection. A better understanding of the disease pattern and resistance mechanisms could be gained by magnifying the genes that confer resistance to antibiotics. Therefore, studying the genes that confer resistance to carbapenems and any other antibiotics for that matter is indispensable for coming up with improved treatment options. This study included the analyses of co-resistance patterns between resistance genes-between drug classes and within the carbapenem-resistant genes, genomic context analysis of highly expressed carbapenem-resistant genes, and phylogenetic study of OXA-producing genes, plasmid incompatibility identification, and sequence type identification using MLST. The presence of ESBLs, MBLs, and SBLs across the downloaded genomes was studied. SHV-producing genes were found to co-occur with most of the resistant genes belonging to different drug classes. The plasmid incompatibility type IncFIB was found to be common among the highly expressed genes, and most of these genes were flanked by different families of insertion sequence (IS) elements. MLST study suggested that the presence of sequence types ST-11, ST-14, and ST-147 was common in the downloaded set of genomes.

White adipose tissue (WAT) represents an endocrinologically and immunologically active tissue that’s primary role is energy storage and homeostasis. Breast WAT is involved in the secretion of hormones and proinflammatory molecules that are associated with breast cancer development and progression. The role of adiposity and systemic inflammation in immune responses and resistance to anti-cancer treatment in breast cancer (BC) patients is still not clear. This review aims to evaluate the emerging evidence on the crosstalk between adiposity and the immune-tumour microenvironment in BC, its progression and treatment resistance. Adiposity, and by extension subclinical inflammation, are associated with metabolic dysfunction and changes in the immune-tumour microenvironment in BC. In oestrogen receptor positive (ER+) breast tumours, it is proposed that these changes are mediated via a paracrine interaction between macrophages and preadipocytes leading to elevated aromatase expression and secretion of pro-inflammatory cytokines and adipokines in the breast tissue in patients who are obese or overweight. In HER2+ breast tumours, WAT inflammation has been shown to be associated with resistance to trastuzumab mediated via MAPK or PI3K pathways. Furthermore, adipose tissue in patients with obesity is associated with upregulation of immune checkpoints on T-cells that is partially mediated via immunomodulatory effects of leptin and has been paradoxically associated with improved responses to immunotherapy in several cancers. In conclusion, evidence suggests that body composition and metabolic status are associated with patient outcomes. To optimise patient stratification and personalisation of treatment, prospective studies are required to evaluate the role of body composition and metabolic parameters in metabolic immune reprogramming with and without immunotherapy in patients with BC.

The plant immunity system is more and more revisited and new elements and roles are attributed to participate in the response to biotic stress. New terminology is also applied trying to identify different players in the whole scenario of immunity: Phytocytokines are one of those elements that are gaining more attention due the characteristics of processing and perception, and showing they are part of a big family of compounds that can amplify the immune response. This review aims to highlight the last findings about the role of phytocytokines in the whole immune response on biotic stress, including basal and adaptive immunity, and to expose the complexity in their action in plant perception and signaling events.

A set of aromatic copolyimides was obtained by reaction of 4,4′-(hexafluoroisopropylidene) diphthalic anhydride (6FDA), and mixtures of the diamines 1,4-bis(4-amino-2-trifluoromethylphenoxy)-2,5-di-tert-butylbenzene (CF3TBAPB) and 3,5-diamino benzoic acid (DABA). These polymers were characterized and compared with the homopolymer derived from 6FDA and CF3TBAPB. All copolyimides showed high molecular weight values and good mechanical properties. The presence of carboxylic groups in these copolymers allowed their cross-linking by reaction with 1,4-butanediol. The crosslinked polymer films were extensively characterized and it was observed that the degree of crosslinking was low in the copolyimides possessing a small number of carboxyl groups. The degradation temperature of these crosslinked copolyimides was lower than their corresponding non-crosslinked ones. Glass transition temperatures were higher than 260 oC, showing the non-crosslinked copolyimides the highest values. Young moduli of these crosslinked showed values higher than 1.9 GPa, and slightly lower elongation at break when compared with the precursor copolyimides. All copolyimides (precursor, and crosslinked ones) films could be tested as gas separation membranes. It was seen that CO2 permeability values were around 100 barrer, having better selectivity than that of the homopolymer. Moreover, the plasticization resistance of the crosslinked material having a large number of carboxylic groups was excellent.

We propose a model for bacterial Quorum Sensing based on an auxiliary electrostatic-like interaction originating from a fictitious electrical charge that represents bacteria activity. A cooperative mechanism for charge/activity exchange is introduced to implement chemotaxis and replication. The bacteria system is thus represented by means of a complex resistor network where link resistances take into account the allowed activity-flow among individuals. By explicit spatial stochastic simulations, we show that the model exhibits different quasi-realistic behaviors from colony formation to biofilm aggregation. The electrical signal associated with Quorum Sensing is analyzed in space and time and provides useful information about the colony dynamics. In particular, we analyze the transition between the planktonic and the colony phases as the intensity of Quorum Sensing is varied.

Due to nutritional benefits and perceived humane ways of treating the animals, the demand for antibiotic-free pastured poultry chicken has continued to be on a steady rise. However, despite non-usage of antibiotics in pastured poultry broiler production, antibiotic resistance (AR) is reported in zoonotic poultry pathogens. However, actors that drive multidrug resistance (MDR) in pastured poultry are not known. In this study, we used machine learning and deep learning approaches to predict farm management practices, and physicochemical properties of feces and soil that drive MDR in zoonotic poultry pathogens. Antibiotic use in agroecosystems is known to contribute to resistance. Evaluation of the development of resistance in environments that are free of antibiotics such as the all-natural antibiotic-free, pastured poultry production systems described here is critical to understand the background AR. We analyzed 1,635 preharvest (feces and soil) samples collected from forty-two pastured poultry flocks and eleven farms in the Southeastern United States. CDC National Antimicrobial Resistance Monitoring System guidelines were used to determine antimicrobial/multidrug resistance profiles of Salmonella, Listeria and Campylobacter. A combination of two traditional machine learning (RandomForest and XGBoost) and three deep learning (Multi-layer Perceptron, Generative Adversarial Network, and Auto-Encoder) approaches, identified critical farm/environmental variables that drive multidrug resistance in poultry pathogens, in broiler production systems that represents background resistance. This study enumerates management practices that contribute to AR and recommendations to potentially mitigate multidrug resistance and prevalence of Salmonella and Listeria in pastured poultry.

Bacterial vaginosis (BV), the most common cause of vaginal discharge, is characterized by a shift in the vaginal microbiota from lactobacillus dominance to a diverse array of facultative and strict anaerobic bacteria which form a multi-species biofilm on vaginal epithelial cells. The rate of recurrence after therapy is high, often >60%. While the BV biofilm itself likely contributes to recurrent and/or refractory disease after treatment by reducing antimicrobial penetration, antimicrobial resistance in BV-associated bacteria including those, both within the biofilm and the vaginal canal, may be the result of independent, unrelated bacterial properties which are discussed in this paper. Our current recommendations for the treatment of refractory and recurrent BV are also provided.

