Although Cucurbita pepo is one of the most variable species of the plant kingdom, Zucchini morphotype has undergone intensive breeding that has led to a narrow genetic base making the crop vulnerable to pest and diseases. This vulnerability makes the knowledge of resistance genes of utmost importance. In this study, a data mining search of Zucchini summer squash genome database was conducted to identify and annotate members of the NBS-encoding gene family. In order to characterize the retrieved genes in detail, they have been studied in the bases of phylogenetic relationships, structural diversity, conserved protein motifs, gene duplications and promoter region analysis. Our study shows that the NBS-encoding gene family is relatively small in Zucchini (34 members, which are separated into non-TIR- and TIR-NBS-LRR subfamilies) with a significantly lower number of R-genes than in other species. Duplications have not played a major role in the expansion of this type of genes in C. pepo. Among the cis-regulatory elements presented in these sequences, six motifs are over-represented. These elements were reported to be involved in pathogens or plant stress induced responses. These results will contribute to the identification, isolation and characterization of candidate R-genes, thereby providing insight into NBS gene family evolution in the species.

Impact in the form of innovation and commercialisation is an essential component of publicly funded research projects. PHUSICOS, an H2020 Innovation Action project, aims at demonstrating the use of nature-based solutions for mitigating hydrometeorological hazards in rural and mountainous areas. The work program is built around key innovation actions, and each WP leader specifically responsible for nurturing innovation processes, maintaining market focus and ensuring relevance for the intended recipients of the project results. Key success criteria for PHUSICOS include up-scaling and mainstreaming of NBS to reach broader market access. An innovation strategy and supporting tools for implementing this within PHUSICS has been developed and key concepts forming the basis for this strategy are presented in this research note.

Rice blast is the most harmful disease caused by Magnaporthe oryzae, leading to yield loss. The aim of the work is to improve resistance of rice to blast by introducing and pyramiding genes using conventional breeding technique and modern MAS analysis. Pyramiding is the combination of several resistance genes in one genotype, in this case it improves the resistance of rice to pathogens. MAS analysis revealed that 3 out of 4 studied domestic high-yielding rice cultivars (Bakanasski, Aisaule and Aru) contain 1 blast resistance gene (Pi-2). It was discovered 7 pyramidal lines with the introduction of a combination of 2 blast resistance genes (Pi-1 and Pi-ta) into 6 hybrids and 3 genes (Pi-1, Pi-33 and Pi-ta) into 1 line. Phytopathological test of local cultivars and pyramidal lines of rice showed that 3 out of 7 pyramidal lines have moderate resistance: 2 lines (F2 Bakanasski/7667 (var. vulgaris Koern.) and F2 Aisaule/7664 (var. italica Alef.)), containing 2 resistance genes (Pi-1 and Pi-ta) and 1 line – F2 Aisaule/7689 (var. zeravschanica Brsch.), carrying 3 genes (Pi-1, Pi-33 and Pi-ta), while the local cultivars Bakanasski, Aisaule and Aru are susceptible. As a result, the blast resistance of rice was improved by creating pyramidal lines. Pyramided lines can be used for germplasm exchange and in rice breeding programs to improve blast resistance in rice.

Carbapenem antibiotics are the drug of choice for treating multidrug-resistant bacterial infections. Metallo-beta-lactamases (MBLs) are carbapenemase capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, a need to assess the frequency and phenotypic resistance phenomena of two MBL genes in diarrheal and urinary tract infections (UTIs). Samples were collected through a cross-sectional study, with MBLs genes detected via PCR. Two hundred twenty eight diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively.  Total 142 UTI pathogens were obtained from 150 urine samples, with Klebsiella spp. (39%) and Escherichia coli (24%) are the major pathogens. Phenotypic resistance to amoxycillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively.  Twenty four diarrheal isolates carried either blaNDM-1 or blaVIM genes; the overall MBL gene prevalence was 10.5%. Thirty six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes.  MBL genes exhibited a strong association with phenotypic carbapenem and other beta-lactam antibiotic resistance. Resistance to carbapenems requires active surveillance and stewardship.

Rising antimicrobial resistance (AMR) in Salmonella serotypes host-adapted to cattle is of increasing concern to the beef and dairy industry. The bulk of the existing literature focuses on AMR post-slaughter. In comparison, the understanding of AMR in Salmonella among pre-harvest cattle is still limited, particularly in Texas, which ranks top five in beef and dairy exports in the United States; inherently, the health of Texas cattle has nationwide implications for the health of the United States beef and dairy industry. In this study, long-read whole genome sequencing and bioinformatic methods were utilized to analyze antimicrobial resistance genes (ARGs) in 98 isolates from beef and dairy cattle in the Texas Panhandle. Fisher exact tests and elastic net models accounting for population structure were used to infer associations between ARGs and antimicrobial phenotypic profiles and metadata. Gene mapping was also performed to assess the role of mobile genetic elements in harboring ARGs. ARG were found to be statistically different between the type of cattle operation and Salmonella serotypes. Beef operations were statistically significantly associated with more resistance genes compared to dairy operations. Salmonella Heidelberg, followed by Salmonella Dublin isolates, were associated with the most ARGs. Additionally, specific classes of ARGs were only present within mobile genetic elements.

Water samples for bacterial microbiome studies undergo a biomass concentration, DNA extraction and taxonomic identification steps. Through benchmarking, we studied the applicability of Skimmed milk flocculation (SMF) for bacterial enrichment, an adapted in-house DNA extraction protocol, and six 16S rRNA databases (16S-DBs). Surface water samples from two rivers were treated with SMF and Vacuum filtration (VF) and subjected to amplicon or shotgun metagenomics. A mock community standard underwent five DNA extraction protocols, taxonomical identification with six different 16S-DBs and evaluated by the Measurement Integrity Quotient (MIQ) score. In SMF samples, the skimmed milk was metabolized by members of lactic acid bacteria or genera such as Polaromonas, Macrococcus, and Agitococcus, resulting in increased relative abundance (p < 0.5) up to 5.0 log fold change compared to VF, rendering SMF inapplicable for bacterial microbiome studies. The best performing DNA extraction protocols were FastSpin Soil, the in-house method and EurX. All 16S-DBs yielded comparable MIQ scores within each DNA extraction kit, ranging from 61-66 (ZymoBIOMICs) up to 80-82 (FastSpin). DNA extraction kits exert more bias to the composition than the 16S-DBs. This benchmarking study presented valuable insights to inform future water metagenomic study designs.

The emergence of antimicrobial resistance (AMR) in pathogens transmitted through food poses a significant threat to global public health, complicating infection treatment and increasing mortality rates. This review explores the role of resistome mapping as a crucial tool for understanding the transmission dynamics of antimicrobial resistance genes (ARGs) in foodborne pathogens, such as Salmonella, Escherichia coli, Listeria monocytogenes, and Campylobacter spp., as well as various techniques for resistome mapping, such as metagenomic sequencing, PCR-based methods, and whole-genome sequencing (WGS), highlighting the significance of horizontal gene transfer (HGT) as a key mechanism for ARG dissemination in foodborne pathogens. Additionally, we investigated the influence of agricultural practices and environmental factors on AMR development, highlighting the critical need for improved surveillance, antibiotic stewardship, and global collaboration to mitigate the spread of resistant ARGs through the food chain. The perceptions gained from resistome mapping play an essential role in developing effective approaches to address AMR and to ensure food safety.

Background: The resurgence of syphilis, primarily in MSM populations, has necessitated novel prophylactic strategies, such as the use of doxycycline post-exposure prophylaxis (doxy-PEP). However, the potential for increased doxycycline use to select for tetracycline resistance represents significant challenges in managing this sexually transmitted infection. This study aims to identify chromosomal mutations associated with tetracycline resistance in Spirochaetales to inform treatment strategies and surveillance measures.Methods: Whole genome sequences (WGS) from the Spirochaetales order, including 4,355 genomes, were analyzed for the presence of mutations in 16S rRNA and non-synonymous mutations in the rpsC and rpsJ genes. The study utilized WGS from GenBank® and sequence data from the PubMLST Treponema pallidum isolate collection. Genetic resistance to tetracycline was detected using a combination of BLASTN searches and gene-gene analysis. Results: A transition mutation TGA to TGG at positions 965-967 in the 16S rRNA gene was detected in 5.6% of Treponema spp. and 3.97% of Spirochaeta spp. genomes. The rpsJ gene exhibited a V57G amino acid substitution across a significant subset of Treponema spp. Notably, the V57K mutation was common in Spirochaeta spp. The rpsC gene had the H178Q mutation and was found to be present in the Spirochaetales bacterium.Conclusion: The identification of mutations associated with tetracycline resistance in Spirochaetales provides a foundation for the development of rapid molecular diagnostics and guides the clinical selection of antibiotics for syphilis treatment. This study underscores the complexity of antibiotic resistance mechanisms and the critical importance of surveillance in the era of antibiotic prophylaxis for STI management.

Antibiotic resistance is a global health problem. The human gut microbiome is implicated in the dynamics of antibiotic resistance acquisition and transmission, with the gut microbiota thought to play a crucial role. This study aimed to determine the potential influence of human gut bacteria microbiota on the gut resistome and the relationship between gut background microbiota and Escherichia coli resistome. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines was used to systematically review studies that characterised gut microbiota and resistome using metagenomic analysis and/or those that reported gut E. coli resistome in healthy individuals. Changes in the diversity and abundance of bacterial gut microbiota and the resistome across different groups and the microbiota composition of the gut harbouring antibiotic-resistant E. coli were summarised. Findings suggest that lower bacterial microbiota diversity is likely associated with an increased abundance of the overall gut resistome. Age-related differences were observed, with younger infants exhibiting lower microbiota diversity and higher ARG abundance compared to older infants and adults. Studies that reported correlation revealed positive correlations between the compositional relative abundance of Proteobacteria and ARGs abundance, mainly driven by members within the Enterobacteriaceae family, particularly E. coli. This study also revealed that human gut microbiome studies that investigate gut resistome using metagenomic sequencing approaches in apparently healthy individuals are at least uncommon.

The global antibiotic resistance crisis, driven by antibiotic overuse and misuse, is multifaceted. This study aimed to assess the microbiological and genetic characteristics of raw retail pork meat, including the isolation, antibiotic susceptibility testing (AST), whole genome sequencing (WGS) of selected indicator bacteria, antibiotic residue testing, and metagenomic sequencing. Samples were purchased from 10 randomly selected retail stores in Gauteng, South Africa. Samples were aseptically separated, with a portion sent to an external laboratory for isolating indicator bacteria and antibiotic residue testing. Identification of the isolated bacteria was reconfirmed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). AST was performed using the Microscan Walkaway system. WGS and metagenomic sequencing were performed using the Illumina NextSeq 550 instrument. The isolated E. coli and enterococci exhibited little phenotypic resistance, with WGS revealing tetracycline resistance genes. Isolated bacteria and meat samples all harboured tetracycline resistance genes, and the antibiotic residue concentrations were within acceptable limits for human consumption. In the metagenomic context, most identified bacteria were of food/meat spoilage and environmental origin, with the resistome analysis primarily indicating beta-lactam, tetracycline and multidrug resistance genes. Further research is needed to understand the broader implications of these findings on environmental health and antibiotic resistance.

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.

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.

Coronavirus disease-19 (COVID-19) has disproportionately affected certain demographics in England, exacerbating existing health disparities. Effective therapeutics are a critical line of defence against COVID-19, particularly for patients at elevated risk for severe disease. Surveillance systems were established to monitor usage of COVID-19 therapeutics in hospital and community settings and inform stewardship. Three antiviral therapies: nirmatrelvir plus ritonavir (Paxlovid®), remdesivir (Veklury®), and molnupiravir (Lagevrio®); and two neutralising monoclonal antibody therapies (nMAbs): sotrovimab (Xevudy®) and casirivimab with imdevimab (Ronapreve®); were in use in England between July 2020 to April 2023. This paper aims to illuminate trends in the utilisation of COVID-19 therapeutics treatment in both hospital and community settings, stratified by the Index of Multiple Deprivation (IMD) in England. Chapter 3 of the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) report 2022 to 2023 also discusses the epidemiological surveillance of these five directly-acting antiviral COVID-19 therapeutics use in England between 2022 to 2023.

