Regeneration of lost tail is of great importance to lizards. Anolis carolinensis, a green lizard, is capable of regenerating its tail efficiently after autotomy. Hence, it is considered as a model organism in regeneration study. A. carolinensis shed its tail in order to distract the predator’s attention and thus makes a way to escape. Restoring of the amputated tail takes several days and the mechanism is currently clearly understood. Although save its life, tail regeneration is associated with the impairment of several vital functions in Anoles. In addition, various differences have been observed between original and regenerated tail in terms of mechanism and structure. To date, very little work has been conducted on tail autotomy and regeneration at molecular and genetic level. The genes responsible for regeneration in anoles are identified recently. These genes are evolutionarily conserved through all tetrapod vertebrates. They are, however, in a state of ‘switched-off’ in other vertebrates including humans. Consequently, a throughout study of these so called ‘switched-off’ genes may provide a way of restoring lost organs in human, and thus could revolutionize the modern medical science.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

Oligopeptide transporters (OPTs) are a group of membrane localized proteins that have a broad range of substrate transport capabilities and contribute to numerous biological processes. However, limited information has been reported on OPTs in higher plants. In this study, a comprehensive analysis of the OPT gene family in Medicago truncatula was performed. A total of 26 OPT genes (MtOPT01-MtOPT26) have been identified in the Medicago truncatula genome. Phylogenetic analyses indicated that MtOPTs consisted of two distinct subgroups, 12 MtOPTs belonged to the peptide transport subgroup (PT-OPT) based on their predicted amino acid sequences containing the two highly conserved motifs (NPG and KIPPR) and 14 MtOPTs belonged to yellow stripe subgroup (YS-OPT). The MtOPTs distributed on each of 8 chromosomes in Medicago truncatula. Sequence analysis verified that MtOPTs significant similar to those in other plants. The copy number of MtOPTs was low and the multiply of MtOPTs was simple relatively. Gene structure analysis showed that most of the MtOPTs have various numbers of introns. The multiple of MtOPTs might play different biological roles which were supported by the fact that MtOPTs have a distinct tissue-specific expression pattern. The data obtained in this study will help to better understand the complexity of the MtOPTs gene family and provide new evidence for the function and evolution of the OPT gene family in higher plants.

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.

Lumpy skin disease (LSD), caused by a virus within the Poxviridae family and Capripoxvirus genus, induces nodular skin lesions in cattle, spreading through direct contact and insect vectors, significantly affecting global cattle farming. Despite available vaccines, their effectiveness is limited by poor bioavailability and adverse effects. Our study aimed to identify potential inhibitors targeting LSD-associated DNA polymerase protein, selecting LSDV039 for further investigation through comprehensive analysis and computational methods. Virtual screening revealed rhein and taxifolin as potent binders among 380 phytocompounds, with respective affinities of -8.965 and -7.195 kcal/mol. Canagliflozin and tepotinib exhibited strong affinities (-9.858 and -8.856 kcal/mol) among 718 FDA-approved antiviral drugs. Molecular dynamics simulations of canagliflozin, tepotinib, rhein, and taxifolin highlighted taxifolin's superior stability and binding energy. Rhein displayed compactness in RMSD and RMSF but fluctuations in Rg and SASA, while canagliflozin demonstrated stability compared to tepotinib. The study highlights the promising potential of repurposed drugs and phytocompounds as LSD therapeutics. However, extensive validation through in-vitro, in-vivo, and clinical trials is crucial for their practical application.

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

Many types of banana (Musa spp.)—one of the most economically important horticultural crops—exist, and their ploidy (diploid, triploid, and tetraploid, usually) and genome types (containing A or/and B genome in most cases) differ. At present, observation and genome type detection are commonly used to identify banana germplasm resources. However, the former is tedious, while the latter cannot distinguish categories below genome types. It is therefore urgent that a simple and effective method for identifying banana germplasm resources is established. We sequenced and analyzed the ribosomal DNA internal transcribed spacer (ITS) sequences of 62 banana germplasm and found that the sequencing peaks, especially the 20 bp region near the 420 bp position (referred to as the “420 bp region”), exhibited relatively recognizable and repeatable polymorphism characteristics. Using the “420 bp region” as a marker, we were able to quickly distinguish bananas belonging to different genome type groups (comprising the AA, AB, AAA, ABB, AAB, ABBB, AAAB, and AAAA groups) or different subgroups in the same genome type group (for example, the Cavendish, Gros Michel, Red, Lakatan, and Ibota Bota subgroups in the AAA group; and the Pisang Raja, Plantain, Pome and Silk subgroups in the AAB group). Moreover, it appeared that Sanger sequencing of ITS could be used for identifying banana hybrid offspring. These results demonstrated that the banana ITS region contains rich genetic information that is useful for genotyping. In general, ITS sequencing simplifies the classification of banana germplasm resources and has potential application in several areas of Musa improvement.

Climate change, growing world population and increasing food demand require higher yields and adaptability of crops, including spring bread wheat. Modern plant breeding based on achievements of genetics has a significant impact on plant resistance to diseases, climate variability and other factors. Genome wide association studies (GWAS) is one of genetics tools for mining of genome loci associated with economically important traits. In the current study, we applied GWAS to reveal QTL for spike productivity and grain quality using a panel of spring varieties of Triticum aestivum L. bred in different decades of the last century in Russia and Germany. The study has enabled to find new genetic markers associated with grain yield and quality. Studying genetic basis of grain yield and quality by comparison of wheat varieties from different breeding periods, including landraces preserved as the source of valuable genetic diversity for breeding and genetic studies, makes it possible not only to understand selection processes in the past, but also to develop strategies for future breeding work.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI) resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects.

Drosophila melanogaster serves as a important research model both for genetic investigations and for the study of metal toxicity, facilitating the elucidation of physiological mechanisms comparable to those of human organisms. In our research, we evaluated the toxicity effect resulting from exposure to various concentrations of lead and copper on the prolificity rates throughout the life cycle (egg-adult) of four genotypes of Drosophila melanogaster: wild-type (control), white, brown, and white-vestigial. During our study, the prolificity rates were examined across three repetitions under the impact of exposure to concentrations of 0.50, 1.00, 2.00, and 4.00 mM of copper (CuSO₄) and lead (Pb(C₂H₃O₂₎₂). Prolificity rates throughout the life cycle exhibited variations as a direct consequence of genetic factors, the concentration of exposure, and the specific type of metal, either copper or lead. The mutant white-vestigial genotype revealed an IC₅₀ concentration for prolificity inhibition at lower doses of 2.00 mM for copper and 4.00 mM for lead, in contrast to the control genotype (wild-type), which exhibited an inhibition concentration rate >IC₅₀ of 4.00 mM only in the case of copper. Our results concluded that the (i) dose influences the prolificity rate in a directly proportional manner, (ii) comparative analyses between copper and lead revealed that copper displayed toxicity across all genotypes within the concentration range of 0.50 mM to 2.00 mM. In contrast, lead exhibited toxicity within the concentration range of 1.00 mM to 4.00 mM, highlighting a (iii) more acute toxicity characteristic in the case of copper. Thus, the results of this research reflect the importance of using Drosophila melanogaster as a genetic model in the comparative study of the interaction between genetic factors and the toxicity of metals, offering significant insights into monitoring their impact and defining the maximum permissible doses on organisms.