In two sequential replicates (n=90 and n=96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p&lt;0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin. A similar observed effect was not statistically significant (P &gt; 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. E. faecium isolates were whole-genome sequenced, which yielded sequence types (ST), resistance genes and phylogeny. Samples of the DFM were sequenced and found to contain E. faecium ST296, which was not present on Day 0 of either replicate. This DFM sequence type was found in fecal samples after Day 0, the majority of which were isolated from cattle in one of the DFM-fed pens. Increased prevalence of ST296 occurred with a concomitant decrease in ST240; of importance, the latter typically harbored both ermB and tet(M) genes.

The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.

The prevalence of multidrug resistant bacterial diseases is a major global health risk. Multidrug resistant bacterial diseases are prevalent, and the need for novel methods of treatment is essential to the preservation of public health. Annually foodborne pathogens cause 1.35 million infections and 26,500 hospitalizations in the United States alone. Foodborne pathogens such as Salmonella spp. are a major threat to public health. Bacteriophages offer a unique method for the treatment of these multidrug resistant bacteria. We studied the infection dynamics of a potential mono-phage therapy of Salmonella typhimurium under various pathophysiological conditions. Furthermore, we determined the resistance dynamics of Salmonella typhimurium against P22 phage treatment. We also determined synergy with antibiotics such as ampicillin and kanamycin. This research helps to further define and show the versatility of bacteriophages as potential novel treatment methods.

Ultrafast chip nanocalorimetry opens up remarkable possibilities in materials science by allowing samples to be cooled and heated at extremely high rates. Due to heat transfer limitations, controlled ultrafast cooling and heating can only be achieved for tiny samples in calorimeters with a micron-thick membrane. Even if ultrafast heating can be controlled under quasi-adiabatic conditions, ultrafast controlled cooling can be performed if the calorimetric cell is located in a heat-conducting gas. It was found that the maximum possible cooling rate increases as 1/r0 with decreasing radius r0 of the hot zone of the membrane. The possibility of increasing the maximum cooling rate with decreasing r0 was successfully implemented in many experiments. In this regard, it is interesting to answer the question: what is the maximum possible cooling rate in such experiments if r0 tends to zero? Indeed, on submicron scales, the mean free path of gas molecules lmfp becomes comparable to r0, and the temperature jump that exists at the membrane/gas interface becomes significant. Considering the limitation associated with thermal resistance at the membrane/gas interface and considering the transfer of heat through the membrane, we show that the controlled cooling rate can reach billions of K/s, up to 1010 K/s.

The outbreak of yellow fever transmitted by Aedes aegypti has been of major concern in Nigeria, this mosquito also transmits several other arboviruses globally. The control of many of the Aedes aegypti borne diseases relies heavily on the use of insecticides. Therefore, constant monitoring of insecticide resistance status and associated mechanisms in crucial within the local population. Here, we determined the resistance profile of adult Aedes aegypti from Ikorodu Local Government Area of Lagos State, Nigeria to different classes of insecticides using WHO procedures. The presence of kdr mutations F1534C, S989P and V1016G were also determined among resistant populations using molecular methods. High level of resistance to DDT and pyrethroid was rec-orded in Aedes aegypti in this study, though possible resistance to deltamethrin was reported in one of the locations. Resistance to bendiocarb was recorded in Majidun community while Aedes aegypti in both locations were susceptible to malathion. The presence of F1534C mutation associated with resistance in Aedes aegypti was detected for the first time in Nigeria, and the presence of S989P mutation was detected singly and in co-occurrence with F1534C for the first time in Africa. The role of these mutations in resistance phenotype expressed in Aedes aegypti in this study area need to established.

With the rapid population growth, there is an urgent need for innovative crop improvement approaches to meet the increasing demand for food. Classical crop improvement approaches involve, however, a backbreaking process that cannot equipoise with increasing crop demand. RNA based approaches i.e. RNAi-mediated gene regulation and site-specific nuclease based CRISPR/Cas9 system for gene editing has made advances in the efficient targeted modification in many crops for the higher yield and resistance to diseases and different stresses. In functional genomics, RNA interference (RNAi) is a propitious gene regulatory approach that plays a significant role in crop improvement by permitting down-regulation of gene expression by small molecules of interfering RNA without affecting the expression of other genes. Gene editing technologies viz. clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (CRISPR/Cas) have appeared prominently as a powerful tool for precise targeted modification of nearly all crops genome sequence to generate variation and accelerate breeding efforts. In this regard, the review highlights the diverse roles and applications of RNAi and CRISPR/Cas9 system as powerful technologies to improve agronomically important plants to enhance crop yields and increase tolerance to environmental stress (biotic or abiotic). Ultimately, these technologies can prove to be important in view of global food security and sustainable agriculture.

Background: Pneumococcal carriage surveillance study took place in urban and rural areas for Jordanian children in the period 2015-2019. Objectives: Determine urban and rural differences in pneumococcal carriage rate, resistance, and serotypes from healthy Jordanian children of Amman (urban) and eastern Madaba (rural). Methods: Nasopharyngeal swabs (NP) were taken from 682 children aged 1 to 163 months. Pneumococcal identification, serotyping and resistance were done according to standard method. Results: Number of cases tested for Amman 267 and for eastern Madaba 415. Carriage rate for eastern Madaba was 39.5% and for Amman 31.1%. Predominant serotypes for eastern Madaba and Amman were 19F (21.3%; 15.7%), 23F (12.2%; 9.6%), 14 (6.7%; 2.4%), 19A (4.9%; 2.4%), 6A (5.5%; 3.6%). Resistance rates for eastern Madaba and Amman were: penicillin (95.8%; 81.9%), clarithromycin (68.9%; 59.0%), clindamycin (40.8%; 31.3%), and trimethoprim-sulfamethoxazole (73.2%; 61.4%). Coverage of PCV7, PCV13, and the future PCV20 for Amman were 42.2%, 48.2%, and 60.2%; and for eastern Madaba were 50.0%, 62.2%, and 73.2%, respectively. In Amman 25.8% have received 1-3 PCV7 injections compared to 1.9% in eastern Madaba. Conclusions: There was significant differences in carriage, resistance and coverage in both regions. The potential inclusion of PCV vaccination program for rural areas is essential.

Salmonella remains one of the notable food-borne bacterial pathogens. It is associated with poultry and poultry products including eggs. This study investigated Salmonella distribution in eggshell and content, their antimicrobial resistance pattern, and the possible risk factors driving contamination in Ogun State, Nigeria. A total of 500 eggs (5 eggs pooled into one sample) were collected and culturally examined for the presence of Salmonella serovars. Isolates were further characterized biochemically using Microbact 20E (Oxoid) and Antimicrobial susceptibility determined by the Kirby-Bauer disk diffusion method. A total of 14 Salmonella isolates spread across 10 serovars were recovered from the 100 pooled egg samples; 10 (10%) from the market and 4 (4%) farms, 13(13%) eggshell, and 1(1%) egg content. All tested serovars were susceptible to ampicillin, chloramphenicol, florfenicol, and kanamycin. Resistance was mostly observed in sulfamethoxazole 8 (80%), followed by ciprofloxacin 5 (50%) and tetracycline 3 (30%). Sales of eggs in the market appears to be a strong factor encouraging contamination in addition to poor biosecurity and unhygienic handling of eggs on the farm.