Porcine parvovirus 8 (PPV8), a novel virus in the Parvoviridae family, was first identified in 2022 in lung samples of domestic pigs from China. Retrospective analyses showed that it had been circulating in China since 1998, but no other countries had reported its presence so far. A recent study conducted in South America did not detect any PPV8-positive samples in that region. Here we report the detection of PPV8 in Hungarian and Slovakian pig farms and the estimated prevalence of the virus in Hungary. Altogether 2230 serum, 233 oral fluid, and 115 processing fluid samples were systematically collected from 23 Hungarian and 2 Slovakian pig farms between 2020 and 2023. A real-time quantitative PCR method was developed to detect the viral genome. Our results revealed the presence of PPV8 on 65% of the Hungarian farms and on both Slovakian farms included in our study, marking its first detection in Europe. Oral fluid samples showed the highest positivity rates, reaching up to 100% in some herds. The viral genome was successfully detected in serum and processing fluid samples too, but with significantly lower prevalence rates of 4% and 5%, respectively. Genetic analysis of 11 partial VP2 sequences demonstrated high similarity to the original Chinese strain but with unique amino acid mutations, suggesting possible local evolution of the virus. Our study presents the first scientific evidence of PPV8 infection outside of China and offers a comprehensive assessment of its prevalence in the Hungarian pig population. Further research is required to understand its potential impact on swine health.

Powdery mildew is a severe disease causing substantial yield losses in wheat production worldwide. The Chinese wheat landrace Changanhongmai (CAHM) exhibits high resistance to the physiological race E09 of powdery mildew. This study aims to characterize the powdery mildew resistance gene in CAHM, and develop molecular markers for marker-assisted selection of wheat. To investigate the genetic characteristics of this resistant gene, we developed F1 plants, F2 generation population, and F2:3 families from a cross between CAHM and SY225. Genetic analysis demonstrated that all F1 plants were resistant to the disease, while the ratio of resistant to susceptible plants was 3: 1 in both the F2 population and F2:3 families, indicating that CAHM is inherited in a manner of single dominant powdery mildew resistance gene, which was tentatively designated as PmCAHM. By using bulk segregation analysis, we constructed a genetic map encompassing Xgwm273, Xwmc626, Xgwm11, Xgwm18, Xgdm28, Xgpw7812, Xgpw5195, Xwmc694 and PmCAHM. Among these markers, Xgpw7812 and Xgpw5195 were flanking markers tightly linked to PmCAHM at a genetic distance of 2.5 cM and 8.4 cM, respectively. Furthermore, nullisomic-tetrasomic analysis revealed that PmCAHM is located on chromosome 1B. These results indicate that PmCAHM differs from the internationally recognized powdery mildew resistance genes in both location and source. In addition, a new germplasm/line NW1748 with large seeds and powdery mildew resistance was developed from the cross and back cross populations of Fengyou 1718 (FY1718)/CAHM//FY 1718. Therefore, PmCAHM can serve as a novel powdery mildew resistance source for breeding of wheat by using NW1748 as the donor in the future.

Antibiotic resistance of cyanobacteria has been a global threat to public health. The widespread presence of cyanobacteria in aquatic environments exposes them to antibiotic contamination. The cyanobacteria are also in direct contact with pathogenic bacteria containing Antibiotic-Resistance Genes (ARGs) that gives them these characteristics. The study aims to the presence of some ARGs in locally isolated cyanobacteria species, Spirulina laxa, Chroococcus minutes, Oscillatoria princeps, Oscillatoria proteus, Oscillatoria terebriformis, Lyngbya epiphytica, and to compare the presence of these genes in two pathogenic bacteria, Escherichia coli and Klebsiella pneumoniae. The results revealed the presence of The ampicillin (Ap) and erythromycin (Em) resistance genes were detected in five algal samples. Meanwhile, the chloramphenicol (Cm) and gentamicin (Gm) resistance genes were apparent in only two species. Genes encoding resistance towards kanamycin (Km) and spectinomycin (Sp) were recorded in three specimens. The results also documented that E. coli possessed the resistance genes for four antibiotics: Ampicillin (Ap), Erythromycin (Em), Gentamicin (Gm), and Kanamycin (Km), whereas K. pneumoniae was resistant towards three anti-biotics: Ampicillin (Ap), Gentamicin (Gm), and Kanamycin (Km). The results show that there are a match in antibiotic resistance genes in both cyanobacteria and pathogenic bacteria. suggesting the possibility that cyanobacteria could acquire ARGs from the environment through horizontal gene transfer. Thus, freshwater cyanobacteria may play an important role in the prevalence of ARGs in their environment.

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

Sodium hypochlorite (NaOCl) is widely used in public healthcare facilities; this exposure can result in the development of bacterial tolerance to disinfectant, which has known links to antibiotic cross-resistance. However, the mechanism through which cross-resistance to antibiotics and disinfectants develops remains ambiguous. Therefore, this study aimed to examine the phenotypic, and transcriptomic changes caused by disinfectant exposure in gram-negative bacteria and determine the cause of cross-resistance to antibiotics. The results demonstrated that the misuse of disinfectants plays an important role in the emergence of disinfectant resistance and in the increase in antibiotic resistance. Antibiotic resistance may occur from exposure of gram-negative bacteria to subminimal inhibitory concentrations (MICs) of NaOCl. Ten passages of gram-negative bacteria in increasingly higher subMICs of NaOCl disinfectant was sufficient to increase the MIC to &gt;2,500 µg/ml NaOCl, particularly in K. pneumoniae and P. aeruginosa. To determine the development of cross-resistance to antibiotics due to NaOCl exposure, the MICs for each antibiotic before and after exposure of each strain to sublethal concentrations of NaOCl were compared. After overnight incubation with a sublethal concentration of NaOCl, a statistically significant increase in MIC was only observed for imipenem (P&lt;0.01). Investigation of the mechanism of cross-resistance by means of transcriptome analysis revealed that 1,250 µg/ml NaOCl-adapted K. pneumoniae and P. aeruginosa strains increased resistance to imipenem due to increased expression of the resistance-nodulation-cell division (RND) efflux pumps, such as AcrAB-TolC and MexAB/XY-OprM. Therefore, we suggest that exposure to NaOCl can influence the expression of RND efflux pump genes, contributing to imipenem cross-resistance.

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.

Background Polycystic ovary syndrome (PCOS) is a common hormonal disorder worldwide among women of reproductive age. It is characterized by endocrine, reproductive, and metabolic abnormalities. Insulin resistance (IR) is one of its most important clinical features, associated with metabolic disorders and increased risk of type 2 diabetes (T2D). This study aimed to explore the whole blood gene expression profiling related to IR in PCOS patients compared to controls. Methods Blood RNA was extracted from 5 PCOS and 5 non-PCOS women with matched age and BMI. Homeostasis model assessment (HOMA-IR) was used to estimate the IR. The expression of IR genes was analyzed by Profiler PCR array. Results Both groups have similar levels of HOMA-IR (p>0.05). However, differential expression levels were observed between them. Fourteen genes were upregulated and 26 genes were downregulated in PCOS samples. Among the upregulated genes (>2 fold-change, p-value<0.05) are ADIPOQ, ADIPOR1, OLR, IGF-1, and APOE. Downregulated genes (>-2 fold-change, p-value<0.05) include HK-2, IRS1, and SERPINE1. These genes are involved in insulin and adipokines signaling, commonly dysregulated in T2D. They are also involved in innate immunity and inflammatory processes and are essential for lipid and carbohydrate metabolism. Conclusion Our finding suggests that despite both groups having no difference in IR level, there are differentially expressed genes involved in the IR pathway.

Drought and arsenic contamination pose a serious threat to global rice crop yield. Existing solutions focus on either heavy metal or drought remediation, but not both. Examination of the Oryza sativa metagenome via the National Center for Biotechnology Information (NCBI) database revealed promising candidates within the aquaporin gene family capable of efficiently mitigating both arsenic toxicity and drought stress. Rice cotyledons were genetically augmented with arsenic-resistant OsNIP2;1 and OsNIP3;2 genes, and drought-resistant OsPIP2;2 genes. In moderate drought conditions and 25 ppm arsenic-contaminated soil, transgenic plants showed drought tolerance and reduced translocation of arsenic from root to shoot. Soil arsenic levels plummeted from 25 ppm to 5 ppm, demonstrating the strategy's efficacy. Statistical significance was confirmed using T tests. Thus, aquaporin-augmented Oryza sativa offers a promising solution to mitigate both arsenic and drought stress in rice plants improving crop yield and facilitating soil decontamination.

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

Clopidogrel is one of the thienopyridine antiplatelet drugs commonly used as a prophylactic medication to prevent coagulation in vessels and cardiovascular events. The molecule of clopidogrel is metabolized in the liver via phase-I and phase-II metabolism pathways. The sulfenic acid clopidogrel metabolite undergoes phase-II metabolism through conjugation with glutathione by the glutathione-s-transferase (GST) to form a glutathione conjugate of clopidogrel (inactive metabolite). A glutaredoxin enzyme removes the glutathione conjugated with clopidogrel to form cis-thiol-clopidogrel. This review focused on the polymorphisms of genes related to phase-II metabolism during the clopidogrel bioactivation process. Overall, no well-controlled studies were done about the relationship between the clopidogrel bioactivation process and genes related to phase-II metabolism’s enzymes. Nevertheless, some polymorphisms of G6PD, GCLC, GCLM, GSS, GST, GSR, HK, and GLRX genes could be responsible for clopidogrel resistance due to low glutathione conjugate or glutaredoxin plasma levels. Studies needed to be concerned with the relationship between clopidogrel resistance and phase-II metabolism issues in the near future.

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

Globally, rice is utilized as staple food, belongs to the family Poaceae. From the past few decades under variable climate conditions, it greatly affected by the bacterial leaf blight (BLB) disease caused by a bacterium Xanthomonas oryzae pv. oryzae (Xoo). Scientists studied causes of the disease and found more than 61 isolates of Xoo. About 39 Xa genes were noted that cause race specifically resistance either individually or in pairs against Xoo. The canvas on the characterization of these genes is still unrevealed. In this study, amino acid sequences of Xa15, Xa19, Xa20 and Xa21 were mined and used for motif-domain identification, characterization, and comparative analysis. It includes screening of physical and chemical characteristics, sequence comparison to find sequence similarity between them and their phylogenetic comparison with other Xa genes and other species based upon LRR and S_TKc domains to find evolutionary relationship among them. The comparison-based modeling was performed and assessed by different tools to gain better understanding and structural evaluation. The results showed identified domains are specific in function, each domain involved in resistance against biotic and abiotic stresses through regulating different cellular processes. This study also revealed high similarity (>98% sequence identity) between these genes and encode a similar leucine-rich repeat receptor kinase like protein. It will optimize the breeding programs as it will be useful for the selection of effective genes to produce resistance in rice varieties against the specific strains of Xoo that will be more effective against BLB than the other Xa genes.

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.

Stalk rot caused by Fusarium fungi is one of the most widespread and devastating diseases of maize, and the introduction of resistant genotypes is one of the most effective strategies for controlling the disease. Breeding genotypes with genetically determined resistance will also allow less use of crop protection products. The aim of the research was to identify molecular markers and associated candidate genes determining maize plant resistance to Fusarium stalk rot. The plant material for the study consisted of 122 maize hybrids, which were sown in plots of 10 m2, in a complete randomized block design, in three repetitions, at two locations (Smolice: 51 42’ 58.904’’ N, 17 13’ 29.13’’ E and Kobierzyce: 50 58’ 19.411’’ N, 16 55’ 47.323’’ E). The analyzed genotypes were simultaneously subjected to next-generation sequencing using the Illumina platform. The results of the observation of the degree of infection and sequencing were used for association mapping, which ultimately resulted in the selection of 10 molecular markers important at both places. Among the identified markers, two SNP markers that are located inside candidate genes play an important role. Marker 4772836 is located inside the serine/threonine-protein kinase bsk3 gene, while marker 4765764 is located inside the histidine kinase 1 gene. Both genes can be associated with plant resistance to Fusarium stalk rot, and these genes can also be used in breeding programs to select resistant varieties.