Fourteen Russian potato cultivars (cvs.) grown for three years in field plots of VIR (Northwestern region of the Russian Federation) were evaluated for productivity and a number of biochemical parameters of tubers. The 12 parameters that have been evaluated in tubers annually one month after harvesting and after cold storage (at 2 - 4°C) include the content of dry matter, starch, protein, ascorbic acid, carotenoids and β-carotene, anthocyanins, total sugars and monosaccharides (reducing sugars), phenolic compounds, as well as total acidity, and antioxidant activity. The cultivars differed significantly in productivity and biochemical composition of tubers. Dry matter content ranged from 16.40% in cv. ʻKumachʼ to 27.28% in ʻNayadaʼ, starch content ranged from 8.96 % in cvs. ʻFioletovyjʼ, ʻKumachʼ to 20.08% in ‘Sokur’, the total sugar content reached 2.46% in cv. ʻSiverskij’ whereas ‘Sokur’ has the smallest content of reducing sugars in post-harvest tubers. Protein content ranged from 1.02% to 2.77% with the highest accumulation in cv. ʻSokurʼ. Content of ascorbic acid (vitamin C) ranged from 6.3 mg/100 g FW in ʻKrasa Meŝeryʼ to 26.6 mg/100 g FW in cv. ʻKrasavchikʼ. Carotenoids content ranged from 0.157 mg/100 g FW in cv. ‘Nayada’ to 0.645 mg/100 g FW in cv. ʻGrandʼ. Content of anthocyanins in potato ranged from 1.04 mg/100g FW (not colored tubers of cv. ʻKrasa Meŝeryʼ) to 283.04 mg/100g FW (colored tubers of cv. ʻFioletovyiʼ). The nutritional value of tubers (content of dry matter, sugars, starch and protein) was determined to a greater extent (38-49%) by varietal characteristics, rather than by meteorological conditions in vegetation period. The content of vitamin C, carotenoids, protein and anthocyanins varied depending on the year. The highest content of dry matter, starch and carotenoids was noted in tubers harvested in 2019, marked by low temperatures and precipitation deficit in growing season. The conditions of 2020 with low temperatures and excess precipitation were the most favorable for anthocyanin’s accumulation in potato tubers while not for other biochemical parameters. Of the cultivars, ʻSokurʼ had the highest content of dry matter, protein and starch. Cv. ʻFioletovyiʼ had small starch content and high level of anthocyanins. Cv. ʻPlamyaʼ can be recommended for potato products manufacturing due to dry matter content above 20% and reducing sugars content 0.24%..

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

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

Glioblastoma (GBM) is the most common malignant brain tumor in adults. Despite advancements in treatment, the prognosis for patients with GBM remains poor due to its aggressive nature and resistance to therapy. CRISPR-based genetic screening has emerged as a powerful tool for identifying genes crucial for tumor progression and treatment resistance, offering promising targets for tumor therapy. In this review, we provide an overview of the recent advancements in CRISPR-based genetic screening approaches and their applications in GBM. We highlight how these approaches have been used to uncover genetic determinants of GBM progression and susceptibility to various therapies. Furthermore, we discuss ongoing challenges and future directions of CRISPR-based screening methods in advancing GBM research.

Fusarium spp. are commonly associated with the root rot complex of soybean (Glycine max). Previous surveys identified six common Fusarium species from Manitoba, including F. oxysporum, F. redolens, F. graminearum, F. solani, F. avenaceum and F. acuminatum. This study aimed to determine their pathogenicity, assess host resistance and evaluate the genetic diversity of Fusarium spp. isolated from Canada. Pathogenicity was tested on two cultivars, ‘Akras’ (moderate resistance) and ‘B150Y1’ (susceptible), under greenhouse conditions. The virulence of the fungal isolates varied, with root rot severities ranging from 1.5 to 3.3 on a 0-4 scale. The six species were used to screen a panel of 20 Canadian soybean cultivars for resistance in a greenhouse. Cluster and principal component analyses were conducted based on the same traits as for the pathogenicity study. Two of the cultivars, ‘P15T46R2’ and ‘B150Y1’, were consistently found to be tolerant to F. oxysporum, F. redolens, F. graminearum and F. solani. To investigate the incidence and prevalence of Fusarium spp. in Canada, fungi were isolated from 106 soybean fields surveyed across Manitoba, Saskatchewan, Ontario and Quebec. Two-hundred twenty-one Fusarium isolates were identified, with phylogenetic analyses indicating diversity of the isolates in the major soybean production regions of Canada.

Abiotic stresses extensively reduce agricultural crop production globally. Traditional breeding approaches have been widely used to mitigate the risks of abiotic stresses. The discovery of gene editing technology for modifying stress-responsive genes and associated molecular networks has paved the foundation for sustainable crop management against environmental stress. Integrated approaches based on functional genomics and transcriptomics are now expanding the opportunities to elucidate the molecular mechanisms underlying abiotic stress responses. This review summarizes some of the features and weblinks of plant genome databases related to abiotic stress genes utilized for crop improvement. Clustered, regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas) based gene-editing tool has revolutionized stress tolerance research due to its simplicity, versatility, adaptability, flexibility, and broader applications. However, off-target and low cleavage efficiency hinder the successful application of CRISPR/Cas systems. Computational tools have been developed for designing highly competent gRNA with better cleavage efficiency. This powerful genome editing tool offers tremendous crop improvement opportunities, overcoming conventional breeding techniques' shortcomings. Furthermore, we also discuss the mechanistic insights of the CRISPR/Cas9-based genome editing technology. This review summarizes the current advances in understanding plant species' abiotic stress response mechanism and applying the CRISPR/Cas system genome editing technology to develop crop resilience against drought, salinity, temperature, heavy metals, and herbicides.

This study aimed to characterize the genetic subtypes of HCV-GT4 and identify the presence of natural occurring resistance-associated substitutions (RASs) in Saudi Arabia patients. A total of 17 GT4 patients was analyzed. Sequence analysis of NS3, NS5A and NS5B regions was performed by direct sequencing. In addition, phylogenetic analysis was used to determine genetic subtypes, RAS and polymorphisms. Nine patients were infected by a GT4a, one with GT4o, 3 with GT4d. The remaining four patients were infected with a recombinant virus (GT4a+GT4o in three patients, GT4c+GT4d in a patient). Natural RASs were found in six patients (35%), including three infected by GT4a, two by GT4a+GT4o and one patient infected by GT4c+GT4d. In particular, NS3-RAS V170I was demonstrated in three patients, while NS5A-RASs (L28M, L30R, L28M+M31L) were detected in the remaining three patients. All patients were treated with sofosbuvir plus daclatasvir; three patients were lost to follow-up whereas 14 patients completed the treatment. A sustained virological response (SVR) was obtained in all but one patient carrying NS3-RAS V170I who later relapsed. GT4a is the most common subtype in this small cohort of Saudi Arabia patients infected with hepatitis C infection. Natural RASs were observed in about a third of patients, but only one of them showed a treatment failure.

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.

Enterococci are widely acknowledged as prominent pathogens in hospitals, with the potential to transfer resistance genes, virulence factors, or other characteristics that increase their ability to survive in humans. Healthy cattle, sheep, and goats can be reservoirs for gastrointestinal pathogenic fecal enterococci, some of which could be multidrug-resistant to antimicrobials. The objective of this study was to determine the prevalence and diversity of Enterococcus species in healthy sheep, goat, and cattle carcasses, as well as to analyze the antimicrobial resistance phenotype/genotype and the virulence gene content. During 2019–2020, carcass surface samples of 150 ruminants were collected in a slaughterhouse. A total of 90 enterococci, comprising 5 species, were obtained. The overall prevalence of enterococci was found to be 60%, out of which 37.7% were identified as E. hirae, 33.3% as E. casseliflavus, 15.5% as E. faecium, 12.2% as E. faecalis, and 1.1% as E. gallinarum. Virulence-associated genes of efaA (12.2%) were commonly observed in the Enterococcus isolates, followed by gelE (3.3%), asaI (3.3%), and ace (2.2%). Characteristic resistance genes were identified by PCR with an incidence of 6.6%, 2.2%, 1.1%, 1.1%, 1.1%, and 1.1% for the tetM, ermB, ermA, aac(6’)Ie-aph(2")-la VanC1, and VanC2 genes, respectively. The high resistance to quinupristin-dalfopristin (28.8%), tetracycline (21.1%), ampisilin (20%), and rifampin (15.5%) was distributed among two, four, four, and five of the five species, respectively. The resistance of Enterococcus isolates to 11 antibiotic groups was determined and multidrug-resistant (MDR) strains occupied 18.8% of the Enterococcus isolates. Efflux pump genes causing multidrug resistance were detected in Enterococcus isolates (34.4%). The study's results showed that there were enterococci in the slaughterhouse that were multidrug resistant (MDR) and had a number of genes linked to virulence that could be harmful to human health.