Campylobacter is one of the major foodborne pathogens of concern in its growing trend of antimicrobial resistance. C. jejuni and C. coli are the major causative agents, with C. jejuni contributing to most of the cases in approximately 90% in the world. Infection is transmitted to humans due to consumption of contaminated food and water. Campylobacteriosis caused by C. jejuni is commonly presented with severe diarrhoea, abdominal pain, fever, headache, nausea, and vomiting with some extreme cases resulting in Guillain–Barré syndrome (GBS) and acute flaccid paralysis. Symptoms are severe in cases of children below 5 years, elderly and individuals who are immunocompromised. The infection is usually sporadic, and self-limiting and thus does not require antibiotics for treatment. Still, the antimicrobial resistance in Campylobacter is a major concern because of the transmission of resistance from animal sources to humans. This review highlights the recent epidemiology, geographical impact, resistance mechanisms, spread of Campylobacter spp. and the strategies to control the transmission of Campylobacter from veterinary sources and its antimicrobial resistance.

The aim of this study is to investigate the effect of two antiglaucoma procedures, namely trabeculectomy and Ex-PRESS mini-shunt insertion on the biomechanical properties of the cornea. This is a prospective study. Thirty patients (30 eyes) were included in the study. Nineteen eyes had an Ex-PRESS shunt inserted (Group 1) and 11 had trabeculectomy (Group 2). The examination time points for both groups were 1 to 3 weeks preoperatively and at month 1, 6 and 12 postoperatively. Corneal biomechanical properties [corneal hysteresis (CH) corneal resistance factor (CRF)] were measured with the Ocular Response Analyzer. In group 1, CH was significantly increased at 6 and 12 months compared to baseline values. Corneal hysteresis was also higher at 1 month postoperatively but this increase did not reach statistical significance. In group 2, the CH was significantly increased at all time points compared to the preoperative values. CRF decreased at all time points postoperatively compared to the preoperative values in both groups. The difference (preoperative values to postoperative values at all time points) of the CH and CRF between the two groups was also compared and no significant differences were detected between the two surgical techniques. Trabeculectomy and the EX-PRESS mini-shunt insertion alter significantly the corneal biomechanical properties as a result of the surgical trauma and the presence of the shunt in the corneal periphery. When compared between them they affect the corneal biomechanical properties in a similar way.

Increased levels of insecticide resistance in major malaria vectors such as Anopheles funestus threaten the effectiveness of insecticide-based control programmes. Understanding the landscape features impacting the spread of resistance makers is necessary to design suitable resistance management strategies. Here we examined the influence of the highest mountain in West Africa (Mount Cameroon; 4,100 meters elevation) on the spread of metabolic and target-site resistance alleles in An. funestus populations. Vector composition varied across the four localities surveyed along the altitudinal cline with major vectors exhibiting high parity rate (80.5%). Plasmodium infection rates ranged from 0.79% (An. melas) to 4.67% (An. funestus). High frequencies of GSTe2R (67% - 81%) and RdlR (49% - 90%) resistance alleles were observed in An. funestus throughout the study area, with GSTe2R frequency increasing with altitude whereas the opposite is observed for RdlR. Patterns of genetic diversity and population structure analyses revealed high levels of polymorphisms with 12 and 16 haplotypes respectively for GSTe2 and Rdl. However, the reduced diversity patterns of resistance allele carriers revealed signatures of positive selection on the two genes across the study area irrespective of the altitude. Despite slight variations associated with the altitude, the spread of resistance alleles suggest that control strategies could be implemented against malaria vectors across mountainous landscapes.

Multidrug resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach; we have modified the antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-ester-PPh3), to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3 and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (MRSA) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with an MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivates induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria, through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.

Nuclear pollution is an urgent environmental issue as a consequence of rapid industrialization and nuclear accidents in the past. Remediation of nuclear polluted sites using microbial vital activity (bioremediation) is a promising approach to recover contaminated areas in an environmentally friendly and cost-saving way. At the same time, the number of known bacterial and archaeal species able to withstand extremely high doses of ionizing radiation is steadily growing every year, together with growing knowledge about mechanisms of radioresistance. This opens up new opportunities for developing new biotechnological solutions. However, these data are often not systemized and it can be difficult to access. Here, we present the Determinants of Radioresistance Database, or DetR DB (http://extremebiolab.com/detr-db/), gathering a comprehensive catalog of radioresistant microbes and their molecular and genetic determinants of enhanced ionizing radiation tolerance. The database provides search tools including taxonomy, common gene name, and BLAST. DetR DB will be a useful tool for research community by facilitating the extraction of the necessary information to help further analysis of radiation-resistant mechanisms.

This review was carried out to identify different beta-lactamase resistance genes reported in published literature from Nigeria and to determine the proportion estimates of the important beta-lactamase resistance genes in Nigeria. Sixty-three (63) articles were included in this review based on the eligibility criteria. All the beta-lactamases reported were detected from the Gram-negative bacteria, most especially from Enterobacteriaceae (n=53). Thirty-six different beta-lactamase genes have been reported from Nigeria. These genes belong to the narrow-spectrum, AmpC, extended-spectrum, and carbapenemase beta-lactamase resistance genes. Eight (8) genes (bla_DHA, bla_CTXM-1, bla_CTXM-14, bla_GES-1, bla_VEB-1, bla_OXA-1, bla_OXA-2, and bla_TEM-1) were shared between animals and humans, 5 genes (bla_SHV-1, bla_SHV-2, bla_SHV-11, bla_SHV-12, and bla_NDM-1) were common to both humans and environment while none of the genes was unique to both animals and environment. Four genes including bla_CMY, bla_TEM-1, bla_AmpC, and internationally pandemic bla_CTXM-15 gene were unique to animals, humans, and the environment. No carbapenemase gene was reported from animals yet. The pooled proportion estimate of ESBL genes in Nigeria was 31% (95% CI: 26-36%, P<0.0001), while the estimate of bla_CTXM-15 gene in Nigeria was 46% (95% CI: 36-57%, P<0.0001). The proportion estimate of AmpC genes was 32% (95% CI: 11-52%, P<0.001), while the estimate for carbapenemases was 8% (95% CI: 5-12%, P<0.001). This study has provided information on the beta-lactamases distribution in Nigeria. This is necessary for a better understanding of molecular epidemiology of clinically important beta-lactamases especially the extended-spectrum beta-lactamases and carbapenemases in Nigeria.

The potential of A. baumannii for acquired resistance to last resort antibiotics (colistin and tigecycline) during treatment has important clinical implications, especially when dealing with patients failing to improve despite treatment with an active antimicrobial. However, the relevant literature remains scattered. Therefore, a systematic search was conducted in PubMed and Scopus. Several studies reported emergence of resistance to colistin or tigecycline during treatment, in most cases (86%) resulting in persistent or recurrent infections, especially in cases of emergent resistance without fitness cost. Lipopolysaccharide modification in the case of colistin and overexpression of efflux pumps in the case of tigecycline were the main mechanisms of resistance. Emergent colistin resistance is often associated with fitness cost resulting in re-emergence of the fitter and more virulent colistin susceptible strain after cessation of antibiotic pressure. Prospective studies are needed to determine the frequency of emergent resistance during treatment and its impact on patient outcomes.