Background: In France, no previous studies had addressed the acquisition of multidrug resistant (MDR) bacteria and colistin resistance genes by medical students when undertaking internships abroad. Methods: Nasopharyngeal, rectal, and vaginal swabs samples were collected from 382 French medical students before and after travel to investigate the acquisition of MDR bacteria. The bacterial diversity in the samples was assessed by culture on selective media. We also genetically characterised the isolates of MDR bacteria including Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E), methicillin-resistant Staphylococcus aureus (MRSA), and Carbapenemase-producing Enterobacteriacae (CPE) using the real-time polymerase chain reaction method. The samples were collected from 293 students and were investigated for mcr colistin-resistance genes using RT-PCR directly on the samples, followed by conventional PCR and sequencing. Results: A proportion of 29.3% of the participants had acquired ESBL-E and 2.6% had acquired CPE. The most common species and ESBL-E encoding gene were Escherichia coli (98.4%) and bla_CTX-M-A (95.3%), respectively. A proportion of 6.8% of the participants had acquired mcr-1 genes, followed by mcr-3 (0.3%) and mcr-8 (0.3%). We found that taking part in humanitarian missions to orphanages, being in contact with children during travel, the primary destination of travel being Vietnam and north India, using antibiotics during travel, and studying in 2017 were associated with the acquisition of ESBL-E. When the primary destination of travel was Vietnam and the year of study was 2018, this was associated with acquisition of colistin resistance genes. Conclusion: Medical students are at a potential risk of acquiring ESBL-E, CPE and colistin resistance genes. A number of risk factors have been identified, which may be used to develop targeted preventive measures.

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

Wheat has a large and diverse repertoire of NLRs involved in disease resistance, with over 1,500 NLRs detected in some studies. These NLR genes occur as singletons or clusters containing copies of NLRs from different phylogenetic clades. The number of NLRs and cluster size can differ drastically among ecotypes and cultivars. Primarily, duplication has led to the evolution and diversification of NLR genes. Among the various mechanisms, whole genome duplication (WGD) is the most intense and leading cause, contributing to the complex evolutionary history and abundant gene set of hexaploid wheat. Tandem duplication or recombination is another major mechanism of NLR gene expansion in wheat. The diversity and divergence of duplicate NLR genes are responsible for the broad-spectrum resistance of most plant species with limited R genes. Understanding the mechanisms underlying the rapid evolution and diversification of wheat NLR genes will help improve disease resistance in crops. The present review focuses on the diversity and divergence of duplicate NLR genes and their contribution to wheat disease resistance. Moreover, we provide an overview of disease resistance-associated gene duplication and the underlying strategies in wheat.

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

Rice blast and brown planthopper (BPH) are two of the most destructive diseases and pests in rice (Oryza sativa L.) production in China. The development of multi-resistant varieties is widely recognized as the most efficient and environmentally friendly approach to controlling crop diseases and pests. Functional molecular markers (FMMs) have been developed from functional variants in the genic region associated with trait variation, greatly enhancing the efficiency of identifying and pyramiding valuable genes in crop breeding. In this study, two FMMs and a multiplex PCR amplification system were developed for two major broad-spectrum BPH resistance genes, Bph6 and Bph9. By assistance of FMMs in multi-resistant rice restorer line development pipeline, two lines (Huahui7713 and Huahui3006) with blast and BPH resistance were developed by pyramiding three resistance genes Pigm, Bph6 and Bph9. Huahui7713 and Huahui3006 as male lines, two new hybrid rice varieties (WeiLiangYou7713 and Xuanliangyou3006) were certificated and commercial released in China. WeiLiangYou7713 and Xuanliangyou3006 showed improved blast and BPH resistance, and no penalty on yield and grain-quality. Annual promotion area of WeiLiangYou7713 has exceeded 53.3 thousand hectares, indicating its widespread adoption and success in the market. Huahui7713 and Huahui3006 could have great potential for utilization in blast and BPH resistance rice breeding.

(1) Background: Plasmodium vivax causes the largest malaria burden in Brazil, and chloroquine resistance poses a challenge to eliminating malaria by 2035. Illegal mining in the Roraima Yanomami indigenous territory can lead to the introduction of resistant parasites. This study aimed to investigate mutations in the pvcrt-o and pvmdr-1 genes to determine their potential as predictors of P. vivax chloroquine-resistant phenotypes. (2) Methods: Samples were collected in two health centers of Boa Vista. A questionnaire was completed, and blood was drawn from each patient. Then, DNA extraction, PCR, amplicon purification, and DNA sequencing were performed. After alignment with the Sal-1, the amplified fragment was analyzed. Patients infected with the mutant parasites were queried in the Surveillance Information System. (3) Results: 98% (157/164) of participants were from illegal mining areas. The pvcrt-o was sequenced in 151 samples, and the K10 insertion was identified in 13% of them. The pvmdr1 was sequenced in 80 samples: the MYF haplotype (958M) was detected in 92% of them, the TYF in 8%, while MYL was absent. No cases of recrudescence, hospitalization, or death were found. (4) Conclusions: Mutations in the pvcrt-o and pvmdr-1 genes have no potential to predict chloroquine resistance in P. vivax.

Climate change is impacting the spread/intensity of vector-borne diseases, including malaria, and accelerating evolutionary/adaptive changes in vector species. These changes including chromoso-mal inversions and overexpression and/or changes in allele frequencies of thermotoler-ance-associated genes, may facilitate insecticide resistance through pleiotropy. This study investi-gated the impact of thermotolerance on pyrethroid resistance in four populations of malaria vector An. gambiae, from savanna/sub-Sahel of northern Nigeria. Anopheles coluzzii and An. gambiae were the only malaria vectors found, sympatric in all the sites, with the former species predominant. High thermotolerance was observed, with no mortality at 38°C, and LT50 of ~44°C. Significantly high permethrin resistance was observed (mortality <50%) in heat-hardened (44°C) larvae from two sites, BUK and Pantami, compared with control, and heat-hardened adult females from Auyo (mortality = 3.00%±1.20, χ2 = 5.83, p<0.01) compared with control (12.00%±4.65). The 2La chromosomal inver-sion was detected at ~50% in larvae and 58% in adult females. Significant association was observed (OR = 7.2, p<0.03) between permethrin resistance and 2La/+a rearrangement compared with 2L+a/+a, in BUK larvae. For all sites permethrin resistance correlated with 2La/a homozygosity in adult fe-males [OR = 5.02, p=0.01). qRT-PCR identified 6 genes commonly induced/overexpressed, including heat shock protein 70 (AGAP004581) which was 2468x and 5x overexpressed in heat-hardened and permethrin-resistant females, respectively, trehalose-6-phosphate synthase (AGAP008227), and ionotropic glutamate receptor genes, IR25a (AGAP010272) and IR21a (AGAP008511). This study highlights challenges associated with insecticide-based malaria vector control, and the epidemiological significance of taking climate variables into account for design/choice of control measures.

Background: Multidrug-resistant bacteria present resistance mechanisms against β-lactam antibiotics, such as Extended-Spectrum Beta-lactamases (ESBL) and Metallo-β-lactamases enzymes (MBLs) operon encoded in Gram-negative species. Likewise, Gram-positive bacteria have evolved other mechanisms through mec genes, which encode modified penicillin-binding proteins (PBP2). This study aimed to determine the presence and spread of β-lactam antibiotic resistance genes and the microbiome circulating in Quito’s Public Transport (QTP). Methods: A total of 29 station turnstiles were swabbed to extract the surface environmental DNA. PCRs were performed to detect the presence of 13 antibiotic resistance genes and to identify 16S rDNA barcoding, followed by clone analysis, Sanger sequencing and BLAST search. Results: ESBL genes blaTEM-1 and blaCTX-M-1 and MBL genes blaOXA-181 and mecA were detected along QPT stations. Two subvariants were found for blaTEM-1, blaCTX-M-1, and blaOXA-181. Almost half of the circulating bacteria found at QPT stations were common human microbiota species including those classified by the WHO as pathogens of critical and high-priority surveillance. Conclusions: β-lactam antibiotic resistance genes are widely spread throughout QPT. This is the first report of blaOXA-181 in environmental samples in Ecuador. Moreover, we detected a new putative variant of this gene. Some commensal coagulase-negative bacteria may have a role as mecA resistance reservoirs

Modules composed of a resistance gene flanked by Xer site-specific recombination sites, the vast majority of which were found in Acinetobacter baumannii, are thought to behave as elements that facilitate horizontal dissemination. The A. baumannii xerC and xerD genes were cloned, and the recombinant clones used to complement the cognate Escherichia coli mutants. The complemented strains supported resolution of plasmid dimers, and, as is the case with E. coli and Klebsiella pneumoniae plasmids, the activity was enhanced when cells were growing in low osmolarity growth medium. Binding experiments showed that partially purified A. baumannii XerC and XerD proteins (XerC_Ab and XerD_Ab) bound synthetic Xer site-specific recombination sites, some of them with a nucleotide sequence deduced from existing A. baumannii plasmids. Incubation with suicide substrates resulted in covalent attachment of DNA to a recombinase, probably XerC_Ab, indicating that the first step in the recombination reaction took place. The results described show that XerC_Ab and XerD_Ab are functional proteins and support the hypothesis that they participate in horizontal dissemination of resistant genes among bacteria.

The combination of several therapeutic strategies is often seen as a good way to decrease the resistance rates, since bacteria overcome better single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of Klebsiella pneumoniae persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the K. pneumoniae lytic phage vB_KpnM-VAC13 in vitro and the safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype. At the same time, we verified the absence of toxicity of mitomycin C at the concentration using the human chondrocyte cell line T/C28a2. The viability of these human cells was checked both by cytotoxicity assays and flow cytometry.

Inappropriate antimicrobial treatment can pose a risk for developing resistance against antimi-crobial drugs in bacteria. Close human contact might have a higher chance of being transmitted to humans from sheep if the sheep population is a potential reservoir of zoonotic pathogens such as shiga toxin-producing Escherichia coli (E. coli) (STEC). Therefore, this study aimed to exam-ine the sheep population in rural Bangladesh for antimicrobial resistant STEC. We screened 200 faecal samples collected from sheep in three Upazila from the Chattogram district. Phenotypical-ly positive E. coli isolates were examined for two shiga toxin-producing genes – stx1 and stx2. PCR positive STEC isolates were investigated for the presence of antimicrobial resistance genes- blaTEM, sul1 and sul2. In total, 123 of the 200 tested samples were confirmed positive E. coli by cul-tured based methods. PCR results show 17(13.8%) E. coli isolates harboured ≥ one virulent gene (stx1 or/and stx2) of STEC. Six of the tested STEC isolates exhibited blaTEM gene; eight STEC isolates had sul1 gene, and sul2 gene was detected in ten STEC isolates. To our knowledge, this study is the first to reveal a significant proportion of STEC isolated from sheep in rural Bangla-desh harbouring antimicrobial resistance genes.

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

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

Leucine-rich repeat receptor-like kinases (LRR-RLKs) have been reported to play important roles in plant growth, development and stress responses. However, no comprehensive analysis of this family has been performed in Gossypium, which are important economic crop and suffer various stresses in growth and development. Here we conducted a comprehensive analysis of LRR-RLK family in four Gossypium species (G. arboreum, G. barbadense, G. hirsutum and G. raimondii). A total of 1641 LRR-RLK genes were identified in the four Gossypium species involved in our study. Maximum-likelihood phylogenetic tree revealed that all the LRR-RLK genes were divided into 21 subgroups. Exon-intron organization structure of LRR-RLK genes kept relative conserved in subfamilies and between Arabidopsis and Gossypium. Subfamilies XI and XII were found dramatically expanded in Gossypium. Tandem duplication acted as an important mechanism in expansion of Gossypium LRR-RLK gene family. Function analysis suggested that plant hormone signaling and plant-pathogen interaction pathway were enriched in Gossypium LRR-RLK genes. Promoters analysis and expression profiles analysis revealed that Gossypium LRR-RLK genes were extensively regulated by TFs, phytohormone and various environmental stimuli, and play key roles in stress defense and diverse development processes. Our study provided valuable information for further function study of Gossypium LRR-RLK genes.