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.

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

Verticillium wilt (VW) is an important and widespread disease of cotton and once established is long lived and difficult to manage. In Australia, the non-defoliating pathotype of Verticillium dahliae is the most common, and extremely virulent. Breeding cotton varieties with increased VW resistance is the most economical and effective method of controlling this disease and is greatly aided by understanding the genetics of resistance. In this study, VW resistance was investigated in 240 F7 recombinant inbred lines (RIL) derived from a cross between MCU-5 that has good resistance and Siokra 1-4 which is susceptible. Using a controlled environment bioassay, we found that resistance based on plant survival or shoot biomass was complex but with major contributions from chromosomes D03 and D09, with genomic prediction analysis estimating a prediction accuracy of 0.73 based on survival scores compared to 0.36 for shoot biomass. Transcriptome analysis of MCU-5 and Siokra 1-4 roots uninfected or infected with V. dahliae revealed that the two cultivars displayed very different root transcriptomes and responded differently to V. dahliae infection. Ninety-nine differentially expressed genes were located in the two mapped resistance regions and so are potential candidates for further identifying the genes responsible for VW resistance.

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

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.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

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

The conventional well placement was done manually by using a numerical reservoir simulator, and it required a lengthy trial-and-error process. It required great experience and expertise to manipulate the variables and uncertainties that lie on the reservoir to determine the best placement of the well. In addition, the traditional gradient-based methods such as Line-search and Trust-region were not viable in terms of maximum results obtained. Gradient-based methods were too dependent on the surface gradient of the solution and may only converge to local optima instead of global optima. Complex reservoirs have rough surfaces with high uncertainties, which hinders the traditional gradient-based method from converging to global optima. Thus, genetic algorithms were utilized to automate the manual trial-and-error process and to overcome the limitations of the traditional gradient-based method. The objectives of this study were to analyse the effect of different initial well placement distributions, the number of random solution sizes, and the crossover rate on cumulative oil production. A synthetic reservoir model built using CMG Builder was used as the testing platform for the optimization problems. Well-placement parameterization and optimization set-up were carried out using the CMG CMOST optimization tool. The integration of CMG IMEX and CMOST optimized cumulative oil production based on the objectives of the study. The results obtained showed that the higher number of random solutions used resulted in higher cumulative oil production, with more generations needed to reach the optimum solution. It can be concluded that the larger number of random solutions used increased the probability of reaching the optimum solution, but will take more generations.

The African continent has the highest prevalence of hypertension globally, with South Africa reporting the highest prevalence in Southern Africa. While the influence of genetic variability in the pathogenesis of hypertension is well described internationally, limited reports are available for African populations. This study aimed to assess the association of genetic variants and essential hypertension in a cohort of two ethnic South African population groups. Two hundred and seventy-seven hypertensive and one hundred and seventy-six normotensive individuals were genotyped for 79 variants. Genotyping was performed using the Illumina GoldenGate Assay and allele-specific polymerase chain reaction. The association of variants was assessed using the Fisher Exact test under the additive and allelic genetic models, while multivariate logistic regression was used to predict the development of hypertension. Five variants (CYP11B2 rs179998, AGT rs5051 and rs699, AGTR1 rs5186 and ACE rs4646994) were significantly associated with essential hypertension in the cohort under study. Furthermore, AGTR1 rs5186 and AGT rs699 were identified as risk factors for the development of hypertension in both ethnic groups. In two ethnic South African populations an association was observed between Renin-Angiotensin-Aldosterone System (RAAS) related genes and the development of hypertension.

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.

Dysferlinopathies comprise a spectrum of muscular dystrophies characterized by progressive muscle weakness and degeneration due to mutations in the DYSF gene, which encodes the dysferlin protein critical for muscle membrane repair. This review delves into the clinical spectra of dysferlinopathies, their molecular mechanisms, and the spectrum of emerging therapeutic strategies. We explore the phenotypic heterogeneity of dysferlinopathies, highlight the incomplete understanding of genotype-phenotype correlations, and discuss the implications of various DYSF mutations. Furthermore, we examine the utility of animal models in elucidating disease mechanisms and the potential of symptomatic, pharmacological, molecular, and genetic therapies in mitigating the disease's progression. We also consider the roles of diet and metabolism in managing dysferlinopathies, as well as the impact of clinical trials on treatment paradigms. By culminating the complexities inherent in dysferlinopathies, this article emphasizes the need for multidisciplinary approaches, precision medicine, and extensive collaboration in research and clinical trial design to advance our understanding and treatment of these challenging disorders.

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.

Several herbivores feed on maize in field and storage setups making the development of multiple-insect resistance a critical breeding target. In this study, an association mapping panel of 341 tropical maize lines was evaluated in three field environments for resistance to FAW (fall armyworm) whilst bulked grains were subjected to MW (maize weevil) bioassay, genotyped with Diversity Array Technologies single nucleotide polymorphisms (SNPs) markers. A multi-locus genome-wide association study (GWAS) revealed 62 quantitative trait nucleotides (QTNs) associated with FAW and MW resistance traits on all 10 maize chromosomes, of which, 47 and 31 were discovered at stringent Bonferroni genome-wide significance level of 0.05 and 0.01, respectively, and located within or close to multiple-insect resistance genomic regions (MIRGRs) concerning FAW, SB, and MW. Sixteen QTNs influenced multiple-traits of which six were associated with resistance to both FAW and MW suggesting a pleiotropic genetic control. Functional prioritization of candidate genes (CGs) located within 10-30kb of the QTNs revealed 64 putative GWAS-based CGs (GbCGs) showing evidence of involvement in plant defense mechanisms. Only one GbCG was associated with each of five of the six combined-resistance QTNs, thus, reinforcing the pleiotropy hypothesis. In addition, through In-silico co-functional network inferences, an additional 107 Network-based CGs (NbCGs), biologically connected to the 64 GbCGs, differentially expressed under biotic or abiotic stress were revealed within MIRGRs. The provided multiple-insect resistance physical map should contribute to the development of combined-insect resistance in maize.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

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.

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

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.

Bartonella species, intracellular parasitic zoonotic pathogens, has drawn increasing attention for their diverse host range and associated human diseases. This study investigates Bartonella infection in small mammals in Yunnan Province, China, focusing on tissue tropism. 333 small mammals were sampled from 13 species, 3 orders, 4 families, and 4 genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified 30, 10, and 5 strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in the Episoriculus leucops (GS136). Tissue distribution analysis revealed varied copy numbers across different tissues, with the highest load in spleen. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting its broad tissue tropism in small mammals.

Preventive Maintenance (PM) is a periodic maintenance strategy, which has great results for devices in extending their life, increasing productivity, and most importantly, help avoid unexpected breakdowns and their costly consequence. A preventive maintenance scheduling (PMS) is determining the time for carrying out PM, and it represents a sensitive issue in terms of impact on production if the time for the PM process is not optimally distributed. In this study, hybrid heuristic methods were used to solve the PMS problem, as genetic algorithm and Tabu research were adopted. The optimal solution was reached in a short time compared to previous studies in which optimal methods were used, integer programming and nonlinear integer programming. Also, sensitivity analysis was applied to measure the robustness and strength of the method used, where an optimal solution was obtained for all experiments and in record time. This method can be used for power plants in privet or public sectors, to generate an optimal PMS, to save money, and to avoid water or electricity cuts.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

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.