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, β-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the β-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.

There is an increasing interest in applying environmentally-friendly materials in wood protection technology. This include the use of less toxic active ingredients, as well as better fixation. This study investigates the formulation based on the combination of copper and Saqez resin on the physical and biological resistance properties of poplar wood. Samples were treated by either copper-ethanolamine (Cu/MEA) and/or Saqez resin at various treatment levels. A vacuum pressure procedure was applied. The retention, weight percent gain, water absorption, volumetric swelling, and decay resistance of the samples were then determined. The highest retention and weight percent gain were obtained at the samples treated with the combination of copper-based system and Saqez resin. Additionally, the combination of the copper and Saqez improved the physical properties and decay-resistance against white-rot fungus Trametes versicolor.

The novel coronavirus, COVID-19 is now officially declared as a pandemic by the World Health Organization (WHO), and most parts of the world are taking drastic measures to restrict human movements to contain the infection. Like millions of others around the world, I am wondering, is there anything that could be done, other than keeping high personal hygiene, and be vigilant of symptoms, to reduce the chances of infection, or at least to reduce the burden of the disease. So far, the National and International health agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the WHO have provided clear guidelines for both preventive and treatment suggestions. In this opinion-based article, I want to discuss, why keeping the adequate micronutrient balance might enhance the host response and be protective of viral infections. A detailed in-depth discussion of various micronutrients is not the purpose of this article, I will mostly emphasize on the role of zinc in viral infection.

Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyze and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines by 1-million array-CGH and qRT-PCR methodologies. RNA-sequencing, functional transfection assays and gene-pathway activity analysis were used to identify genes with a potential role in the development of this malignancy. Results were further explored in 55 lung and ovarian primary tumors and control samples and in two extensive in silico databases. Long-term cell exposure to platinum induces the frequent deletion of ITF2 gene. Its expression re-sensitizes tumor cells to platinum and recovers the levels of Wnt/β-catenin transcriptional activity. ITF2 expression was also frequently downregulated in epithelial tumors, predicting a worse overall survival. We also identified an inverse correlation between ITF2 and HOXD9 expression, revealing that NSCLC patients with lower expression of HOXD9 have a better overall survival rate. We define the implication of ITF2 as a molecular mechanism behind the development of cisplatin resistance probably through the activation of the Wnt-signaling pathway. This data highlights the possible role of ITF2 and HOXD9 as novel therapeutic targets for platinum resistant tumors.

In this review, we highlight new findings that have deepened our understanding of the mechanisms of leukemogenesis, therapy and resistance in APL. PML-RARa sets the cellular landscape of Acute promyelocytic leukemia (APL) by repressing transcription of RARa target genes and disrupting PML-NBs. RAR receptors control the homeostasis of tissue growth, modeling and regeneration, PML NBs are involved in self-renewal of normal and cancer stem cells, DNA damage response, senescence and stress response. Additional somatic mutations in APL mainly involve FLT3, WT1, NRAS, KRAS, ARID1B and ARID1A genes. Treatment outcomes in patients with newly diagnosed APL improved dramatically since the advent of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). ATRA activates the transcription of blocked genes and degrades PML-RARα, while ATO degrades PML-RARa by promoting apoptosis and has a pro-oxidant effect. Resistance to ATRA and ATO may derive from mutations in the RARa ligand binding domain (LBD) and in the PML-B2 domain of PML-RARa, but such mutations cannot explain the majority of resistances experienced in the clinic, globally accounting for 5-10% of cases. Several studies are ongoing to unravel clonal evolution and resistance, suggesting the therapeutic potential of new retinoid molecules and combinatorial treatments of ATRA or ATO with different drugs acting through alternative mechanisms of action, which may lead to synergistic effects on growth control or induction of apoptosis in APL cells.

The carbapenemase OXA-244 is a derivate of OXA-48, and its detection is very difficult in laboratories. Here we report the identification and genomic analysis of an Escherichia coli isolate (28Eco12) harbouring the bla_OXA-244 gene identified in Colombia, South America. The 28Eco12 isolate was identified during a retrospective study and it was recovered from a patient treated in Colombia. The complete nucleotide sequence was established using the PacBio platform. A comparative genomics analysis with other bla_OXA-244–harbouring Escherichia coli strains was performed. The 28Eco12 isolate belonged to sequence type (ST) 38 and its genome was composed of two molecules, a chromosome of 5,343,367 bp and a plasmid of 92,027 bp, which belonged to the incompatibility group IncY and did not harbour resistance genes. The bla_OXA-244 gene was chromosomally-encoded and mobilized by an ISR1-related Tn6237 composite transposon. Notably, this transposon was inserted and located within a new genomic island. For our knowledge this is the first report of a bla_OXA-244–harbouring Escherichia coli isolate in American continent.Our results suggest that the introduction of the OXA-244-producing E. coli isolate was through clonal expansion of the ST38 pandemic clone. Other isolates producing OXA-244 could be circulating silently on the American continent.

With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance, we are seeing an increased intersection of genomics, microbiology, and clinical epidemiology. Clear nomenclature for AMR gene families and pathogens is critical for communication. For CARD release version 3.0.3 (July 2019), we updated the entire CARD database to reflect the latest pathogen names. In total, we detected 48 name changes or updates, some of which reflect major changes in familiar names.

The basic pattern of MHC variation in fish, with MHC class I versus class II, and polymorphic classical versus nonpolymorphic nonclassical, is similar in fish and mammals. Nevertheless, in many or all teleost fishes, important differences with mammalian or human MHC were observed: (1) The allelic/haplotype diversification levels of classical MHC class I genes tend to be much higher than in mammals; (2) Teleost fish classical MHC class I and class II loci are not linked. The present article summarizes previous studies that performed quantitative trait loci (QTL) analysis for mapping differences in teleost fish disease resistance, and discusses them from MHC point of view. Overall, those studies suggest the possible importance of genomic regions including classical MHC class II and nonclassical MHC class I genes, whereas similar observations were not made for the genomic regions with the highly diversified classical MHC class I alleles. The present study is a review and discussion of the fish MHC situation.