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

Reconstructing the Tree of Life remains a central goal in biology. Early methods, relying on small numbers of morphological or genetic characters, often yielded conflicting evolutionary histories, undermining confidence in the results. Investigations based on phylogenomics, which use hundreds to thousands of loci for phylogenetic inquiry, have provided a clearer picture of life's history, but certain branches remain problematic. To resolve difficult nodes on the Tree of Life, two recent studies tested the utility of synteny, the conserved collinearity of orthologous genetic loci in two or more organisms, for phylogenetics. Synteny exhibits compelling phylogenomic potential while also raising new challenges. We identify and discuss specific opportunities and challenges that bear on the value of synteny data and other rare genomic changes for phylogenomic studies. Synteny-based analyses of highly contiguous genome assemblies mark a new chapter in the phylogenomic era and the quest to reconstruct the Tree of Life.

Hereditary cardiomyopathies (CMPs), including Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Dilated Cardiomyopathy (DCM), and Hypertrophic Cardiomyopathy (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity and mortality and are often driven by genetic factors. Recent advances in Next-Generation Sequencing (NGS) technology have enabled the identification of rare variants in both well-established and minor genes associated to CMPs. Nowadays, a set of core genes is included in diagnostic panels for ARVC, DCM, HCM. On the other hand, despite their lesser-known status, variants in the minor genes may contribute to disease mechanisms and influence prognosis. This review evaluates the current evidence supporting the involvement of the minor genes in CMPs, considering their potential pathogenicity and clinical significance. A comprehensive analysis of databases such as ClinGen, ClinVar, and GeneReviews, along with recent literature and diagnostic guidelines, provides a thorough overview of the genetic landscape of minor genes in CMPs and offers insights for future research and translation to clinical practice. Given the increasing knowledge on these less-understood genetic factors, future studies are essential to clearly assess their roles, ultimately leading to improved diagnostic precision and therapeutic strategies in hereditary CMPs.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival related genes (SRBs) using the gene expression dataset of Cavalli et al. (2017) and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1), which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype with 93% deletion of 17p and 98% copy gain of 17q. Pathway analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provide a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosome 6 and 17 warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

The resistance of Candida spp to fluconazole is a serious problem; Therefore, it must be investigated to expand the understanding of the phenomenon with a view to its clinical applicability. The aim was to evaluate the expression of ERG3, ERG11, CDR1, and SNQ2 genes involving computational analysis. Relative expression was quantified by RT-qPCR. Metrics were obtained by molecular docking and through Fisher's discriminant functions, a predictive classification against susceptibility to fluconazole was performed. The expression of ERG3, CDR1, and SNQ2 genes was higher in resistant strains than in dose-dependent sensitive strains. The gene with the highest expression in strains exposed to fluconazole was CDR1 and, in both resistant and dose-dependent sensitive strains exposed to fluconazole, the ERG11 gene had lower expression. The molecular docking model generated lower median fluconazole-ERG11 contacts than the median fluconazole-ERG3, -CDR1, and -SNQ2 contacts. The predicted classification through the multivariate model for fluconazole sensitivity obtained an accuracy of 73.5%. Resistant strains had a significant expression of CDR1, SNQ2 and ERG3 genes, compared to a comparatively low expression of ERG11. Molecular analysis identified a low affinity between fluconazole and its drug target, which may explain a lower intrinsic susceptibility of the fungus.

Background. The treatment for patients with high-grade gliomas includes radiation therapy and temozolomide. However, some patients do not respond to temozolomide because they have a methylation reversal mechanism through the enzyme O6-methylguanine-DNA-methyltransferase. This biomarker has been used as a prognostic factor in patients receiving treatment with temozolomide. However, not all patients respond in the same way, which suggests the existence of other genes involved in resistance to temozolomide. Materials and Methods. A group of 31 patients with high-grade gliomas was recruited and were clinically, image pattern, and pathologically characterized. The sequencing of 324 genes related to different types of cancer was performed to detect mutations. Subsequently, a statistical analysis was conducted to determine the mutated genes that were most related to resistance to treatment. Results. The genes related to the second relapse of patients with high-grade glioma after the use of temozolomide according to Stupp protocol and metronomic dose were PIK3C2B, KIT, ERBB3, and MLH1. Conclusions. Considering the results obtained, we suggest that the mutations in the four genes and the methylation of the gene promoter that codes for MGMT protein could be related to the clinical evolution of patients with high-grade gliomas and its response to treatment with temozolomide.

Acquired immunodeficiency syndrome (AIDS) has transitioned from a progressive, fatal disease to a chronic, manageable disease thanks to better defining of antiretroviral therapy, hence contributing to increased life expectancy. In parallel, a growing number of subjects without overt clinical signs of disease but living with chronic HIV infection (people living with HIV, PLWH) are experiencing early cardiovascular disease worldwide. However, a progressive increase in the prevalence of multiple comorbid diseases has been reported as these patients age, including cardiovascular disease (CVD). Cardiovascular mortality can be either directly related to the viral infection, a progressive reduction of response to the antiretroviral therapy, chronic inflammation or lifestyle-related. Cardiovascular ageing represents a relevant issue in the management of HIV-infected patients. Although the exact pathophysiological mechanism that leads PLWH to develop cardiovascular disease is not entirely understood, there is substantial evidence that they accumulate age-related conditions earlier than the general population. Furthermore, since the proportion of PLWH growing older than 50 years has progressively increased, this results in a complex interaction between disease-related pathophysiology and the exposition of a growing burden of cardiovascular risk factors. For this reason, we performed a systematic review of the genes most frequently associated with ageing in HIV-infected subjects, followed by a bioinformatic analysis to explore the biological impact of the genes related to ageing.

The soil-borne pathogens, particularly Fusarium oxysporum f. sp. niveum (FON) and southern root-knot nematode (RKN, Meloidogyne incognita) are the major threat to watermelon production in the south-eastern United States. The role of soil micronutrients on induced resistance (IR) to plant diseases is well-documented in soil-based mediums. However, soil-based mediums limit the determination of the role(s) of individual micronutrients in IR. In this manuscript, we utilized hydroponics to assess the effect of controlled application of micronutrient, including iron (Fe), manganese (Mn), and zinc (Zn) on the expression of some IR genes (PR1, PR5, and NPR1 from salicylic acid (SA) pathway, and VSP, PDF, and LOX genes from jasmonic acid (JA) pathway) in watermelon seedlings upon inoculation with either FON or RKN or both. Plants were treated with higher (3X) or lower (0.5X) concentrations of micronutrients in Steiner solution (X= standard dose of micronutrient) for 7 days in a hydroponics system under greenhouse conditions. A subset of micronutrient-treated plants was inoculated (on the 8th day of micronutrient application) with FON and RKN (single and mixed). The expression of the IR genes in treated and control samples were evaluated using qRT-PCR. Although, significant phenotypic differences were not observed with respect to the severity of wilt symptoms or RKN galling with any of the micro-nutrient treatments within the 30 day-experimental-period, differences in the induction of IR genes were observed. However, the level of gene expression varied with sampling period, type and concentration of micro-nutrients ap-plied, and pathogen-inoculation. In the absence of pathogens, no significant changes were observed in the expression level of IR genes on 7th day of micronutrient treatment. However, pathogen inoculation affected the expression levels of the IR genes at 3-day post-inoculation. In FON inoculated plants, PDF was upregulated in high Fe treatment, whereas in RKN inoculated plants, low Mn treatment resulted in up-regulation of VSP. In the case of mixed inoculation with FON and RKN, the plants with low Zn treatment resulted in the upregulation of PR1. These observations suggest that the type and concentration of micronutrients in watermelon may potentially induce systemic resistance against FON and RKN through SA and JA pathways.

This paper illustrates an experimental activity for the closed-loop position control of an actuator made using shape memory alloy (SMA) wire. A solution with the self-sensing effect was implemented to miniaturize the systems, i.e., without external sensors. A proportional control algorithm was initially used, demonstrating the idea's feasibility: the wire can behave simultaneously as an actuator and sensor. An experimental investigation was subsequently conducted for the optimization of the developed actuator. As for the material, a Flexinol wire, Ni-Ti alloy, with a diameter of 0.150 mm and a length of 200 mm, was used. Preliminarily, a characterization of the SMA wire at constant and variable loads was carried out: the characteristics detected are elongation vs. electric current and elongation vs. electrical resistance. The control system is PC-based with a data acquisition card (DAQ). A drive board has been designed and built to read the wire's electrical resistance and power it by pulse width modulation (PWM). A notable result is that the actuator works with good precision and in dynamic conditions, even when it is called to support a load up to 65% different from that for which the electrical resistance-length correlation has previously been experimentally obtained, on which the control is based. This opens up the possibility of using the actuator in a counteracting configuration with a spring, which makes hardware implementation and control management simple.

The amino acid proline accumulates in plants during abiotic stresses such as drought and salinity and is considered a reliable marker of environmental stress. While its accumulation is well established, its precise role in stress tolerance and its underlying molecular mechanism remain less clear. To address these issues, we performed a meta-analysis - a robust statistical technique that synthesizes results from multiple independent studies while accounting for experimental differences. We focused on 16 physiological and morphological parameters affected by drought and salt stress in transgenic plants expressing proline metabolic genes. For each parameter, we calculated the effect size as the response ratio (RR), which represents the logarithm of the mean value in the transgenic group over the mean value of the control group (lnRR). Under stress, most parameters exhibited significantly higher response ratios in the transgenic group, confirming the beneficial effects of proline during drought and salt stress. Surprisingly, under non-stressed conditions, most stress markers showed no significant differences between transgenic and non-transgenic plants, despite elevated proline levels in the former. These results suggest that the benefits of proline may be related to proline catabolism or may only become apparent during stress, possibly due to interactions with reactive oxygen species (ROS), which accumulate predominantly under stress conditions.

Conventional farming relies on large-scale, intensive crop production using mechanical tillage and synthetic inputs like chemical fertilizers and pesticides, which, despite being economically beneficial, can be environmentally destructive, whereas organic cropping system offers a more sustainable alternative with less harmful environmental impact. But is organic system more beneficial for soil health than conventional? In this study, we focused on evaluating the functional potential of soil for the conversion of carbon, nitrogen, phosphorus, and sulfur, as well as measuring the actual activity of enzymes involved in these cycles. We used Chernozem soil samples from fields that were managed using organic (OCS) and conventional (CCS) methods as the objects of our study. Another objective of the study was to compare two methods: profiling of functional genes of the microbial community and measurement of actual enzyme activity. The comparison of OCS versus CCS indicates that functional gene profiling and enzymatic activity measurements similarly capture qualitative differences between these systems, but diverge in how they assess quantitative differences. A combination of these two methods for assessing soil conditions appears to be promising. Overall, the study demonstrated that the agronomic practices used in the conventional cropping system not only preserved the functional properties of the soil microbiome but also significantly enhanced its microbiological activity for nutrient bioconversion compared to the organic cropping system. However, the question remains as to how long the conventional system can sustain its high potential.