Amid the swift progression of the global automobile industry, the aspiration for lightweight vehicle design has surfaced as a crucial approach to boost fuel efficiency and curtail environmental impact. The objective of this study revolves around achieving holistic optimization of vehicle structure via detailed scrutiny of vehicle process characteristics, amalgamated with a Back Propagation neural network (BPNN) optimized by a genetic algorithm (GA) and a topology optimization (TO) method.The process initiates with an examination of the vehicle's technical characteristics, succeeded by an optimization protocol that couples GA with BPNN. This exhaustive optimization procedure derives the best-fit values of design parameters and identifies the globally optimal lightweight design approach. Subsequently, a comprehensive structural optimization is actualized by modifying the topological distribution of the structure.A simulation experiment of the conceptual car body beam skeleton is conducted as a conclusive step, and the anti-collision capacity of the car body beam skeleton is assessed by measuring deformation intrusion. The findings reveal that in the vehicle topology optimization, a comparative analysis of pre and post-optimization results indicates an improved topological density across diverse sections. The topological density of the vehicle's frontal structure escalates from 0.75 to 0.8. Following optimization, the stiffness assessment records a marginal increase (within the range of 0.02–0.05), implying that the lightweight design does not compromise the general rigidity of the structure.The optimized body structure manifests superior crashworthiness in the crash test: the deformation intrusion diminishes by 27% in front-end collisions. In side impacts, the deformation and intrusion at critical points are reduced by 13.15% to 10% respectively. The comprehensive method proposed herein proves to be an efficient strategy to actualize the lightweight design of vehicles.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Obtaining a genetic diagnosis of a primary mitochondrial disease (PMD) is often framed as a diagnostic odyssey. Yet, even after receiving a diagnosis, parents of affected children experience ongoing therapeutic and prognostic uncertainty, and considerable psychosocial challenges. Semi-structured interviews (N= 24) were conducted with parents of 13 children (aged 2-19 years) with a genetically confirmed PMD. Paternal (N=11) and maternal (N=13) perspectives were obtained, and thematic analysis performed on all interviews. A genetic diagnosis was valuable and empowering for parents, despite eliciting varied emotional responses. While the diagnosis helped focus management decisions, families often felt overwhelmed and unsupported in navigating the healthcare system. Most parents reported a serious impact on their romantic relationship. The sources of social support varied with a preference for established friendship and family support networks over disease-specific community support groups. Most parents favored prenatal genetic testing in the event of a future pregnancy. This study provides insight into the lived experiences of parents after a genetic diagnosis of PMD in their children. The findings draw awareness to supportive care needs and highlight important gaps that should be addressed to ensure that parents feel supported within a holistic framework of management for PMDs.

Toxoplasmosis is a zoonosis of warm-blooded animals, affecting also humans, caused by Toxo-plasma gondii, an obligate intracellular parasite with a complex biological cycle. Toxoplasmosis is considered a re-emerging zoonosis and an important public health threat, also for the absence, up to now, of efficient vaccines and preventive measures. Sources of transmission to humans are environmental or food-borne, mainly through the consumption of raw and undercooked meat, predominantly of Sus scrofa, considered highly susceptible to T. gondii. Mainly in the last dec-ades, an effective strategy to counter animal infectious diseases was based on the discovery of resistance immuno-genetic markers, possibly to be used for association studies between geno-typic and phenotypic traits and consequently in Marker Assisted Selection. Until now, this gen-otyping approach has never been adopted for T. gondii infection, so this study aimed, for the first time, to fill this gap. In particular, pigs, reared in different farms of Central Italy, were serologically characterized by an ELISA assay performed on diaphragm meat juice. Out of 179 tested animals, 98 resulted seropositive (54.74%), 57 seronegative (31.84%) and 24 doubtful (10.6%), underlining a possible re-emerging diffusion of this protozoan in the investigated areas. Atten-tion was firstly focused on IL-18 gene, encoding for a pro-inflammatory cytokine that plays a key role starting from the upstream steps of the immunity pathway towards T. gondii. A RT-PCR assay followed by Sanger sequencing of IL-18 cDNA was de novo developed. For this interleukin, at this stage, genetic analysis has not highlighted significant polymorphic variations compared to the reference sequence, except for a seropositive animal. However, the outcomes of this pre-liminary innovative study will be investigated in depth analyzing other relevant genetic re-gions and other target genes.

Grain quality, cooking quality and nutritional quality traits are some of the major attributes that enhance uptake and utilisation of improved cowpea varieties. Therefore, there is need for a better understanding of the genetic variation and inter-relationships among these quality traits in cowpea to integrate them in cowpea breeding programs. The study was conducted to determine genetic variability among 306 cowpea genotypes for grain quality, cooking quality and nutritional quality traits and to understand the interrelationships among these traits for exploitation in breeding programs. The results showed highly significant differences (P

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

Apple latent spherical virus (ALSV) is widely used as a virus-induced gene silencing (VIGS) vector for function genome study. However, the application of ALSV in soybean is limited by the resistance of many varieties. In this study, the genetic loci linked to the resistance of a resistant soybean variety Heinong 84 was mapped by high-throughput sequencing‒Bulk Segregation Analysis (HTS‒BSA) using a hybrid population crossed from Heinong 84 and a susceptible variety Zhonghuang 13. Results showed that the resistance of Heinong 84 to ALSV is controlled by two genetic loci located on chromosome 2 and 11, respectively. Cleaved amplified polymorphic sequences (CAPS) markers were developed for identification and genotyping. Inheritance and biochemical analyses suggest that the resistance locus on chromosome 2 plays a dominant dose-dependent role, while the other locus contributes a secondary role in resisting ALSV. The resistance locus on chromosome 2 might encode a protein that can directly inhibit viral proliferation, while the secondary resistance locus on chromosome 11 may encode a host factor required for viral proliferation. Together, these data reveal novel insights on the resistance mechanism of Heinong 84 to ALSV, which will benefit for the application of ALSV as a VIGS vector.

Populational aging is marked by chronic non-communicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarity, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

Cassava (Manihot esculenta Crantz), domesticated in the Amazonian region of South America, presents an important diversity in Ecuador, where it is a main staple food; however, only few Ecuadorian cassava accessions have been included in international molecular assessments. The purpose of this study was to apply suitable cassava mi-crosatellites to characterize the genetic variability of the Ecuadorian cassava collection composed mainly of local landraces from the Coast, Andes and Amazonia regions. The use of microsatellite markers allowed the determination of the genetic diversity of the collection. Seven selected SSR primers, permitted to identify homozygous and hetero-zygous materials within the cassava collection of 133 accessions. The loci presented an average genetic diversity value of 0.7 and an average PIC value of 0.67, which is con-sidered high. Low number of duplicates (8.8%) were identified in the Ecuadorian col-lection which is not fully duplicated at CIAT. Currently, a wide range of cassava diver-sity is still cultivated in multi-crop agro-ecosystem, mainly in the Coast and Amazo-nian regions. Especially in the Amazonian region, due to important cultural uses of cassava by local ethnic communities, more in depth studies in the region could unveil the genetic diversity present in situ today.

The weight coefficients of the diaphragm spring depend on experiences in the traditional optimization. However, this method not only cannot guarantee the optimal solution but it is also not universal. Therefore, a new optimization target function is proposed. The new function takes the minimum of average compress force changing of the spring and the minimum force of the separation as total objectives. Based on the optimization function, the result of the clutch diaphragm spring in a car is analyzed by the non-dominated sorting genetic algorithm (NSGA-II) and the solution set of Pareto is obtained. The results show that the pressing force of the diaphragm spring is improved by 4.09%by the new algorithmand the steering separation force is improved by 6.55%, which has better stability and steering portability. The problem of the weight coefficient in the traditional empirical design is solved. The pressing force of the optimized diaphragm spring varied slightly during the abrasion range of the friction film, and the manipulation became remarkably light.

Gibberella ear rot (GER) caused by Fusarium graminearum (teleomorph Gibberella zeae) is one of the most destructive diseases in maize that severely reduces grain yield and contaminates several potential mycotoxins. However, few efforts had been devoted to dissect the genetic basis of maize GER resistance. In the present study, a genome-wide association study (GWAS) was conducted in a maize association panel consisting of 303 diverse inbred lines. The phenotypes of GER severity were evaluated using kernel bioassay across multiple time points in the laboratory. Then, three models including fixed and random model circulating probability unification model (FarmCPU), general linear model (GLM) and mixed linear model (MLM), were conducted simultaneously in GWAS to identify single-nucleotide polymorphisms (SNPs) significantly associated with GER resistance. A total of four individual significant association SNPs with the phenotypic variation explained (PVE) ranging from 3.51 to 6.42% were obtained. Interestingly, the peak SNP (PUT-163a-71443302-3341) with the greatest PVE value, was co-localized in all models. Subsequently, 12 putative genes were captured from the peak SNP that several of these genes were directly or indirectly involved in disease resistance. Overall, these findings contribute to understand the complex plant-pathogen interactions in maize GER resistance. The regions and genes identified herein provide a list of candidate targets for further investigation, in addition to the kernel bioassay that can be used for evaluating and selecting elite germplasm resources with GER resistance in maize.