Background: Infections caused by E. coli cause considerable disease burden and range from frequently occurring and relatively innocent urinary tract infection (UTI) to severe bloodstream infection (BSI). The incidence of infections caused by ESBL-producing E. coli (ESBL-PEc) is increasing, justifying surveillance and development of preventive strategies in several domains. Faecal carriage is universal and believed to be the most important reservoir for E. coli from which infections can originate. It is currently unknown to what extent Dutch E. coli carriage strains in the community reflect isolates causing disease. In this study, we will perform comparative genomics to infer the population structures of human-derived ESBL-PEc from community- and hospital-acquired infections and from community-based faecal carriage samples in the Netherlands. Furthermore, we will describe the molecular epidemiology of E. coli isolates causing invasive disease (BSI). Methods: This study uses four different microbiological data sources: 1) ESBL-PEc from patients with community-acquired UTI tested in primary care between May and November 2017, 2) ESBL-PEc from urine cultures obtained from patients hospitalized between January 2014 and December 2016, 3) E. coli from blood cultures obtained from patients hospitalized between January 2014 and December 2016, and 4) ESBL-PEc from faecal samples collected in a national population- prevalence study performed between January 2014 and January 2017. Clinical epidemiological data was collected from all patients and all isolates were subjected to whole genome sequencing. Discussion: The EPIGENEC study (EPIdemiology and GENetics of E. coli) will describe the molecular epidemiology of E. coli BSI and assess the genomic population structure of ESBL-PEc strains from community-acquired and nosocomial infections, and of ESBL-PEc reflecting community-based faecal carriage. Information from these studies may assist in optimizing surveillance strategies and determining targets and potential impact of future new preventive measures.

Insulin resistance is a prominent pathophysiologic syndrome in a plethora of metabolic disorders including obesity, prediabetes, type 2 Diabetes Mellitus (Ten et al., 2007), impaired glucose tolerance, dyslipidemia, polycystic ovary syndrome and hypercoagulability (Smith & LeRoith, 2004). It is strongly associated with obstructive sleep apnea, hypoventilation syndrome, pancreatitis, nonalcoholic fatty liver disease, steatohepatitis, cirrhosis, gall bladder disease, multiple cancers (breasts, uterus, cervix prostate, kidney, colon, esophagus, pancreas and liver), stroke, cataracts, coronary heart disease, and hypertension. It is also associated with causation of abnormal menses, infertility, polycystic ovary syndrome, osteoarthritis, phlebitis and other venous diseases. Insulin resistance is thought to be caused by intrinsic and extrinsic factors that contribute to its development. Once present, insulin resistance affects the metabolism, behavior, physical appearance and has lasting effects. This paper will review the latest evidence in development of insulin resistance, its pathogenesis and manifestation and its relation to other conditions. The final aim is to raise awareness of its role on diet, metabolic, genetics and microbiome.

HER2/neu positive breast tumors predict a high mortality and comprise 25-30% of breast cancer. We have shown that Flavokawain A (FKA) preferentially reduces the viabilities of HER2 overexpressing breast cancer cell lines (i.e. SKBR3 and MCF7/HER2) versus those with less HER2 expression (i.e. MCF7 and MDA-MB-468). FKA at cytotoxic concentrations to breast cancer cell lines also has minimal effect on the growth of non-malignant breast epithelial MCF10 cells. FKA induces G2M arrest in cell cycle progression of HER2 overexpressing breast cancer cell lines through inhibition of Cdc2 and Cdc25C phosphorylation and down-regulation of Myt1 and Wee1expression leading to increased Cdc2 kinase activities. In addition, FKA induces apoptosis in SKBR3 cells by increasing the protein expression of Bim and BAX and decreasing expression of Bcl₂, Bcl_x/L , XIAP and survivin. FKA also down-regulates the protein expression of HER-2 and inhibits AKT phosphorylation. Herceptin plus FKA treatment leads to enhanced growth inhibitory effect on HER-2 overexpressing breast cancer cell lines through down-regulation of Myt1, Wee1, Skp2, Survivin and XIAP. Our results suggest the promise of FKA as a novel apoptosis inducer and G2 checkpoint abrogating agent in combination with Herceptin for treatment of HER2 overexpressing breast cancer.

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

In many parts of the Asia, particularly in the arid regions of the middle east the date palm i.e. Phoneix dactylifera L. is considered a significant plant both culturally and economically. Over the past decade numerous biotechnological tools have been applied to revolutionize the date palm research and its cultivation process. In this comprehensive review ,we provided the in depth overview of the cutting edge developments in the date palm biotechnology, mentioning the important areas such as genomics, genetic engineering, in vitro propagation, omics technologies, and the integration of the artificial intelligence and machine learning (AI-ML).Due to these advancements ,in the date palm production how the date palm production lead the production of superior date palm cultivars with the improved yield ,fruit quality and resilience to biotic and abiotic stresses. Also it explores the application of the biotech tools in the enhancing pest and disease management strategies, increasing date palm productivity and developing the date palm based bio-factories for the production of high value compounds. This review highlights the current challenges faced by the date palm industries ,including the limited water resources ,genetic erosion , pests and disease and the need for improved postharvest handling and processing. It examines how these tools coupled with AI-based approaches can be leveraged to address these challenges and ensure the long term sustainability of date palm cultivation.

The challenge posed by multi-drug resistance (MDR) of pathogenic organisms, spectacularly manifested in the 6 “ESKAPE” bacterium (two Gram-positive, four Gram-negative) species, should invoke new comprehensive strategies, and needs cooperation of scientists with medical, veterinary and natural science background. This review is aimed at informing newcomers, coming from the field of biology and genetics, about problems related to rapidly emerging, new multi-drug resistant, pathogenic, bacteria. Unlike persistence, the antibiotic resistance is inherited. A functioning “resistance gene” makes a susceptible organism resistant to a given antibiotic, encoding for polypeptides capable of acting either as decomposing enzymes, or acting as trans-membrane pumps, or membrane structure components capable of modifying the permeability implementing a «by pass» mechanism enabling the antibiotic molecule to reach its cellular target(s). A functioning “sensitivity gene” encode for a polypeptide, capable (directly or indirectly) of transferring toxic molecules into target cells, or of metabolizing non-transferable to transferable, or non-toxic molecules to toxic derivatives. A gene of a normal function could act as a “sensitivity” gene in the presence of antibiotics of chemical structures similar to the natural substrate of the gene product, (enzyme or binding/ trans-membrane protein). The Agrocin 84 story is a good example. Multi-drug resistance is a phenotypic consequence of the sequential accumulation of mutations, and/or up-take of plasmids or genomic islands carrying resistance genes from the environment via horizontal gene transfer, mediated by conjugative plasmid or bacteriophage carrying mobile genetic elements. Both multi-drug resistance and collateral sensitivity are evolutionary products. Some revealed evolutionary process and their Lamarckian and Darwinian interpretations are discussed. Toolkits of comparative full-genome sequencing, genomics, experimental evolution and population genetics may provide perspectives for overcoming the invincibility of multi-drug panresistance. The status of some recently emerging pathogenic bacterium species with zoonic features and of veterinary background is also discussed.