Obesity, type 2 diabetes, and different forms of cancers are among the leading human diseases and highly complex in terms of diagnostic and therapeutic approaches. Diabetes and cancer are among the most frequent and complex diseases and based on epidemiological evidence and study it can be concluded that the patients suffering from diabetes are considered to be significantly at higher risk for a number of cancer types. Both these diseases are among the highly complex and heterogeneous in nature. There are a number of evidences which support the hypothesis that these diseases interlinked and obesity may aggravate the risk(s) of both these diseases type 2 diabetes and different types of cancers. Multi-level unwanted alterations such as (epi-)genetic alterations, changes at the transcriptional level, and altered signaling pathways (receptor, cytoplasmic, and nuclear level) are the major source which promotes a number of complex diseases and such heterogeneous level of complexities are considered as the major barrier in the development of therapeutic. With so many known challenges, it is critical to understand the relationships and the common shared causes between type 2 diabetes and cancer which is difficult to unravel and understand. Furthermore, the real complexity arises during diagnosis from contended corroborations that specific drug(s) (individually or in combination) during diagnosis process of type 2 diabetes may increase or decrease the cancer risk or affect cancer prognosis. In this review article, we have presented the recent and most updated evidences from the studies where the origin, biological background, correlation between them have been presented or proved. Furthermore, we have summarized the methodological challenges and tasks that are frequently encountered. we have also outlined the physiological links between type 2 diabetes and cancers. Finally, we have presented and summarized the outline of the hallmarks for both these diseases diabetes and cancer.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

Bacterial resistance to antibiotics is a public health menace that needs urgent efforts to mitigate and forestall their transmission in the general environment. Plasmid-mediated metallo beta-lactamase (MBL) gives bacteria an exceptional ability to transmit resistance genes. This study investigated plasmid-mediated resistance in MBL P. aeruginosa isolates from poultry food chain settings. Cloacal swab samples (n=120) were bacteriologically analyzed for the isolation of P. aeruginosa isolates. Susceptibility studies were performed by the CLSI guideline using selected antibiotics. MBL was phenotypically detected using modified Hodges test, and confirmed using PCR technique. Plasmid curing studies detected the presence of plasmids in the isolates. P. aeruginosa isolates (n=48) showed high levels of reduced susceptibility to cefoxitin (93.8%), imipenem (81.3%), gentamicin (85.4%), amikacin (85.4%), nitrofurantoin (83.3%), ofloxacin (72.9%) and cefotaxime (77.1%). MBL was phenotypically detected in 7 (14%) isolates of P. aeruginosa. The presence of blaIMP-1 and blaIMP-2 MBL genes in P. aeruginosa (n=5) isolates was confirmed by PCR. The PCR did not detect blaVIM-1 and blaVIM-2 MBL genes. The P. aeruginosa isolates were multidrug resistant, with about 50% of the isolates showing multidrug resistance (MDR) to the antibiotics. The genes for MDR in the P. aeruginosa isolates were borne on plasmids, indicating a high possibility of community transmission of MBL resistance genes. Finally, the P. aeruginosa isolates from poultry food chain milieus are multidrug resistant, produce MBL, and harbour their resistance genes on plasmids. Since many antibiotic resistance genes in bacteria are associated with mobile genetic elements (MGEs) like plasmids, it is important to step up actions to mitigate incessant use of antibiotics in poultry and other agricultural practices in Nigeria in order to diminish the evolution and spread of plasmid-mediated resistance which is capable of initiating community acquired infections that may prove difficult to treat in our hospitals with the available antibiotics.

In the crustacean immune system, leucine-rich repeat (LRR) is one of the major structures for recognizing pathogen-associated molecular patterns (PAMPs). LRR domain-containing proteins belong to the LRR family, which is a large group of proteins with more than 6000 genes in the database. They are involved in very diverse physiological functions mainly by interacting with other proteins. In a previous study, the LvLRRm, a transmembrane protein containing only LRR domain, was identified in the white leg shrimp, Litopenaeus vannamei. Its versatile role in performing multiple immunomodulation activities has been reported. However, there is still a lack of research on its efficient function at the protein level. To investigate its interactions with other proteins, we applied a convenient method called ‘Hybrid LRR technique’ to produce a recombinant LvLRRm. The LvLRRm and hagfish’s variable lymphocyte receptors (VLRs) fragments were fused to the conserved LxxLxLxxN motif while retaining the β-strand. In addition, we established interactions between hybrid-proteins and flagellin of Salmonella by performing surface plasmon resonance (SPR) analysis. The designed hybrid proteins showed potential for universal applications without losing protein functions.

The application of antimicrobials in aquaculture primarily aims to prevent and treat bacterial infections in fish. Inappropriate use of antimicrobials in fish farming may result in the emergence of zoonotic antibiotic-resistant bacteria and subsequent transmission of resistant strains to humans via food consumption. From recently, AMR emerged as a significant public health concern in the aquaculture ecosystem and fisheries. The aquatic environment serves as a potential reservoir for resistant bacteria, with aquaculture practices providing an ideal breeding ground for AMR due to the excessive use of antimicrobials to prevent and treat diseases. The mutual inter-connection of intensive fish farming systems with terrestrial environments, food processing industry and human population creates pathways for the transmission of resistant bacteria, exacerbating the problem further. One Health concept, which recognizes the interconnectedness of human, animal and environmental health, enables a holistic approach to address the challenges posed by AMR. By understanding the evolution of such approach, the future of aquaculture, being the important source of a global animal protein supply, can be safeguarded. Risk mitigation strategies for AMR should be based on One Health concept to contribute to sustainable aquaculture practices that protect human and animal health, ensure food safety and protection of environment.

In agriculture, soil-borne fungal pathogens, especially Fusarium oxysporum strains, are posing a serious threat to efforts to achieve global food security. In the search for safer agrochemicals, silica nanoparticles (SiO2NPs) have recently been proposed as a new tool to alleviate pathogen damage including Fusarium wilt. Hollow mesoporous silica nanoparticles (HMSNs), a unique class of SiO2NPs, have been widely accepted as a desired pesticide carrier. However, their role in enhancing the disease resistance and the specific mechanism remain unknown. In this study, three sizes of HMSNs (19, 96 and 406 nm as HMSNs–19, HMSNs–96 and HMSNs–406, respectively) were synthesized and characterized to determine their effects on seed germination, seedling growth, and Fusarium oxysporum f. sp. phaseolus (FOP) suppression in cowpea roots by foliar spray using phenotypes, fresh biomass and disease progression as indicators. The results revealed that three HMSNs exhibited no adverse impacts on seed germination and tended to improve plant growth. Also, they exert their FOP suppression with a size- and concentration-dependent manner. HMSNs–406 possessed the best control effect at a concentration of 1000 mg/L showing an upto 40.00% decline in the disease severity. The Si(OH)4 control was also effective on FOP suppression at a lower concentration of 100 mg/L, whereas its higher concentrations exhibited obviously adverse impacts on FOP control, seed germination and plant growth. Moreover, we conformed that HMSNs posed their Fusarium wilt suppression in cowpea plant by activating SA (salicylic acid)-dependent SAR (systemic acquired resistance) responses rather than directly suppressing FOP. A higher level of SA content and elevated expression of its maker genes of PR-1 and PR-5 in HMSNs–406 treated cowpea roots provided substantial evidences of this mode of action. Other resistance-related genes, as well as defense-responsive enzymes, were also involved in the HMSNs-activated SAR pathway. Overall, for the first time, our results extended a new role of HMSNs as a potent elicitor to serve as a versatile alternative for plant disease protection of low cost, highly efficiency and sustainability.

Continuous technological progress places significant demands on the materials used in increasingly modern devices. An important parameter is often the long-term thermal resistance of the material. The use of heat-resistant polymer materials worked well in technologically advanced products. An economically justified direction in searching for new materials is the area of polymer nanocomposite materials. It is necessary to appropriately select both the polymer matrix and the nanofillers best able to demonstrate the synergistic effect. A promising area of exploration for such nanocomposites is the use of organosilicon polymers, which results from the unique properties of these polymers related to their structure. This review presents the results of the analysis of the most important literature reports regarding organosilicon polymer nanocomposites with increased thermal resistance. Particular attention was paid to modification methods of silicone nanocomposites focused on the increase of their thermal resistance related to the modification of siloxane molecular structure and by making nanocomposites using inorganic additives, carbon nanomaterials. Attention was also paid to such important issues as the influence of the dispersion of additives in the polymer matrix on the thermal resistance of silicone nanocomposites and the possibility of modifying the polymer matrix and permanently introducing nanofillers thanks to the presence of various reactive groups. The thermal stability mechanism of these nanocomposites was also analysed.

Lily tepals have a short lifespan. Once the tepals senesce, the ornamental value of the flower is lost. Some cultivars have attractive purple ovaries and fruits which greatly enhance the ornamental value of Asiatic hybrid lilies. However, little is known about the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries. To investigate the transcriptional network that governs purple ovary coloration in Asiatic hybrid lilies, we obtained transcriptome data from green ovaries (S1) and purple ovaries (S2) of Asiatic ‘Tiny Padhye’. Comparative transcriptome analysis revealed 4228 differentially expressed genes. Differential expression analysis revealed that nine unigenes including four CHS genes, one CHI gene, one F3H gene, one F3′H gene, one DFR gene, and one UFGT gene were significantly up-regulated in purple ovaries. One MYB gene, LhMYB12-Lat, was identified as a key transcription factor determining the distribution of anthocyanins in Asiatic hybrid lily ovaries. Further qPCR results showed unigenes related to anthocyanin biosynthesis were highly expressed in purple ovaries of Asiatic ‘Tiny Padhye’ at stages 2 and 3, while they showed an extremely low level of expression in ovaries of Asiatic ‘Yellow Pixels’ during all developmental stages. In addition, shading treatment significantly decreased pigment accumulation by suppressing the expression of several unigenes related to anthocyanin biosynthesis in ovaries of Asiatic ‘Tiny Padhye’. These results could further our understanding of the molecular mechanisms of anthocyanin biosynthesis in Asiatic hybrid lily ovaries.

Fungal plant diseases are a major threat to food security worldwide. Current efforts to identify and list loci involved in different biological processes are more complicated than originally thought, even when complete genome assemblies are available. Despite numerous experimental and computational efforts to characterize gene functions in plants, about ~ 40% of protein-coding genes in the model plant A. thaliana are still not categorized in the Gene Ontology Biological Process (BP) annotation. In non-model organisms, such as sunflower (Helianthus annuus), the number of BP term annotation is far fewer, ~22%. In the current study we performed gene co-expression network analysis using eight terabytes of public transcriptome datasets and performed expression-based functional prediction to categorize and identify loci involved in the response to fungal pathogens. We were able to construct a reference gene network of healthy green tissue (GreenGCN) and a gene network of healthy and stressed root tissues (RootGCN). Both networks achieved robust high quality scores on the metrics of guilt-by-association and selective constraints versus gene connectivity. We were able to identify eight modules enriched in defense functions, of which, two out of the three modules in the RootGCN were also conserved in the GreenGCN, suggesting similar defense-related expression patterns. We identified 16 WRKY genes involved in defense related functions and 65 previously uncharacterized loci now linked to defense response. In addition, we identified and classified 122 loci previously identified within QTL or near candidate loci reported in GWAS studies of disease resistance in sunflower linked to defense response. In all, we have implemented a valuable strategy to better describe genes within specific biological processes.

Nature-based solutions (NbS) rapidly develop globally to address societal challenges and provide human well-being and biodiversity. Watershed restoration plays an essential role in enhancing the ecological and socio-economic benefits of the region. The design and implementation of watershed restoration projects play a crucial role in their effectiveness, and NbS has been applied as a concept in ecosystem-related projects. This paper provides an idea to evaluate the design or implementation of watershed restoration projects based on the eight criteria proposed by the IUCN Global Standard for Nature-Based Solutions and to adjust the projects based on the evaluation results. The aim is to standardize the implementation process of watershed restoration projects to achieve more significant benefits and practically apply the concept of NbS in watershed restoration. implementation scheme of the Shan-Shui Initiative in the Jiulong River Watershed and concludes that the method is feasible in evaluating and improving the design and implementation scheme of ecological restoration projects in the actual basin. According to the assessment results, the degree of matching based on NbS for the implementation scheme of the Jiulong River Watershed Shan-Shui Initiative is 73%, which meets the criteria of NbS but needs to be improved in terms of monitoring and assessment, synergistic management, and benefit trade-offs.

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary the safety evaluations including antibiotic resistance for the use as starters. In this research, we investigated the antibiotics resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter, against ten different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study.