Atopic dermatitis (AD) is a chronic inflammatory disorder presenting a dysregulated immune response and derangement of the epidermal barrier lipids. The Th2-type cytokines interleukin IL-4 and IL-13 play a prominent role in AD by activating the Janus Kinase/Signal Transduction and Activator of Transcription (JAK/STAT) intracellular signal axis. This study aimed to investigate the role of JAK/STAT in the lipid perturbations induced by Th2 signaling in 3D-epidermal equivalents. We used tofacitinib, a low-molecular-mass JAK inhibitor, to screen for the JAK/STAT-mediated deregulation of lipid metabolism. Th2 cytokines decreased the expression of elongases 1, 3, and 4, and serine-palmitoyl-transferase and increased that of sphingolipid delta(4)-desaturase, and carbonic anhydrase 2. Th2 cytokines inhibited the synthesis of palmitate and caused a depletion of triglycerides. This depletion was associated with altered PC profiles and fatty acid (FA) metabolism. Overall, the ceramide profiles were minimally affected. Except for most sphingolipids and very long chain FAs, the effects of Th2 on lipid pathways were reversed by co-treatment with tofacitinib. An increase in the mRNA levels of CPT1A and ACAT1, reduced by tofacitinib, suggests that Th2 cytokines promote FA beta-oxidation. In conclusion, pharmacological inhibition of JAK/STAT activation prevents the lipid disruption caused by halted homeostasis of FA metabolism.

The paper provides a discussion on the results of studies of the effect exerted by combined degradation factors typical of four types of wear: abrasion, impact-abrasion, tribocorrosion, and impact-abrasion-corrosion, conducted for chain wheels made of Ni-Cu alloyed Austempered Ductile Iron. The studies consisted in determining the content of retained austenite in the structure of the cast irons in question, establishing the measures of wear following wear testing, and identifying basic surface degradation mechanisms observed in the chain wheels tested following multifactorial wear processes. The chain wheels made of ADI were found to have sustained the greatest damage under the impact-abrasion-corrosion (three-factor) wear scenario, while the wear was least advanced in the abrasion (one-factor) wear case. Another observation derived from the studies is that the combined effect of dynamic forces, corrosion, and quartz sand-based abrasives causes increased surface degradation in the cast iron grades taken into consideration compared to processes characterised by a reduced number of degradation factors (i.e. one- or two-factor wear processes). Additional hardness tests and XRD analyses have revealed a distinctive effect attributable to combined degradation factors on the surface hardness increase value and implied that bench testing was followed by phase transition.

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration-resistance is often developed during the course of treatment, though its influences require further understanding. This study explores the human microbiome for its implications in castration-resistance and metastasis in prostate cancer. RNA sequencing data was downloaded for bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These sequences were mapped to bacterial sequences to yield species-level abundance approximations. Numerous species were found to correlate to the expression of known markers of castration-resistance, including AR, PI3K, and AKT. Castration-resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for relation to these species. EGFR and SLC3A2 were widely downregulated with greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration-resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of prostate cancer, allowing for needed improvement in the treatment of this disease.

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

Evidence suggests that COVID-19 infection can cause lasting health consequences. Multidiscipli-nary rehabilitation services have been recommended to reduce the sequalae. However, the effec-tiveness of physical exercise interventions remains insufficiently documented. The aim of this study was to develop and implement a specific and well tolerated protocol-based, intervention to reduce muscle weakness in older adults impacted by COVID-19. Forty six older adults random-ized into Intervention and Control Groups. Isometric and isokinetic strength assessments were conducted for selected muscle groups using JBA Staniak® torquemeter and Biodex System 3 dy-namometer. Functional abilities were evaluated with the Time Up and Go test and Chair Stand Tests. Men in intervention group demonstrated a significant improvement in static conditions for knee flexors (KF), trunk extensors (TE) and trunk flexors (TF) and in dynamic conditions for knee extensors (KE). Women in intervention group showed significant improvement in static condition for EF, KF, TE and TF and in dynamic for a KE and for a KF. The interaction GROUP x TESTING SESSION was significant for Chair test (s) and Chair test (n). Our results demonstrate the effec-tiveness of a well-tolerated, protocol-based approach that can be used to diminish long lasting functional deficits in post-covid survivors.

In the world's first pig-to-human cardiac xenotransplant, the elevated levels of porcine cytomeg-alovirus (PCMV) are considered key factors contributing to patient mortality. This has renewed attention to PCMV, a virus widely prevalent in pigs. Currently, there are no effective drugs or vaccines targeting PCMV, and its high detection difficulty poses challenges for prevention and control research. In this study, antiviral small hairpin RNA (shRNA) was selected and inserted into the Rosa26 and miR-17-92 loci of pigs via a CRISPR/Cas9-mediated knock-in strategy. Further in vitro viral challenge experiments demonstrated that these genetically edited pig cells could effec-tively limit PCMV replication. Through this process, we constructed a PCMV-infected cell model, validated partial viral interference sites, enhanced gene knock-in efficiency, performed gene editing at two different gene loci, and ultimately demonstrated that RNA interference (RNAi) technology combined with CRISPR/Cas9 has the potential to generate pig cells with enhanced antiviral infec-tion capabilities. This opens up possibilities for the future production of pig populations with anti-viral functionalities.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

Vancomycin is one of the ‘last-line’ classes of antibiotics used in the treatment of life-threatening infections caused by Gram-positive bacteria. Even though vancomycin was discovered in 1950s it was widely used after 1980s for the treatment of infections caused by methicillin-resistant Staphylococci as prevalence of such strains were increased. However, currently it is evident that vancomycin resistant Staphylococcusaureusandvancomycin-resistant Enterococci have been developed as a result of various reasons including use of avaparcin, which is an analog of vancomycin, as feed additive in livestock. In present day context, more attention should be paid on prevention of emergence of resistance for the antibiotics in order to keep antibiotics effective. In order to prevent emergence of resistance, proper guidance for the responsible use of antimicrobials is indispensable. Therefore, almost all stakeholders who use antibiotics should have in depth understanding on the antibiotic they use. As such, it is imperative to be aware of the important aspects of vancomycin. In the present review, efforts have been made to discussthe pharmacokinetics and pharmacodynamics, indications, emergence of resistance, control of resistance, adverse effects and alternative therapy for vancomycin.

In this work we looked for a stable and accurate procedure to perform feature selection in datasets with a much higher number of predictors than individuals, as in Genome-Wide Association Studies. Due to the instability in feature selection when many potential predictors are measured, a variable selection procedure is proposed that combines several replications of shrinkage regression models. A weighted formulation is used to define the final predictors. The procedure is applied to investigate Single Nucleotide Polymorphisms (SNPs) predictors associated to Alzheimer’s disease in the Alzheimer’s disease Neuroimaging Initiative (ADNI) dataset. Two data scenarios are investigated: one considering only the set of SNPs and another with the covariates age, sex, educational level and APOE4 genotype. The SNP rs2075650 and the APOE4 genotype are given as risk factors for AD, which is in line with the literature, and other four new SNPs are pointed, opening new hypotheses for in vivo analyses. These experiments demonstrate the potential of the new method for stable feature selection.