Sources of resistance to powdery mildew in wild barley (Hordeum vulgare subsp. spontaneum) collected in Jordan, Lebanon, and Libya Jerzy H. Czembor 1, *, Elżbieta Czembor 1 1 Plant Breeding and Acclimatization Institute – National Research Institute (IHAR-PIB), Radzikow, 05-870 Błonie, Poland; e.czembor@ihar.edu.pl (E.C.) *Correspondence: j.h.czembor@ihar.edu.pl) Abstract Barley powdery mildew (BPM) is caused by the pathogen Blumeria graminis f.sp. hordei (Bgh). It is an economically important disease and plant pathologists are looking for new sources of resistance to BPM. Barley genetic resources present in gene banks are often a rich source of disease resistance to be used by breeders. These new sources of resistance to BPM are often used in combination (pyramiding) with those that are already used in modern cultivars. Barley accessions, including the wild subspecies Hordeum vulgare subsp. spontaneum (Hvs), are stored in many gene banks and often are a valuable source of economically important characteristics. This source of biodiversity should be more efficiently used to improve barley in the process of plant breeding. However, their proper characterization and availability are urgently needed. The resistance to BPM in 81 accessions of wild barley (Hvs) collected in Jordan (47), Lebanon (23), and Libya (11) was investigated. The seed samples of these accessions were obtained from the ICARDA gene bank and collected in 10 expeditions from 1981 to 1995. Twenty European differential isolates of BPM were used to select accessions with efficient resistance. Thirty-one resistant single plant lines were selected from 15 accessions from Jordan and Libya based on tests performed with the most avirulent isolate of Bgh available. These resistant single plant lines were tested for the presence of specific resistance genes using a differential set of Bgh isolates. After analysis of obtained results, it was concluded that all tested 31 single plant lines of wild barley have genes for resistance that are not represented in the Pallas isolines differential s. Twenty-six lines of Hvs selected from accessions originated in Jordan and Libya showed resistance reaction to all isolates used. Identified new sources of effective resistance to BPM in single plant lines of Hvs will be further tested and used in barley pre-breeding programs. Keywords: Blumeria graminis; resistance genes; resistance; germplasm; gene bank;

Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.

Chronic mountain sickness (CMS) poses a significant health risk to individuals who rapidly ascend to high altitudes, potentially endangering their lives. Inorganic nanoparticles offer an effective means of transporting and delivering drugs, protecting nucleic acids from nuclease degradation, and mediating the expression of target genes in specific cells. These nanoparticles are almost non-toxic, easy to prepare and store, possess a large surface area, exhibit good biocompatibility and degradability, and maintain good stability. They can be utilized in the treatment of CMS to enhance the therapeutic efficacy of drugs. This paper provides an overview of the impact of inorganic nanomaterials on CMS, discussing their roles as nanocarriers and their potential in CMS treatment. It aims to present novel therapeutic strategies for the clinical management of CMS and summarizes the relevant pathways through which nanomaterials contribute to plateau disease treatment, providing a theoretical foundation for future clinical research.

Introduction: Pharmaceutical tablets are solid forms administrated orally and they constitute 80% of the market because of its best stability and ease of large-scale production, adherence and treatment. The Brazilian Legislation establishes that for a drug to be registered as a similar or generic drug is necessary to verify the pharmaceutical equivalence in relation to the reference drug, indicated by ANVISA, through quality control tests, ensuring that the drug is approved with satisfactory quality. Objective: to evaluate the reference, generic and similar glibenclamide tablets through quality control tests, comparing the results with each other and relate clinical impacts on the patient in the face of changes in the quality control of medicines. Methodology: tests of average weight, friability and disintegration were done, according to the Brazilian Pharmacopoeia VI Edition, in uncoated tablets of Glibenclamide 5mg Reference (Daonil), Generic (Glibenclamide) and Similar (Glionil), and the results obtained were compared with the that advocates the scientific literature. Results: Data referring to the average weight: Reference 0.1591g, Generic 0.1002g and Similar 0.0996g; For friability: Reference value 0.54%, Generic value 0.49% and Similar value 0.28%. The disintegration tests showed the following times: Reference 35 seconds, Generic 29 seconds and Similar 33 seconds. Conclusion: the tests to which the glibenclamide tablets were submitted showed results within the parameters established by the Brazilian Pharmacopoeia.

The authors propose a novel approach for a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while preserving animal life. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate-calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity, signs of neurological deficits (paresis, paralysis, etc.), as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.

Anticonvulsant drugs are widely used in the management of epilepsy and other neurological disorders. However, their concomitant use with other medications can lead to significant drug interactions, impacting both efficacy and safety. This article aims to provide a comprehensive overview of common anticonvulsant interactions with other frequently used drugs. It discusses the mechanisms of these interactions, their clinical implications, and strategies for managing them. The article also highlights the importance of monitoring and patient education in minimizing adverse outcomes.

Long COVID is a phenomenon in which individuals experience persistent symptoms after recovering from COVID-19. The symptoms are discovered to be unique for every individual and can affect multiple organs systems in the body. This study aims to identify effective natural remedies for long COVID by analyzing hub genes associated with the symptoms of the condition and evaluating the repurposed drugs catered and used for treating the symptoms of long COVID. The most common and prevalent symptoms of long COVID were identified; Fatigue, Shortness of Breath, Loss of Smell, Headache, Brain Fog, Chest Pain, Insomnia, Heart Palpitations, Dizziness, Joint Pain, Depression, Anxiety, Tinnitus, Loss of Appetite. Hub genes for each of the symptoms provided an insight on the key biological pathways of the symptom. Repurposed drugs identified, provided the template to identify the natural compounds with similar structure as a potential therapeutic drug. The natural compounds were retrieved using fingerprint search of the repurposed drugs from the NPASS Database. The findings of this study suggest several natural remedies for each symptom based on the molecular docking of the hub gene and natural compound using iGEMDOCK. The identified natural remedies may hold promise in treating long COVID, but further research is required to explore the efficacy and effectiveness of the proposed natural compounds. The results of the study pose important implications for the development of effective treatments for long COVID.

This review critically evaluates the role of Antibody-drug conjugates (ADCs) in the treatment of urothelial cancer, exploring their therapeutic potential and addressing the scientific and clinical challenges encountered in the development of these agents. It also discusses the recent approvals and clinical trials that are shaping the future of ADC therapy in this field. Through a detailed examination of the mechanism of action of ADCs, including the bystander effect, this paper aims to highlight both the successes and the limitations of these drugs in clinical settings. The main objective of this work is to provide a thorough overview of the current state of ADCs in urothelial cancer treatment, elucidating how these drugs can offer improved outcomes for patients. By discussing the broader implications of ADC technology and its integration into existing treatment paradigms, this review outlines the next steps in research and application necessary to overcome the existing challenges and harness the full potential of ADCs in cancer therapy.

Curcumin is a nutraceutical known to have numerous medicinal effects including anticancer activity. However, due to its poor water solubility and bioavailability, the therapeutic impact of curcumin against cancer, especially breast cancer, has been constrained. Encapsulating curcumin into chitosan nanoparticles (CHNPs) is an effective method to increase its bioavailability as well as antitumorigenic activity. In the present study, the effect of curcumin encapsulated CHNPs (Cur-CHNPs) on cell migration, targeted homing and tumour growth was examined using in vitro and in vivo breast cancer models. Cur-CHNPs possessed monodispersed nature with long term colloidal stability, and demonstrated significant inhibition of cell viability in vitro, which was potentiated by 5-fluorouracil (5-FU). Outcomes of the in vivo imaging studies confirmed effective tumour targeting and retention ability of Cur-CHNPs, thereby suppressing breast tumour growth in mice models. Overall, the results demonstrated that Cur-CHNPs, could be an effective candidate drug formulation for management of breast cancer.