Culex quinquefasciatus is an important target for vector control because of its ability to transmit pathogens that cause disease. Most populations are resistant to pyrethroids and often to organophosphates, the two most common classes of active ingredients used by public health agencies. A knockdown resistance (kdr) mutation, resulting in a change from a leucine to phenylalanine in the voltage gated sodium channel, is one mechanism contributing to the pyrethroid resistant phenotype. Enzymatic resistance has also been shown to play a very important role. Recent studies have shown strong resistance in populations even when kdr is relatively low which indicates factors other than kdr may be larger contributors to resistance. In this study, we examined on a statewide scale (over 70 populations), the strength of the correlation between resistance in the CDC bottle bioassay and the kdr genotypes and allele frequencies. Spearman correlation analysis showed only moderate (-0.51) and weak (-0.29) correlation between the kdr genotype and permethrin and deltamethrin respectively. The frequency of the kdr allele was an even weaker correlate. These results indicate, in contrast to Aedes aegypti, assessing kdr in populations of Culex quinquefasciatus is not a good surrogate for phenotypic resistance testing.

Psoriasis is a multifactorial, chronic, and inflammatory disease that severely impacts patients’ quality of life. The disease is caused by genetic irregularities affected by the epigenetic and environmental factors. Some of these factors may include the seasonal changes, such as solar radiation, air pollution and humidity, and changes in circadian rhythm, especially in the temporal and polar zones. Thus, some psoriasis patients report seasonal variability of symptoms. Through a comprehensive review, we aim to delve deeper into the intricate interplay between seasonality, environmental factors, and the genetic and epigenetic landscape of psoriasis. By elucidating these complex relationships, we strive to provide insights that may inform targeted interventions and personalized management strategies for individuals living with psoriasis.

Long COVID, also referred to as post-COVID-19 condition, describes the lingering after-effects of COVID-19 infection. This complex syndrome encompasses a range of symptoms affecting physical well-being, cognitive function, and mental health. The widespread impact of long COVID extends beyond individual sufferers, placing significant strain on healthcare systems and causing far-reaching socioeconomic consequences. The scale of this multifaceted health crisis is unparalleled in recent history, affecting millions globally and challenging our understanding of post-viral conditions. This study aimed to explore the possibility of targeting G protein-coupled receptors (GPCRs) signaling pathway-related genes as therapeutics for long COVID using computational analysis. Targeting GPCRs and their signaling pathways holds significant promise for long COVID therapeutics, as these receptors are involved in crucial physiological processes including immune regulation, inflammation control, and neurotransmission. All of these are implicated in the diverse and persistent symptoms of long COVID, potentially offering a versatile approach to addressing multiple aspects of the condition simultaneously. This study identified 21 genes associated with GPCRs for further exploration as potential targets. Notably, GPCR genes such as HRAS, KRAS, GNAQ, and GNA11 were determined to be possible therapeutic targets for the pathophysiological mechanisms of long COVID. FDA-approved drugs targeting these genes were identified, including Binimetinib, Cabozantinib, Selumetinib, Panitumumab, Cetuximab, Adagrasib, Tipifarnib, and Sotorasib. Additionally, Naltrexone and Tipifarnib have emerged as potential new treatment options for long COVID. SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport, contributing to the pathophysiology of pulmonary edema in patients with COVID-19. Further research is required to translate the findings into the development of therapeutics and to investigate the relationship between viral infection and GPCR signalling.

Salt stress is a major limiting factor for alfalfa yield due to its relatively low salt tolerance. High soil salinity adversely impacts alfalfa growth and development, leading to reduced yield. Melatonin (MT) is known to play a significant role in enhancing plant resistance to abiotic stresses. However, the mechanisms underlying melatonin-mediated abiotic stress responses, particularly salt stress, are not well understood. To address this gap, we conducted a study focusing on germinating alfalfa seeds under salt stress. Physiological indexes and transcriptomics analyses were carried out on the germinated seeds to investigate the effects of melatonin on alfalfa seedlings under salt stress conditions. Our results revealed that the application of melatonin led to an increase in shoot length and fresh weight of alfalfa seedlings under salt stress. Moreover, key physiological indexes such as peroxidase (POD) activity and glutathione (GSH) content were enhanced, while levels of malondialdehyde and superoxide anions decreased. Transcriptomic analysis identified a total of 2,131 differentially expressed genes in the salt-treated group, with 726 up-regulated and 1,405 down-regulated genes, while the MT-treated group showed 2896 differentially expressed genes, of which 1,097 were up-regulated and 1,799 were down-regulated. Further, KEGG enrichment analysis highlighted the enrichment of differentially expressed genes in pathways including flavonoid biosynthesis, ABC transporter, glutathione metabolism, and the MAPK signaling pathway, with these pathways more significantly enriched in the MT-treated group. These findings collectively suggest that melatonin plays a crucial role in alfalfa's response to salt stress and offer new insights into the genomic mechanisms underlying melatonin-mediated salt tolerance in alfalfa.

Nose mask is a fomite and its usage was mandatory during the COVID-19 outbreak. Its effectiveness has been established; however, as a fomite, it can harbor opportunistic respiratory pathogens such as Streptococcus spp., which could complicate COVID-19 infections. This study profiled Streptococcus species resident on nose masks obtained from consenting participants. Phenotypic assays and 16S rRNA sequencing were used to identify Streptococcus spp. resident on the interior and exterior of 100 nose masks analyzed. Antibiotic resistance (AMR) was determined with disc diffusion and broth microdilution assays. AMR and virulence makers were profiled with primer-specific PCR amplification. 23% of the analyzed samples had Streptococcus isolates. The isolates were highly resistant to the antimicrobials, including conventional, last-resort antibiotics, disinfectants and antiseptics. All the isolates are multidrug resistant with 80-100% levels of AMR to the 16 antibiotics tested with a Multiple-Antibiotic Resistance index greater than 0.2, indicative of potential pathogens. The isolates harbored tetB, ermB, pbp2B, pbp2b1 (resistance) and lytA, lytA1, ply1, cbpA, lytA, pavA (virulence) markers, which might constitute a serious public health risk. Overall, the study emphasizes the need to assess mask usage and the risks associated with opportunistic pathogens that are resident on frequently used nose masks in the COVID-19 era.

The sexual reproduction of ascomycetes is controlled by the mating-type(MAT) locus. (Pseudo)homothallic reproduction has been hypothesized based on genetic data from Hirsutella sinensis (Genotype #1 of Ophiocordyceps sinensis). In this study, the differential occurrence of the mating-type genes in the MAT1-1 and MAT1-2 idiomorphs, which constitute the genetic control of O. sinensis reproduction, was analyzed in 237 strains and 5 genomes of H. sinensis. The mating-type genes were differentially transcribed in H. sinensis Strain L0106, and the MAT1-2-1 transcript in H. sinensis Strain 1229 was alternatively spliced, with an unspliced intron I containing stop codons; these findings constitute O. sinensis reproduction controls at the transcriptional and coupled transcriptional-translational levels. The occurrence of the mating-type genes and a-/α-pheromone receptor genes differed among the 5 H. sinensis genomes. The differential occurrence and transcription of these genes are inconsistent with self-fertilization under (pseudo)homothallism but suggest self-sterility of H. sinensis, which therefore needs a mating partner to achieve sexual outcrossing under heterothallism or hybridization. Consistent occurrence and transcription of the mating-type genes of both the MAT1-1 and MAT1-2 idiomorphs have been reported in natural and cultivated Cordyceps sinensis, but these findings are insufficient to determine the reproduction mode(s) because of the co-occurrence of >90 fungal species and multiple genomically independent genotypes of O. sinensis. The mutant MAT1-1-1 and α-pheromone receptor transcripts in natural C. sinensis result in the N-terminus or middle-truncated proteins, with changes in hydrophobicity and secondary structures of the proteins, suggesting heterogeneous fungal source(s) of the proteins and hybridization reproduction.

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

Indoor residual spray (IRS), mainly employing pyrethroid insecticides, is the most common intervention to prevent malaria transmission in many regions of Latin America; the use of long-lasting insecticidal nets (LLINs) has been more limited. Knockdown resistance (kdr) is a well-characterized target-site resistance mechanism associated with pyrethroid and DDT resistance. Most mutations detected in acetylcholinesterase-1 (Ace-1) and voltage-gated sodium channel (VGSC) genes are non-synonymous, resulting in a change of amino acid leading to non-binding of the insecticide. In the present study, we analyzed target-site resistance in Nyssorhynchus darlingi, the primary malaria vector in the Amazon, in multiple malaria endemic localities. We screened 988 wild-caught specimens of Ny. darlingi from three localities in Amazonian Peru and four in Amazonian Brazil. Collections were conducted between 2014-2021. Criteria were Amazonian localities with a recent history as malaria hotspots, primary transmission by Ny. darlingi and the use of both IRS and LLINs as interventions. Fragments of Ace-1 (456 bp) and VGSC (228 bp) were amplified, sequenced and aligned with Ny. darlingi sequences available in GenBank. We detected only synonymous mutations in the frequently reported Ace-1 codon 280 known to confer resistance to organophosphates and carbamates, but detected three non-synonymous mutations in other regions of the gene. Similarly, no mutations linked to insecticide resistance were detected in the frequently reported codon (995) at the S6 segment of domain II of VGSC. The lack of genotypic detection of IR mutations by sequencing the Ace-1 and VGSC genes from multiple Ny. darlingi populations in Brazil and Peru could be associated with low-intensity resistance, or possibly the main resistance mechanism is metabolic.

The objective of this study was to investigate the transcriptomic profiling of differentially ex-pressed genes between a commercial layer breed and an indigenous Indian breed. RNA was ex-tracted from NDV-infected and uninfected embryo lung tissue samples of Aseel, Kadaknath, and White Leghorn chickens. RNA-Seq was performed, and reads were aligned to the chicken refer-ence genome (Galgal7). A total of 594 genes were significantly differentially expressed, with 264 upregulated and 330 downregulated in infected embryos. Highly overexpressed genes in infect-ed conditions included C8A, FGG, PIT54, FETUB, APOC3, FGA, SPIA1, AvBD13, APOH, AMBP, TTR, PLA2G12B. Additionally, 29 novel transcripts and 20 lncRNAs were upregulated. White Leghorn embryos showed distinct expression patterns for CAV1 and GATA3, while Kadaknath healthy embryos had higher levels of CYTB, HBBA, ND4, ND4L, and ND5, indicating breed uniqueness. The analysis revealed significant gene involvement through Gene Ontology and KEGG pathways, highlighting alterations in gene expression related to immune function, me-tabolism, cell cycle, nucleic acid processes, and mitochondrial activity due to NDV infection. ALDOB, PRPS2, XDH, DCK2, and TK1 genes, which were involved in several metabolic path-ways, clearly displayed an altered expression pattern in the infected embryo. Additionally, ALB, TLR4, TLR2, TLR21, IL1R2, IL22RA2, HSP90AA, HSPB9(p60), and HSPB8 were significantly up-regulated in infected lung samples, while CXCR4, CXCL14, GATA3, IL17REL, and IL22RA1 were downregulated. Notably, higher expression of HSPs in Kadaknath suggests heat tolerance. This research provides insights into the genetic differences between commercial and local breeds and reveals the impact of NDV infection on metabolic processes, potentially identifying candidate genes for breed improvement.

Improvement of hydrophysical properties and corrosion resistance of self-compacting concrete to the effects of alternate freezing-thawing and aggressive soils of southern and central Kazakhstan is of interest to a wide range of researchers from the side of practical application of the obtained results in construction practice. It is proposed to form a spatially reinforced fine crystalline structure of cement matrix with maximum dense packing by using a complex modifier (Hyperplasticiser + Polymer + Microsilica + Fibro fibers) in the composition of self-compacting concretes (SCC). The introduction of the calculated amount of the above additives increases the operational reliability of the current SCC compositions, increasing the water resistance to W16, frost resistance to F=500, increasing the compressive strength by 20%, reducing the mass loss of samples during corrosion leaching to 50%. It has been experimentally established that the proposed addition of complex modifier (Hyperplasticiser + Polymer + Microsilica + Fiber fibers) to the SCC composition allows obtaining self-compacting concrete of high quality with improved performance characteristics (compressive strength, water resistance, frost resistance and corrosion resistance). Studies have shown that the complex modifier-modified SCC compositions have a high degree of resistance in aggressive environments and leaching corrosion. Based on the results of the conducted tests, it is possible to recommend the obtained SCC compositions for production of building products working in the zone of alternating freezing-thawing and aggressive soils.