Contrary to previous belief, mutation frequency also depends on how essential a gene is. Mutation frequency is substantially lower in the coding regions of essential genes and higher in less essential genes. Even though the mutation bias based on gene essentiality is incapable of invalidating Darwinism, this bias certainly added a rather unsubtle obstacle to it by contradicting a paradigm that was widely held: that mutations are random in the sense of being independent of their function for the organism. The reason this bias occurs is currently unknown. Here, I present the theoretical solution of why genetic mutations also depend on whether the gene is more or less essential. My theory is that each gene or epigene has its own level of resistance to entropic elevation, something directly proportional to the frequency of its expression. The more a gene is expressed, the higher is its resistance to entropic elevation and vice versa. For genetic information to be conserved instead of suffering mutation, a relevant factor is also the frequency of its expression. The energy expenditure directed to a gene of current utility engenders resistance to entropic elevation of the information encoded in that gene, as energy enables not only the existence of information but also its conservation. My theory—which is based on fundamental physics and contains predictions that can be empirically tested—solves a crucial problem in evolutionary biology and genetics; if I am right, I will have established a biological law. Finally, my aim here is also to provide a substantial advance in knowledge about the relationship between information, genetics, and thermodynamics.

Extensive genome structure variation, such as copy number variations (CNVs) and presence/absence variations, is the basis for the remarkable maize genetic diversity; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene, ZmLOX5, leads to increased resistance of maize to herbivory by fall armyworms (FAW). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into the herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either 2, 1 or 0 copies of the Yu796-2×LOX5 locus in the B73 background by six back crosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed enhanced drought tolerance likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into the productive, but susceptible, crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups, as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (P < 0.05). Cashmere production was higher in goats aged 2-4 years compared to those aged 5-7 years (P < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2-4 years) having a higher population than those aged 5 – 7 years (P < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (P < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (P < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (P < 0.05). Interestingly, the skin antioxidant capacity and oxidative damage exhibited significant positive and negative correlations, respectively, with the population of active secondary hair follicles (P < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress.

Soil-borne Trichoderma spp. have been extensively studied for their biocontrol activities against pathogens and growth promotion ability with plants. However, the beneficial effect of Trichoderma on inducing resistance against insect herbivores has been considered only recently. Among diverse Trichoderma species, consistent with previous reports, we showed that root colonization by T. virens triggered induced systemic resistance (ISR) to leaf-infecting fungal pathogens. Whether T. virens induces ISR to insect pests has not been tested before. In this study, we investigated whether T. virens affects jasmonic acid (JA) biosynthesis and defense against fall armyworm (FAW) and western corn rootworm (WCR). Unexpectedly, the results showed that T. virens colonization of maize seedlings grown in autoclaved soil suppressed wound-induced production of JA, resulting in reduced resistance to FAW. Similarly, the bacterial endophyte Pseudomonas chlororaphis 30-84 suppressed systemic resistance to FAW due to reduced JA. Further comparative analyses of the systemic effects of these endophytes when applied into sterile or non-sterile field soil showed that both T. virens and P. chlororaphis 30-84 triggered ISR against hemibiotrophic fungal pathogen Colletotrichum graminicola in both soil conditions, but only suppressed resistance to FAW in sterile soil. In contrast to the effect on FAW defense, T. virens colonization of maize roots suppressed WCR larvae survival and weight gain. This is the first report suggesting the potential role of T. virens as a biocontrol agent against WCR.

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

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

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.

Pervasive purifying selection on non-synonymous substitutions is a hallmark of papillomavirus genome history. Whereas the role of selection on, and drift of, non-coding DNA elements on HPV diversification is poorly understood. More than a thousand complete genomes representing Alphapapillomavirus types, lineages and SNP variants were examined phylogenetically and interrogated for the number and position of non-coding DNA sequence motifs using Principal Components Analyses, Ancestral State Reconstructions and Phylogenetic Independent Contrasts. For anciently diverged Alphapapillomavirus types, composition of the 4 nucleotides (A,C,G,T), codon usage, trimer usage and 13 established non-coding DNA sequence motifs revealed phylogenetic clusters consistent with genetic drift. Ancestral state reconstruction and Phylogenetic Independent Contrasts revealed ancient genome alterations, particularly for CpG and APOBEC3 motifs. Each evolutionary analytical method we performed supports the unanticipated conclusion that genetic drift and different evolutionary drivers have structured Alphapapillomavirus genomes in distinct ways during successive epochs, even extending to differences in more recently formed variant lineages

Recent technological advancements in conservation genetics and genomics have resulted in diverse tools for aiding conservation of species. The precision and resolution of high throughput sequencing technologies provide valuable insights to aid conservation decisions, but these technologies are often financially unfeasible or unavailable in resource constrained countries. Inter-Simple Sequence Repeat (ISSR) markers, when combined with sensitive automated detection systems, provide a simple, cheap means to investigate genetic diversity and discriminate closely related species. Here we apply this technology to assess genetic diversity and taxonomic delimitation in the Encephalartos eugene-maraisii species complex, a highly threatened, taxonomically dubious group of cycads in South Africa. Silica dried cycad leaflets were extracted using the Oktopure robot employing Sbeadex chemistry and amplified with fluorescently tagged ISSR primers. Band presence was scored with an ABI 3130 genetic sequencer under three different fluorescence cut-off values. Phenetic analyses were performed in NTSYS software while Bayesian analysis was performed in STRUCTURE, and haplotype network analysis, AMOVA and Tajima’s D statistic was computed with PopART. Our analyses support taxonomic singularity of E. dyerianus, E. dolomiticus and E. eugene-maraisii. Relationships between E. nubimontanus and E. cupidus remain uncertain. E. middelburgensis samples showed no clustering but had poor amplification success. This study demonstrated the suitability of automated ISSR fingerprinting as a method for plant conservation studies, especially in resource-constrained countries.

Fusarium wilt of banana is a devastating disease that has decimated banana production worldwide. Host resistance to Fusarium oxysporum f. sp. cubense (Foc), the causal agent of this disease, is genetically dissected in this study using two Musa acuminata ssp. malaccensis segregating populations segregating for Foc Tropical (TR4) and Subtropical (STR4) race 4 resistance. Marker loci and trait association using 11 SNP-based PCR markers allowed the candidate region to be delimited to a 12.9 cM genetic interval corresponding to a 959 kb region on Chromosome 3 of ‘DH-Pahang’ reference assembly v4. Within this region, there is a cluster of pattern recognition receptors, namely leucine rich repeat ectodomain containing receptor-like protein kinases, cysteine-rich cell wall associated protein kinases, and leaf rust 10 disease-resistance locus receptor-like proteins positioned in an interspersed arrangement. Their transcript levels were rapidly upregulated in the resistant but not in susceptible F2 progenies at the onset of infection. This suggests that one or several of these genes may control resistance at this locus. To confirm the segregation of single-gene resistance, we generated an inter-cross between the resistant parent ‘Ma850’ and a susceptible line ‘Ma848’, to show that the STR4 resistance co-segregated with marker ‘28820’ at this locus. Finally, an informative SNP marker 29730 allowed the locus specific resistance to be assessed in a collection of diploid and polyploid banana plants. Out of the 60 lines screened, 22 lines were predicted to carry resistance at this locus, including lines known to be TR4 resistant, such as ‘Pahang’, ‘SH-3362’, ‘SH-3217’, ‘Ma-ITC0250’, and ‘DH-Pahang/CIRAD 930’. Additional screening in the International Institute for Tropical Agriculture’s collection suggests that the dominant allele is common among in the elite ‘Matooke’ NARITA hybrids, as well as in other triploid or tetraploid hybrids derived from East African highland bananas. Fine-mapping and candidate gene identification will allow characterization of molecular mechanisms underlying TR4 resistance. The markers developed in this study can now aid the marker-assisted selection of TR4 resistance in breeding programs around the world.

Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p &lt; 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.