Carbon nanodots (CNDs) have garnered significant attention as viable drug delivery vehicles in recent years, especially in the field of phytomedicine. Although there is much promise for therapeutic applications with phytomedicine, its effectiveness is frequently restricted by its low solubility, stability, and bioavailability. This paper offers a thorough synopsis of the developing field of phytomedicine drug delivery based on CND. It explores CND synthesis processes, surface functionalization strategies, and structural and optical characteristics. Additionally, the advantages and difficulties of phytomedicine are examined, with a focus on the contribution of drug delivery methods to the increased effectiveness of phytomedicine. The applications of CNDs in drug delivery are also included in the review, along with the mechanisms that underlie their improved drug delivery capabilities. Additionally, it looks at controlled release methods, stability augmentation, and phytomedicine loading tactics onto CNDs. The potential of polymeric carbon nanodots in drug delivery is also covered, along with difficulties and prospective directions going forward, such as resolving toxicity and biocompatibility issues. In summary, the present review highlights the encouraging contribution of CNDs to the field of drug delivery, specifically in enhancing the potential of phytomedicine for therapeutic purposes.

In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for the efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1 and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7, with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10−5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via sequestration of bio-relevant metal ions (i.e. Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared to that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.

Diabetes is one of the metabolic syndromes that demands the great concern affecting millions of people all over the world. Viral infections were also considered as responsible for diabetes. Though, variety of medications for prevention and treatment of diabetes are available, numerous limitations are also prevailing that cannot be neglected. Precise drug-targetability, controlled drug-release, oral bioavailability, minimizing side effects are a few to consider. To address most of these shortcomings of traditional drug-delivery models, nanoformulation has been employed therein a wide range of nanoformulation models are developed. The pharmacology of a drug can be greatly enhanced through nanoformulation models in diabetes treatment in terms of enhanced bioavailability, prolonged and sustained drug-lease, maintain maximum drug concentration in serum, higher intestinal absorption, and protection from enzymatic degradation. In this review work, recently designed nanoformulation models for efficient insulin delivery and the other properties concerning diabetes such as reducing blood glucose level, total cholesterol, triglycerides, lipid profile, wound healing, elevating antioxidant enzymes etc. are discussed. Classification of the nanoformulation models is done based on the nature of the fabricating material employed in nanoformulation. This review may be helpful in designing a more efficient nanoformulation model for diabetes treatment.

Mississippi youth are demographically unique compared to that of the nation. The purpose of this study was to determine the trend of drug use among adolescents of the United States and Mississippi, and to estimate the differences of drug use prevalence as a whole, and by gender and by race. National and Mississippi YRBSS data from 2001 to 2021 were obtained for analysis. Summary statistics, prevalence ratio, and survey Chi-squared tests of independence statistics were generated for the comparison for all students, and by gender and race separately. Trend analysis was conducted using logistic regression combined with joinpoint regression. Six survey questions being studied were: have you ever used marijuana, inhalant, heroin, methamphetamines, injected drugs, and were you offered, sold, or given an illegal drug on school property during the last 12 months. Survey packages in R were used to account for the complex sampling design of YRBSS data. On the national level, all six drug related risk behaviors being studied showed significant decrease from 2001 to 2021. In Mississippi however, only “ever used marijuana” showed a trend of decrease, while three remain unchanged, and two increased. 2021 YRBSS data shows that Mississippi adolescents exhibited significantly higher prevalence of drug use, and are more likely to be offered, sold or given an illegal drug on school property. Our study suggests an urgent need for drug use intervention among Mississippi adolescents. More concerted actions at the community, school and government level are needed for reducing youth drug use and controlling the drug traffic on school property.

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinical data demonstrate that only 5% of Long COVID anosmia patients have fully recovered during the past 2 years and 10.4% of COVID patients are still symptomatic 18 months post infection. Our group demonstrated that ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound in nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to resto-ration of neurologic functions. The objective of the current study is to evaluate the mucociliary safety of the EC16m nasal nanoformulations and the efficacy against human coronavirus. Meth-ods: nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using MucilAir Human Nasal Epi-thelium Model; contact antiviral activity and post-infection inhibition against OC43 viral strain were assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: the saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference in comparison to saline (0.9% NaCl) on tissue integrity, cytotoxicity, and cilia beat fre-quency. A 5-minute contact inactivated 99.9% of the β-coronavirus OC43. OC43 viral replication was inhibited by >99% after infected MAR-5 cells were treated with one of the formulations. Con-clusion: the saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety measurements comparable to saline, a solution widely used for nasal applications.

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

Hiccups can significantly reduce the quality of life of patients and can occur as a drug side effect. Previous report using the Drug Adverse Event Database revealed sex-specific differences in the incidence of drug-induced hiccups. However, the pathogenesis of drug-induced hiccups remains unknown, and there is limited evidence on its treatment or prevention. This study examined molecular initiating events (MIEs), which are the starting point of adverse events, to investigate the drug-induced pathways of hiccups. We extracted drugs suspected to cause hiccups using FDA Adverse Event Reporting System, a large database on adverse drug reactions. Information on drugs suspected to be associated with hiccups were extracted from the overall population and sex-specific subgroups divided. In each data table, the predicted activity values of nuclear receptors (NRs) and stress response pathways (SPs) for each drug were calculated using the toxicity predictor, a machine-learning model. Univariate analysis extracted NRs and SPs associated with hiccups, and a multivariate analysis was performed to evaluate independent factors. Transforming growth factor-beta and antioxidant response element were considered an independent factor for hiccups in the male and female subgroups, respectively. This report first examined one of the mechanisms of drug-induced hiccups and identified MIEs associated with drug-induced hiccups.

The active form of fingolimod (FTY720; FT) is a sphingosine-1-phosphate receptor agonist with potential ocular applications. The goal of the present study was to develop an FT-loaded nanoemulsion (NE; FT-NE) formulation for the efficient and prolonged delivery of FT to the posterior segment of the eye through the topical route. FT-NE formulations were prepared with homogenization followed by probe sonication method. The lead FT-NE formulation (0.15% and 0.3% w/v loading), comprising soybean oil as lipid and Tween® 80 and Poloxamer 188 as surfactants, was further evaluated for in vitro release, surface morphology, filtration sterilization, and stability at refrigerated temperature. The formulation, at both dose levels, showed desirable physicochemical characteristics, a nearly spherical shape with homogenous nanometric size distribution, and was stable for 180 days (last time point checked) at refrigerated temperature post-filtration through polyethersulfone (0.22 µm) membrane. In vitro release studies showed prolonged release, compared with the control FT solution (FT-S), over 24 h. The results from these studies demonstrate that the FT-NE formulation can serve as a viable platform for the ocular delivery of FT through the topical route.