Rice prolamins are categorized into three groups by molecular size (10, 13, or 16 kDa), while the 13 kDa prolamins are assigned to four subgroups (Pro13a-I, Pro13a-II, Pro13b-I, and Pro13b-II) based on cysteine residue content. Here, we generated four knockout strains of rice using CRISPR-Cas9, each of which demonstrated selectively reduced expression of specific subgroups of the 13 kDa prolamins. These four mutant rice lines also demonstrated compensatory expression of glutelins and non-targeted prolamins, which resulted in low grain weight, altered starch content and atypically-shaped starch granules and protein bodies. Transcriptome analysis identified 746 transcripts that were differentially expressed in the mutant rice lines during development. These transcripts played roles primarily in RNA processing, protein synthesis, stress response, and transport. After selective suppression/knockout of genes in the Pro13a-I subgroup, compensatory upregulation of genes in the Pro13a-II and Pro13b-I/II subgroups was observed. Compensatory expression of 9 ER stress and 17 transcription factor genes was also observed in mutant rice in which expression of 13 kDa prolamin genes was suppressed. Our results provide valuable insight into the regulatory mechanisms underlying rice seed development and the specific roles played by 13 kDa rice prolamins and their target genes.

Rice, as a staple crop feeding billions, faces constant threats from various diseases jeopardizing global food security. Precise understanding of disease resistance mechanisms is crucial for developing resilient rice varieties. Traditional genetic mapping methods, such as QTL mapping, provide valuable insights into the genetic basis of diseases. However, the complex nature of rice diseases demands a holistic approach to gain accurate knowledge of it. Omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, enable a comprehensive analysis of biological molecules, uncovering intricate molecular interactions within the rice plant. Integration of various mapping techniques using multi-omics data has revolutionized our understanding of rice disease resistance. By overlaying genetic maps with high-throughput omics datasets, researchers can pinpoint specific genes, proteins, or metabolites associated with disease resistance. This integration enhances the precision of disease-related biomarkers with better understanding of their functional roles in disease resistance. Improvement of rice breeding for disease resistance through this integration represents a significant stride in agricultural science because better understanding of the molecular intricacies and interactions underlying disease resistance architecture leads to more precise and efficient development of resilient and productive rice varieties. In this review, we explore how the integration of mapping and omics data can give a transformative impact on rice breeding for enhancing disease resistance.

Autoimmune blistering diseases represent a group of chronic severe, disabling, potentially fatal disorders of the skin and/or mucous membranes primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality, a profound negative impact on the patient’s quality of life and impose a considerable economic burden. Rituximab, an anti CD-20 monoclonal antibody represents the first line of therapy for pemphigus, regardless of its severity as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab sooner or later. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory pemphigus cases are mandatory.

The study of the pathogenesis of febrile seizures and their consequences frequently necessitates gene expression analysis. The primary methodology employed for such analysis is reverse transcription with quantitative polymerase chain reaction (RT-qPCR). To guarantee the accuracy of data obtained by RT-qPCR, it is crucial to utilize stably expressed reference genes. The objective of this study was to identify the most suitable reference genes for use in the analysis of mRNA production in various brain regions of rats following prolonged neonatal febrile seizures. The expression stability of eight housekeeping genes was evaluated using the online tool RefFinder in the dorsal and ventral hippocampal regions and in the temporal and medial prefrontal cortex of the brain. The Ppia gene exhibited the greatest stability of expression. Conversely, the genes with the least stable expression level are Actb and Ywhaz; thus, it is not recommended to use them for normalization in a febrile seizure model. Additionally, the majority of housekeeping genes demonstrate age-related, region-specific fluctuations. Therefore, it is crucial to employ the appropriate housekeeping genes for each brain structure under investigation when examining the expression dynamics of genes of interest in a febrile seizure model.

The increasing diffusion of antimicrobial resistance represents one of the major public health problems worldwide. In the last years, novel antimicrobial molecules have been developed to contrast the emergence of antimicrobial resistance and to provide a valuable therapeutic options against multi drug-resistant (MDR) GNB microorganisms. A new siderophore cephalosporin, Cefiderocol, represents a novel valuable antimicrobial drug for the treatment of infections caused by MDR-GNB. The mechanism of cefiderocol to penetrate trough the outer membrane of bacterial cell with a particular mechanism defined at “Trojan horse” render this molecule unique and immune against the different strategies adopted by GNB to counteract the activity of antimicrobial molecules. The broad spectrum of activity against different GNB species, the potent antibacterial activity, the pharmacokinetics properties, safety, and tolerability render cefiderocol a fundamental drug for the treatment of infections due MDR strains. Although this novel antimicrobial molecule has revolutionized the therapeutic antimicrobial armamentarium against MDR-GNB, the recent emergence of cefiderocol resistant strains have redefined its role in clinical practice and requested novel strategies to preserve its antibacterial activity. In this review, we discuss the mechanism of action of Cefiderocol, emerging resistance mechanisms, pharmacokinetic/pharmacodynamic (PK/PD) properties, efficacy data against the main Gram-negative bacteria, and future prospectives.

Salt stress is one of the major abiotic stresses that lead to crop yield reduction worldwide. Melatonin (MT), an endogenous hormone synthesized in plants, plays an important role in responding to abiotic stimuli such as drought, salinity, heat, cold, etc. However, the molecular mechanisms of MT-mediated abiotic stresses remain to be better understood. In order to explore the key genes and pathways of melatonin in alleviating salt stress, physiological and biochemical indicators as well as transcriptomics profile were conducted in alfalfa seedlings. The results showed that the germination rate, bud length and fresh weight of alfalfa seedlings added with melatonin were higher than those treated with salt alone. In addition, Malondialdehyde (MDA) and Superoxide anion (O2-) contents also displayed a decreasing trend. The activity and content of Superoxide dismutase (SOD)、peroxidase (POD) and Glutathione (GSH) increased to varying degrees. In order to further reveal the molecular mechanism of MT-mediated salt tolerance of alfalfa, transcriptome analysis was performed on alfalfa seedlings. 2,181 differentially expressed genes (DEGs) were obtained in the salt-treated group, including 780 upregulated genes and 1,401 down-regulated genes, while 4,422 DEGs were obtained in the MT group, among which 1,438 were upregulated and 2,984 were downregulated. By using GO functional annotation and KEGG pathway enrichment, we found that DEGs were mainly enriched in the biosynthesis of flavonoids, isoflavones, plant hormones, Glutathione (GSH), soluble sugars and other substances, as well as in the ABC transporter and MAPK signaling pathways. Among them, the DEGs in the MT group was more enriched in these pathways, suggesting that MT can combat salt stress by regulating the expression of genes related to phytohormone and antioxidant capacity, which has important reference value for the breeding of salt-tolerant alfalfa and other crops.

Early weaning management followed by energy supplementation can lead to metabolic alterations in the calf that exert long-term effects on the animal’s health and performance. It is believed that the main molecular basis underlying these metabolic adaptations are epigenetic mechanisms that regulate, activate, or silence genes at different stages of development and/or in response to different environmental stimuli. However, little is known about postnatal metabolic programming in Bos indicus. Therefore, this study aimed to compare the DNA methylation profile of Nellore animals submitted to conventional and early weaning and to correlate the findings with genes differentially expressed in Longissimus thoracis skeletal muscle of Bos indicus cattle. A total of 481 differentially methylated regions were identified, with 52% (250) being hypermethylated and 48% (231) hypomethylated. Functional enrichment analysis of 53 differentially methylated and differentially expressed genes was performed. The main enriched terms and pathways were associated with 3’-5’-cyclic adenosine monophosphate (cAMP) signaling which present the upregulated adenylate cyclase 3 (ADCY3) gene and significatively hypomethylated in promoter region. Alterations in cAMP signaling are involved in numerous processes, many of them related to lipid metabolism. The relative differential expression of key genes of this pathway demonstrates the relationship between cAMP signaling and de novo lipogenesis. These findings suggest an important role of postnatal metabolic programming through DNA methylation mechanisms in determining fat deposition in beef.

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer, and is the third leading cause of cancer-related deaths each year. It involves a multi-step progression and is strongly associated with chronic inflammation induced by the intake of environmental toxins and/or viral infections (i.e., hepatitis B and C viruses). Although several genetic dysregulations are considered to be involved in disease progression, the detailed regulatory mechanisms are not well defined. Homeobox (Hox) genes that encode transcription factors with homeodomains control cell growth, differentiation, and morphogenesis in embryonic development. Recently, more aberrant expressions of Hox genes were found in a wide variety of human cancer, including HCC. In this review, we summarize the currently available evidence related to the role of Hox genes in the development of HCC. The objective is to determine the roles of this conserved transcription factor family and its potential use as a therapeutic target in future investigations.

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, increasing evidence indicates that Pdcd4 enhances the chemosensitivity of several chemotherapeutic drugs. To date, several translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may enhance chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

Inflammation and insulin resistance are recognized as central features in the pathology of psoriasis, profoundly affecting the lives of those affected by this condition. The relationship between lifestyle choices and psoriasis is well-documented, highlighting the potential benefits of dietary modifications and physical activity in managing the condition during exacerbations. Furthermore, growing evidence emphasizes the significant impact of nutritional interventions on various skin disorders, particularly those characterized by inflammation and insulin dysregulation. Notably, the role of dietary fats is of particular interest, with their influence on inflammation and insulin resistance in psoriasis garnering increasing attention. Moreover, the association between excessive adiposity and heightened psoriatic severity underscores the importance of weight management strategies in disease management. This review explores the intricate relationship between specific dietary fats and inflammation in psoriasis, offering a comprehensive analysis of their implications for disease progression and management.

Escherichia coli is the main pathogen responsible for extraintestinal infections. A total of 196 clinical E. coli consecutively isolated during 2016 in Spain (100 from Lucus Augusti hospital in Lugo) and France (96 from Beaujon hospital in Clichy) were characterized. Phylogroups, clonotypes, sequence types (STs), O:H serotypes, virulence factor (VF)-encoding genes and antibiotic resistance were determined. Approximately 10% of the infections were caused by ST131 isolates in both hospitals and approximately 60% of these infections were caused by isolates belonging to only 10 STs (ST10, ST12, ST58, ST69, ST73, ST88, ST95, ST127, ST131, ST141). ST88 isolates were frequent especially in Spain while ST141 isolates significantly predominated in France. The 23 ST131 isolates displayed four clonotypes: CH40-30, CH40-41, CH40-22 and CH40-298. Only 13 (6.6%) isolates were carriers of ESBL enzymes. However, 37.2% of the isolates were multidrug-resistant (MDR). Approximately 40% of the MDR isolates belonged to only four of the dominant clones (B2-CH40-30-ST131, B2-CH40-41-ST131, C-CH4-39-ST88 and D-CH35-27-ST69). Among the remaining MDR isolates two isolates belonged to B2-CH14-64-ST1193 i.e the new global emergent MDR clone. To our knowledge, it is the first identification of this emergent clone in Spain. Moreover, a hybrid ExPEC/enteroaggregative isolate belonging to A-CH11-54-ST10 clone was identified.

Shape memory alloys (SMA) are becoming a more important factor in actuation technology. Due to their unique features, they bring the potential to safe weight, installation space and reduce energy consumption. The system integration of the generally small diameter NiTi wires is an important cornerstone for the emerging technology. Crimping, a common method for the mechanical and electrical connection of SMA wires, has several drawbacks when it comes to miniaturization and high force outputs. For high force applications for example, multiple SMA wires in parallel are needed to keep actuation frequencies high, while scaling up the actuation force. To meet these challenges, the proposed study deals with the development of a resistance welding process for manufacturing NiTi wire bundles. The wires are welded to sheet metal substrate, resulting in promising functional properties and high joint strengths. The welding process benefits from low cost, easy to control parameters and good automation potential. A method for evaluating the resistance welding process parameters is presented. With these parameters in place, a manufacturing process for bundled wire actuators is discussed and implemented. The welded joints are examined by peel tests, microscopy, and fatigue experiments. The performance of the manufactured bundle actuators is demonstrated by comparison to a single wire with the same accumulated cross-sectional area.