Genetic engineering has become an essential element in developing climate-resilient crops and environmental sustainable solutions to respond to the increasing need for global food security. Genome editing using CRISPR/Cas [Clustered regulatory interspaced short palindromic repeat (CRISPR)-associated protein (Cas)] technology is being applied to a variety of organisms, including plants. This technique has become popular because of its high specificity, effectiveness, and low production cost. Therefore, this technology has the potential to revolutionize agriculture and contribute to global food security. Over the past few years, increasing efforts have been seen in its application in developing higher-yielding, nutrition rich, disease resistant, stress-tolerant “crops” fruits and vegetables. Cas proteins such as Cas9, Cas12, Cas13, and Cas14, among others, have distinct architectures and have been used to create new genetic tools that improve features that are important for agriculture. The versatility of Cas has accelerated genomic analysis and facilitated the use of CRISPR/Cas to manipulate and alter nucleic acid sequences in cells of different organisms. This review provides the evolution of CRISPR technology exploring its mechanisms and contrasting it with traditional breeding and transgenic approaches to improve different stress tolerance. We have also discussed the CRISPR/Cas system and explored three Cas proteins that are currently known to exist: Cas12, Cas13, and Cas14 and their potential to generate foreign DNA free or non-transgenic crops that could be easily regulated for commercialization in most countries.

To estimate the progressive collapse resistance capacity of a multi-column frame tube structure with the assembled truss beam composite floor (ATBCF), the pushdown analysis, and the nonlinear dynamic analysis as well, are conducted for such a structure by using the alternate load path (ALP) method. The bearing capacities of the remaining structures at three different work conditions, which are the side middle column failure, the edge middle column failure, and the corner column failure, are individually studied, and the collapse mechanism for the remaining structures is analyzed from the aspects of the internal force redistribution and the failure mode of the second defense line. Simultaneously, the influence of the column failure time on the dynamic response of the remaining structure and the dynamic amplification coefficient are discussed. The results show that the residual bearing capacity of the remaining structure with the bottom corner column failure is higher than that of the one with the side or edge middle column failure, while the latter has a stronger plastic deformation capacity. When the ALP method is adopted to operate the progressive collapse analysis, it is reasonable to take the column failure time as 0.1 times of the first-order vertical vibration period of the remaining structure, and it is suitable to set the dynamic amplification coefficient as of 2.0, which is the ratio of the maximum dynamic displacement to the static displacement of the remaining structure under the transient loading condition.

The dynamic resistance is an important parameter in flux pumping. It is simple to calculate in slab geometry but more complex in tapes. In this paper another simple geometry is analysed which is a wire loop. To do this it is essential to make clear what is meant by the term 'voltage', which is ambiguous when there are alternating magnetic fields present. The term can be used if it refers to the EMF along a specified path. However this means that results are dependent on how the voltage leads are attached. If the n value of the V-I characteristic is large simple analytic expressions can be obtained. This will be referred to as the 'Bean' model solution. A more exact approach uses Faraday's law to derive a differential equation which is solved and compared with the Bean model. The dynamic resistance of the loop can be used to drive a flux pump of the type proposed by Geng and Coombs [4] and again simple expressions can be obtained for the performance. If the load is of high inductance L2 and the loop has an inductance L1 then the load current increases exponentially with a characteristic number of cycles L2/L1. The final current can be close to the critical value.

Psoriasis is considered an immune-mediated disease involving the innate and adaptative immune system triggered by environmental risk factors in genetically susceptible individuals. However, its physiopathology is not fully understood yet. Recent technological advances, specially genome and epigenome-wide studies, have allowed a more sensitive study of the genetic and epigenetic mechanisms, allowing an enhanced understanding of its physiopathology and facilitating the development of new drugs. In this review, we aim to summarize the current evidence on genetic and epigenetic mechanisms of psoriasis.

This document summarizes the evidence currently available about the effects of the anesthetic agents and techniques used in primary cancer surgery and long-term oncologic outcomes, and the biomolecular mechanisms involved in their interaction..

Nowadays genetic algorithm (GA) is greatly used in engineering pedagogy as an adaptive technique to learn and solve complex problems and issues. It is a meta-heuristic approach that is used to solve hybrid computation challenges. GA utilizes selection, crossover, and mutation operators to effectively manage the searching system strategy. This algorithm is derived from natural selection and genetics concepts. GA is an intelligent use of random search supported with historical data to contribute the search in an area of the improved outcome within a coverage framework. Such algorithms are widely used for maintaining high-quality reactions to optimize issues and problems investigation. These techniques are recognized to be somewhat of a statistical investigation process to search for a suitable solution or prevent an accurate strategy for challenges in optimization or searches. These techniques have been produced from natural selection or genetics principles. For random testing, historical information is provided with intelligent enslavement to continue moving the search out from the area of improved features for processing of the outcomes. It is a category of heuristics of evolutionary history using behavioral science-influenced methods like an annuity, gene, preference, or combination (sometimes refers to as hybridization). This method seemed to be a valuable tool to find solutions for problems optimization. In this paper, the author has explored the GAs, its role in engineering pedagogies, and the emerging areas where it is using, and its implementation.

Genetic and sporadic forms of tauopathies, the most prevalent of which is Alzheimer’s Disease, are a scourge of the aging society, and in case of genetic forms, can also affect children and young adults. All tauopathies share ectopic expression, mislocalization, or aggregation of the microtubule associated protein TAU, encoded by the MAPT gene. As TAU is a neuronal protein widely expressed in the CNS, the overwhelming majority of tauopathies are neurological disorders. They are characterized by cognitive dysfunction often leading to dementia, and are frequently accompanied by movement abnormalities such as parkinsonism. Tauopathies can lead to severe neurological deficits and premature death. For some tauopathies there is a clear genetic cause and/ or an epigenetic contribution. However, for several others the disease etiology is unclear, with few tauopathies being environmentally triggered. Here we review current knowledge of tauopathies listing known genetic and important sporadic forms of this disease. Further, we discuss how DNA methylation as a major epigenetic mechanism emerges to be involved in the disease pathophysiology of Alzheimer’s, and related genetic and non-genetic tauopathies. Finally, we debate the application of epigenetic signatures in peripheral blood samples as diagnostic tool and usage of epigenetic therapy strategies for these diseases.

The medicinal plant Abrus precatorius L. was traditionally used in Siddha and Ayurvedic systems of medicine in India. The Indian centre of origin holds vast variability for its seed color. The objective of this study was to assess the total monomeric anthocyanin, flavonol, antioxidative potential, protein content and ash content among the accessions. A total of 99 accessions conserved in the Indian National Genebank were used in this study. The method used for the estimation of total monomeric anthocyanin, flavonol, antioxidative potential, protein content and ash content was pH differential method, Oomah method, Ferric Reducing Antioxidant Potential, Dumas method and gravimetric method respectively. The completely black colored accession was recorded with highest total monomeric anthocyanin (51.95 mg / 100 g of cyanidin 3-glucoside equivalent) and flavonol content (66.41 mg/g of quercetin equivalent). Red + black colored accessions have recorded the maximum value with respect to antioxidants (14.18 mg/g of gallic acid equivalent). Highest amount of protein content was found in a completely white colored accession (20.67%) and maximum ash content was recorded in red + black seed colored accession (4.01%). The promising accessions identified can be used by pharmaceutical companies in drug development and in curing degenerative diseases.