Persons who inject drugs (PWIDs) represent an important reservoir of hepatitis C virus (HCV) infection, hence therapeutic communities (TCs) are promising points of care for the identification and treatment of HCV-infected PWIDs. We evaluated the effectiveness and efficacy of an HCV micro-elimination program targeting PWIDs in the context of a drug-free TC applying Cascade of Care (CoC) evaluation by calculating frequencies of infection diagnosis, confirmation, treatment and achievement of a sustained virological response (SVR). We also evaluated the risk of reinfection of PWIDs achieving HCV eradication, by collecting follow-up virologic information of previously recovered individuals and eventual relapse in drug use, assuming the latter as a potential source of reinfection. We considered all PWIDs (aged 18+ years) residing in the San Patrignano TC at the beginning of the observation period (Jan/2018–Mar/2022) or admitted thereafter, assessing for HCV and HIV serology and viral load by standard laboratory procedures. Ongoing infections were treated with direct acting antivirals (DAA), according to the current national guidelines. Out of the 792 individuals tested on admission, 503 (63.5%) were found to be seropositive for antibodies against HCV. 481 of these 503 individuals (95.6%) underwent HCV-RNA testing. Out of the 331 participants positive for HCV-RNA, 225 were ultimately prescribed a DAA treatment with a Sustained Viral Response (SVR), which was achieved by 222 PWIDs (98.7%). 186 of 222 PWIDs (83.8%) with SVR remained HCV-free on follow-up (with a median follow-up of 2.73 years after SVR ascertainment). The CoC model in our TC proved efficient in implementing HCV micro-elimination, as well as in preventing reinfection and promoting retention in care of individuals, which aligns with the therapeutic goals of addiction treatment.

The reproductive health of women is governed by an optimal balance between the host-microbiota interaction. Depletion in the beneficial vaginal microflora caused by depletion of Lactobacillus species and increased proliferation of pathogens results in gynecological infections. Among women of reproductive age, vaginal infections are increasingly prevalent. Attaining therapeutic efficacy using conventional formulations remains a challenge as vaginal fluids quickly remove or dilute the therapeutic formulations. Hydrogels have been widely exploited for targeted delivery of therapeutics directly into the vaginal mucus. With careful choice of polymers (natural, synthetic or semi-synthetic) hydrogels with specific properties such as stimuli-responsiveness, antimicrobial, and muco-adhesiveness can be tailored for higher therapeutic efficacy. In this review, the advnances in hydrogel strategies for the treatment of vaginal infections is presented with emphasis on the types and properties that play a significant role in vaginal drug delivery systems.

Progress in understanding the pathogenesis and treatment of Alzheimer's disease (AD) is based on the recognition of the primary causes of the disease, which can be deduced from the knowledge of risk factors and biomarkers measurable in the early stages of the disease. Insights into risk factors and the time course of biomarker abnormalities point to a role for mitochondrial dysfunction and oxidative stress in the onset and development of AD. Coenzyme Q10 (CoQ10) is a lipid antioxidant and electron transporter in the mitochondrial electron transport system. The availability and activity of CoQ10 is crucial for proper mitochondrial function and cellular bioenergetics. Based on the mitochondrial hypothesis of AD and the hypothesis of oxidative stress, the regulation of the efficiency of the oxidative phosphorylation system by means of CoQ10 can be considered promising in restoring the mitochondrial function impaired in AD, or in preventing the onset of mitochondrial dysfunction and the development of amyloid and tau pathology in AD.

Polyelectrolyte multilayers (PEMs) deposited on porous composite polylactic acid/poly(ε-caprolactone) substrates were studied. The substrates were previously charged in a corona discharge. Time dependences of the normalized surface potential for positively and negatively charged electrets were investigated. The morphology of the obtained porous substrates was examined by means of scanning electron microscopy (SEM). The chitosan and the casein polyelectrolytes were deposited on the substrates using the layer-by-layer (LbL) technique. A drug loading efficiency and the release kinetics were determined spectrophotometrically.

Over the few decades, cancer-associated mortalities and morbidities were continuously increased worldwide despite sophisticated technological advancements. Pharmaceutical interventions associated with drugs exhibit a high degree of side effects and toxicities in addition to very high costs. Subsequently, to reduce or to vanish the side effects and high costs, researchers are now exploring natural bioactive compounds such as quercetin in its nanoformulations along with biologics as cargo delivery vehicles. Quercetin along with mesenchymal stromal lineage-derived extracellular vesicles (EVs) possesses an anti-cancer potential that can be explored to treat hepatocellular carcinoma (HCC). Exerting enhanced effect, nano quercetin synergistically with EVs triggers the anti-cancer mechanisms by regulating and dysregulating several signalling mechanisms including NF-κB, p53, JAK/STAT, MAPK, Wnt/β-catenin and PI3K/AKT, in addition to PBX3/ERK1/2/CDK2, and miRNAs modulation. In addition, findings regarding the potential checkpoints of anti-cancer signalling pathways were investigated that offer opportunities to develop engineered EVs incorporated with nano quercetin for the development of novel therapeutics to treat HCC in future. In this present mechanistic review, we abridged the regulation of such signalling mechanisms synergetic approach of nano quercetin and EVs. The regulatory role of EVs in the manifestation of innumerable miRNAs has also been tailed with special context to HCC.

Zika Virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique charac-teristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the ab-sence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce in vitro infection of A549 epithelial cells, a well-known cell model for flaviviruses infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to down-regulate adiponectin receptor expression and thereby limit adi-ponectin signaling.

The integration of bioinformatics in drug discovery has revolutionized the field of pharmaceutical research. The use of computational tools and techniques has enabled researchers to analyze vast amounts of data, identify potential drug targets, and design new drugs with greater precision and efficiency. The integration of bioinformatics has also facilitated the development of personalized medicine, where drugs can be tailored to individual patients based on their genetic makeup. However, there are still challenges that need to be addressed, such as the need for more accurate predictive models and the ethical considerations surrounding the use of patient data. Overall, the integration of bioinformatics in drug discovery holds great promise for improving human health and advancing our understanding of disease mechanisms. In this mini-review, we discuss how Bioinformatics plays a crucial role in each step of drug discovery by providing tools and techniques to analyze large amounts of data generated from various sources, as well as the challenges and the opportunities offered by bioinformatics.

(1) Background: The incidence of vancomycin-induced neutropenia in hospitalized patients is estimated to be around 2 to 8 percent [1,2]. Data surrounding vancomycin-induced neutropenia is limited as it is based on a small number of observational case reports. Additionally, it is difficult to provide generalized conclusions since patient characteristics and indications for treatment vary between reports. (2) Case Reports: We present two cases of vancomycin-induced neutropenia that occurred at our facility; a 50-year-old male who developed neutropenia after treatment with vancomycin for a gluteal abscess and a 51-year-old female who developed neutropenia after treatment with vancomycin for lumbar osteomyelitis. In both cases, neutropenia resolved within 2 days of discontinuation of vancomycin. (3) Conclusion: The risk of developing neutropenia increases with age, prolonged drug exposure, decreased renal clearance, and in those of female sex. Treatment involves discontinuation of vancomycin with or without administration of granulocyte colony-stimulating factor (G-CSF). Additional studies are needed to better understand the true incidence of this adverse drug reaction and to identify risk factors that may predispose patients to vancomycin-induced neutropenia.