Excess nitrogen in agricultural drainage poses a serious threat to the water quality safety of the Yellow River basin. Utilizing aquatic plants to modify the rhizosphere microbial community structure and facilitate nitrogen transformation is a crucial strategy for mitigating regional water eutrophication. Our results revealed that the denitrification rate (DR), dissimilatory nitrate reduction to ammonium rate (DNRAR) and nitrogen fixation rate (NFR) of rhizosphere sediments exhibited a significant increase in artificially cultivated ditch. Compared with those in natural ditches, the richness of the bacterial community and the relative abundances of Bacteroidota, Verrucomicrobiota, Firmicutes, Anaeromyxobacter and Geobacter, which are involved mainly in the nitrogen cycle, in the rhizosphere sediments of artificially cultivated ditch were significantly greater due to improvements in environmental conditions. In artificially cultivated ditch, the dominant functional genes affecting DRNARs in the rhizosphere sediments of P. australis were nrfC and nrfA, while DRs were driven mainly by norB and napA, which were influenced by the nitrogen and carbon levels; and the dominant functional genes affecting NFRs in the rhizosphere sediments of T. orientalis were nifD, nifK and nifH. Our results provide a scientific basis for the use of aquatic plants for mitigating excess nitrogen levels in agricultural drainage.

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.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

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.

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have an elevated resistance to exogenous antimicrobial peptides (AMPs) – both, with regard to peptide bulk concentration in the medium, and the numbers of peptide molecules per cell. By monitoring integration of the AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy-coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.

Developing new antibiotics poses a significant challenge in the fight against antimicrobial resistance (AMR), a critical global health threat responsible for approximately 5 million deaths annually. Finding new classes of antibiotics that are safe, have acceptable pharmacokinetic properties, and are appropriately active against pathogens is a lengthy and expensive process. Therefore, high-throughput platforms are needed to screen large libraries of synthetic and natural compounds. In this review, we present bacterial cytological profiling (BCP) as a rapid, scalable, and cost-effective method for identifying the mechanisms of action of antibiotics, offering a promising tool for combating AMR and drug discovery. We present the application of BCP for different bacterial organisms and different classes of antibiotics and discuss BCP's advantages, limitations, and potential improvements. Furthermore, we highlight the studies that have utilized BCP to investigate pathogens listed in the Bacterial Priority Pathogens List 2024 and we identify the pathogens whose cytological profiles are missing. Lastly, we explore the most recent artificial intelligence and deep learning techniques that could enhance the analysis of data generated by BCP, potentially advancing our understanding of antibiotic resistance mechanisms and the discovery of novel druggable pathways.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

Selection is a fundamental part of the plant breeding process, enabling the identification and development of varieties with desirable traits. Thanks to advances in genetics and biotechnology, the selection process has become more precise and efficient, resulting in faster breeding progress and better adaptation of crops to environmental challenges. Genetic parameters related to gene additivity and epistasis play a key role and can influence decisions on the suitability of breeding material. In this study, 188 rapeseed doubled haploid lines were assessed in field conditions for resistance to Leptosphaeria spp. Through next-generation sequencing, a total of 133,764 molecular markers (96,121 SilicoDArT and 37,643 SNP) were obtained. The similarity of the DH lines at the phenotypic and genetic levels was calculated. The results indicate that the similarity at the phenotypic level was markedly different than the similarity at the genetic level. Genetic parameters related to additive gene action effects and epistasis (double and triple) were calculated using two methods: based on phenotypic observations only and using molecular marker observations. All evaluated genetic parameters (additive, additive-additive and additive-additive-additive) were statistically significant for both estimation methods. The parameters associated with the interaction (double and triple) had opposite signs depending on the estimation method.

Aim: We estimated the correlation between serum bilirubin concentrations and insulin resistance in advanced maternal age without diabetes mellitus. Method: The cross-sectional study involved consecutive 50 women of advanced maternal age without diabetes mellitus, and insulin resistance (IR) was diagnosed according to the homeostatic model assessment insulin resistant (HOMA-IR) formula and the cut-off point was set to more than 2.5. Serum bilirubin and HOMA-IR were compared between the IR (+) and IR (-) groups. Results: We found that serum bilirubin levels in the IR subjects were significantly decreased compared to those without IR (p = 0.0252). Serum bilirubin concentrations were negatively correlated with the weight and the fasting insulin concentrations in all subjects (r=−0.282, p=0.047, r=-0.424, p=0.002). Additionally, serum bilirubin had a negatively correlation with HOMA-IR (r = -0.410, p = 0.003) in all subjects. The multiple linear regression analysis found that serum total bilirubin levels were independently correlated with HOMA-IR (beta = -0.392, p= 0.015) in these subjects. Conclusions: The study demonstrated that serum bilirubin concentrations had negatively correlation with insulin resistance in advanced pregnant women without diabetes mellitus, and decreased serum bilirubin may forebode increased gestational diabetes mellitus risk in our study population.

The epidemic of obesity has increased worldwide and is associated with comorbidities as diabetes as cardiovascular disease. Strategies that modulate body weight and improves glycemic metabolism has increased, and the bariatric surgeries as Sleeve Gastrectomy (SG) has been highlighted in obesity treatment. However, the mechanism by which SG reduces body weight and improves glycemic control are unknow. C57BL mice were submitted to a 10 weeks high fat-diet protocol and submitted to SG. Food intake, fed/fasted glycemia and hypothalamic anorexigenic and orexigenic gene expression were evaluated. SG reduces body weight, fasting glycemia, insulinemia and leptinemia in obese mice. Moreover, SG reduces food and total calorie intake with no alterations in the expression of anorexigenic and orexigenic gene expression. These data indicates that SG improves obesity associated alterations, at least in part, by reduction on food intake. This effect is not associated with the classic food intake pathway in hypothalamus, indicating the involvement of supplementary pathways in this process.

Kynurenic acid (KYNA), a tryptophan metabolite, is believed to exert neuromodulatory and neuroprotective effects in the brain. The study aimed to examine the KYNA’s capacity to modify gene expression and the activity of cellular antioxidant enzymes in specific structures of the sheep brain. Anestrous sheep were infused intracerebroventricularly with two KYNA doses: lower (4×5 μg/60 μL/30 min, KYNA20) and higher (4×25 μg/60 μL/30 min, KYNA100) at 30min intervals. The abundance of superoxide dismutase (SOD2), catalase (CAT) and glutathione peroxidase (GPx1) mRNA, as well as enzyme activities (µM/µg of protein), were determined in the hypothalamic medial-basal (MBH) and preoptic (POA) areas, and in the hippocampal CA1 field. Both doses of KYNA caused a decrease (P&lt;0.01) in the expression of SOD2 and CAT mRNA in all structures examined compared to the control group (except for CAT in the POA at the KYNA100 dose). Furthermore, lower levels of SOD2 mRNA (P&lt;0.05) and CAT mRNA (P&lt;0.01) were found in the MBH and POA and in the POA and CA, respectively, in sheep administered with the KYNA20 dose. Different stimulatory effects on GPx1 mRNA expression were observed for both doses (P&lt;0.05-P&lt;0.01). KYNA exerted stimulatory, but dose-dependent effects on SOD2, CAT and GPx1 activities (P&lt;0.05-P&lt;0.01) in all brain tissues examined. The results indicate that KYNA may influence the level of oxidative stress in individual brain structures in sheep by modulating the expression of genes and activity of at least SOD2, CAT and GPx1. The present findings also expand the general knowledge about the potential neuroprotective properties of KYNA in the central nervous system.

The rise of antibiotic-resistant bacteria in clinical settings has become a significant global concern. Among these bacteria, Acinetobacter baumannii stands out due to its remarkable ability to acquire resistance genes and persist in hospital environments, leading to some of the most challenging infections. Horizontal gene transfer (HGT) plays a crucial role in the evolution of this pathogen. The A. baumannii AMA205 strain, belonging to sequence type ST79, was isolated from a COVID-19 patient in Argentina in 2021. This strain’s antimicrobial resistance profile is notable as it harbors multiple resistance genes, some of which had not been previously described in this species. The AmpC family β-lactamase blaCMY-6, commonly found in Enterobacterales, had never been detected in A. baumannii before. Furthermore, this is the first ST79 strain known to carry the carbapenemase blaNDM-1 gene. Other acquired resistance genes include the carbapenemase blaOXA-23, further complicating treatment. Susceptibility testing revealed high resistance to most antibiotic families, including cefiderocol, with significant contributions from blaCMY-6 and blaNDM-1 genes to the cephalosporin and carbapenem resistance profiles. The A. baumannii AMA205 genome also contains genetic traits coding for 111 potential virulence factors, such as the iron-uptake system and biofilm-associated proteins. This study underscores A. baumannii's ability to acquire multiple resistance genes and highlights the need for alternative therapies and effective antimicrobial stewardship to control the spread of these highly resistant strains.

Most cervical cancer cases are a result of persistent high-risk Human papillomavirus (HPV) infections. Cervical cancer is prevalent in LMICs especially in SSA where it is second most prevalent cancer. In South Africa, it is the second most common cancer affecting women aged between 15 and 44 years. The host immune response has been shown as an important factor in controlling the progression or regression of high-risk HPV infection of the cervix to cervical cancer. The risk of cervical cancer is known to be influenced by the host's genetic diversity, particularly by immune response-regulating genes such as the Human Leukocyte Antigen (HLA) class I and II genes. HLA class I genes present viral peptides to CD8+ T cells which are restricted and pre-programmed for cytotoxic functions. There is very little known about the HLA genes of South African women and how these influence outcome of HPV infections. This review aims to understand the role and influence of HLA class I genes in HPV clearance, persistence, and CD8+ T cell mediated immunity in African women by examining existing literature in this area. Understanding this role can influence and inform therapeutic vaccine design that is population specific.

Wear-resistant steel/carbon steel composite plate not only has the double performance advantage of high strength and wear-resistance, but also can reduce energy consumption and production cost. Based on 50% reduction rate, the wear resistance of BTW1/Q345 composite was studied at different annealing temperatures, and the dry friction and wear tests of BTW1/Q345 composite at different annealing temperatures were carried out by using RETC MFT-5000. The macro-micro morphology and wear mechanism of wear marks at different annealing temperatures were analyzed by using white light interference three-dimensional surface profiler, Scanning electron microscope scanning electron microscope (SEM) and backscatter electron diffraction (EBSD) . The results show that with the increase of annealing temperature, the grain size near the scratch of BTW1 in the wear-resistant layer of the composite plate is refined, and the wear-resistant property is higher than that of the original sample.When the annealing temperature is 860℃,the wear resistance is the best.

Soybean is the primary oilseed crop in the United States, with significant industrial value. Understanding the molecular mechanisms of heat stress tolerance in soybean is critical for developing stress-resistant cultivars. Current knowledge about the role of fatty acid desaturases (FADs) in modulating membrane fluidity under abiotic stress prompted this investigation into the impact of mutations in the FAD genes on seed germination from heat-stressed plants. In soybean, exposure to heat stress during anthesis is known to significantly reduce seed germination. In silico expression analysis indicated high levels of expression of the soybean FAD2 and FAD3 genes in leaves. Therefore, a detailed expression analysis of these genes was conducted using qRT-PCR from leaf tissue. Generally, downregulation of these genes was observed in the mutants; however, two genes, FAD3A and FAD2-3, showed a more than 2-fold increase in expression in six out of ten mutants under heat stress. This upregulation was particularly pronounced (7-fold) in mutant S17CR-170. Correlation analysis revealed a positive correlation (0.5) between the expression level of FAD3A, FAD3B, FAD3C, and FAD2-3 and the decline in germination from heat-stressed plants. This suggests these FAD genes may act as negative regulators of germination under heat stress conditions.