Background Cytomegalovirus (CMV) is a major pathogen that cause remarkable rate of morbidity and mortality, especially in immunocompromised patients. It is important to find risk factors associated with CMV viremia. We studied the differences in CMV seropositivity in relation to liver function biomarkers in male and female Saudi population in an attempt to understand the variation in the CMV seroprevalence with sex and find the risk factor to develop liver dysfunction or hepatocellular carcinoma. Material and subjects: The CMV- IgG and IgM were screened in serum samples of 150 non- A-G hepatities patients with elevation of liver profiles (ALT, AST, ALP and GGT) and categorized as males and females. Samples were collected from different general hospitals and polyclinic in KSA from March 2014 to June 2015. A correlation between CMV seropositivity measured with both antibodies and liver enzymes were tested. Receiver operating characteristics (ROC) analysis and multiple regressions were done for the obtained data. Results: Our study shows that females had much higher IgG and IgM compared to age-matching males. A significant correlation between both antibodies and liver enzymes (AST, ALT) was recorded. Less significant correlation of both IgG and IgM with GGT was also observed. Receiver operating characteristics (ROC) analysis revealed that both IgG and IgM can be used as excellent predictive markers for CMV infection as both recorded 100% specificity and sensitivity together with area under the curve of 1 in males and females. Multiple regression analysis ascertain the correlation between both antibodies as dependent variables and liver enzymes as independent variables with ALT being the most affected enzyme with CMV seropositivity especially in females. Conclusion:he data discussed above This study shows that CMV is capable of initiating and accelerating liver dysfunction in both sexes. The high seroprevalence in females at reproductive age is especially important as they can transmit the virus to their developing fetus. Prevention of CMV infection in young girls 11-14 years old, through counseling on hygiene or possible future vaccination, may lead to a decrease of congenital CMV infections with the concomitant risk of developing liver dysfunction or hepatocellular carcinoma. Keywords: Cytomegalovirus, Alanine transaminase, Aspartate transaminase Alkaline phosphatase, γ-Glutamyltranspeptidase, liver function.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Skin cancer is a prevalent and heterogenous disease with several subtypes, such as melanoma, basal cell carcinoma, and squamous cell carcinoma. Among them, melanoma is the most aggressive subtype, with a higher propensity to spread compared to most solid tumors. The application of OMICS approaches has revolutionized the field of melanoma research by providing comprehensive insights into the molecular alterations and biological processes underlying melanoma development and progression. This review aims to offer an overview of melanoma biology, covering its transition from primary to malignant melanoma, as well as the key genes and pathways involved in the initiation and progression of this disease. Utilizing online databases, we extensively explored the general expression profile of genes, identified the most frequently altered genes, and gene mutations, and examined genetic alterations responsible for drug resistance. Additionally, we studied the mechanisms responsible for immune checkpoint inhibitors resistance in melanoma.

Information molecules of DNA and RNA should obey principles of quantum mechanics where unitary operators in form of unitary matrices have key meanings. Unitary matrices are the basis of calculations in quantum computers. This article presents some author's results, which show that matrix forms of the representation of structured systems of molecular-genetic alphabets can be considered as sets of sparse unitary matrices related with phenomenologic features of the degeneracy of the genetic code. These sparse unitary matrices have orthogonal systems of functions in their rows and columns. A complementarity exists among some unitary genetic matrices in relation each other. Decompositions of numeric genetic matrices into sets of sparse unitary matrices are connected with the logical operation of modulo-2 addition used in quantum computers as well. Tensor (or Kronecker) families of unitary genetic matrices with their fractal-like properties are also considered. The described results are discussed in the frame of development of quantum-information approaches for modeling genetic systems.

Viroids are known the smallest plant pathogens, and although their genome sequences do not encode proteins, they can cause disease in economically important crops. In order to control viroid diseases and mitigate their damage, genetic resources used for breeding of the viroid-resistant crop have been searched, but the practical resistant trait has not been found in almost all viroid-crop combinations, as well as the tolerant trait. Due to the difficulty in exploiting naturally occurring resistance or tolerance, various effective strategies have been devised to control viroid diseases using non-transforming or transforming techniques. Meanwhile, extensive findings related to viroid resistance and tolerance may lead to confer resistance or tolerance to viroid infection by combining with the recently emerged new technologies (e.g., spray-induced gene silencing and genome-editing technologies), which are believed to be more environmentally viable and acceptable to the general public than previously reported approaches. In particular, some genome-modified crops produced by the latter technology are already on the market. In this review, we comprehensively summarize the current status about investigation of naturally occurring genetic traits for viroid resistance and tolerance, accumulating knowledge about host factors involved in viroid pathogenicity, and various basic technologies developed to try to possible viroid disease control strategies. Furthermore, we discuss prospects and challenges for the achievement of more effective, practical, and sustainable disease control of viroid.

Determining genetic and non-genetic sources of variation in a breed is vital for the formulation of strategies for its conservation and improvement. The present study was aimed at estimating the (co)variance components and genetic parameters of Mecheri sheep by fitting six different animal models in the restricted maximum likelihood method, with a preliminary investigation on the performance of animals for non-genetic sources of variation. A total of 2616 lambs were studied, and varying levels of significance were found for the effect of period, season, parity of dam and birth type on different body weight traits. Direct heritability estimates derived from the best animal model for body weight at birth, 3 months, 6 months, 9 months and 12 months were 0.21, 0.24, 0.10, 0.15 and 0.09, respectively, and maternal heritabilities of the corresponding traits were 0.12, 0.05, 0.04, 0.04 and 0.04, respectively. The genetic correlations between body weight traits were all positive and moderate to strong except for birth weight with the other body weight traits. The significance of non-genetic factors studied in this work demanded a correction to improve the accuracy of the direct selection of lambs for body weight traits. The estimated genetic parameters identified the weaning weight as a selection criterion for the improvement in body weight of Mecheri lambs at different ages. Inbred individuals accounted for approximately 13% of the total population in the Mecheri sheep population studied. There were 877 founders in the population, and the actual effective size of the population was 128.48. The population's mean generation interval was 3.26. The mean inbreeding values ranged from 0.005 to 0.010 across generations. The population's average relatedness ranged from 0.001 to 0.014 across generations. Individual inbreeding was found to be 0.45 per cent for the entire population and 3.4 per cent for the inbred population.

Classical Hodgkin lymphoma (cHL) is a highly curable disease (70-80%), even though long-term toxicities, drug resistance, and predicting clinical responses to therapy are major challenges in cHL treatment. To solve these problems, we characterized two cHL cell lines with acquired resistance to doxorubicin, KM-H2dx and HDLM-2dx (HRSdx), generated from KM-H2 and HDLM-2 cells, respectively. HRSdx cells developed cross-resistance to vinblastine, bendamustin, cisplatin, dacarbazine, gem-citabine, brentuximab vedotin (BV), and γ-radiation. Both HDLM-2 and HDLM-2dx cells had an intrinsic resistance to BV but not to the drug MMAE. HDLM-2dx acquired cross-resistance to caelyx. HRSdx cells had in common: decreased CD71, CD80, CD54, cyt-ROS, HLA-DR, DDR1, CD44; increased Bcl-2, CD58, COX2, CD26, CCR5, invasive capability; increased CCL5, TARC, PGE2, TGF-β, and capability to hijack monocytes. In HRSdx cells, less sensitive to DNA damage and oxidative stress, the efflux drug transporters MDR1 and MRP1 were not up-regulated, and doxorubicin accumulated in cytoplasm rather than in nucleus. Both autophagy inhibitor chloroquine and extracellular vesicles (EVs) release inhibitor GW4869 enhanced doxorubicin activity and counteracted doxorubicin resistance. In conclusion, this study identifies common modulated antigens in HRSdx cells, the associated cross-resistance patterns, and new potential therapeutic options to enhance doxorubicin activity and overcome resistance.

The grooved carpet-shell clam is one of the most economically relevant shellfish species living in the Mediterranean and nearby Atlantic coasts. Previous studies using different types of genetic markers showed a remarkable genetic divergence of the Eastern Mediterranean, Western Mediterranean and Atlantic populations, but important details remained unclear. Here, data from six nuclear introns scored for restriction fragment size polymorphisms in eight populations that have not been studied before have been pooled for the analysis with data scattered through three previous studies, totaling 32 samples from 29 locations. The results show lower levels of heterozygosity, higher mean number of alleles, and alleles with restricted distribution in the Mediterranean populations, suggesting the existence of a large isolated population in the eastern Mediterranean at the middle Pleistocene. The data also confirm the similarity of populations from Tunisia to western Mediterranean populations. Finally, a genetic mosaic is apparent in the Atlantic coasts of the Iberian Peninsula, with a divergence of Rias Baixas populations from more northern populations and Central Portugal populations. The effects of oceanic fronts, seasonal upwellings, river plumes and/or fishery management operations could explain this and other features of the Atlantic populations.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

Globally increasing antibiotic resistance has been connected to the use of antibiotics in medical, veterinary, and agricultural medicine, contributing to the burden of antibiotic resistance in Asia and Europe. The main objective of this study was to correlations of antimicrobial-resistant of various pathogens in three compartments: humans, animals and the environment in India and Germany. A systematic search was carried out in Medline via PubMed, Google Scholar, and science direct, including studies published in 2022. Out of 532 papers, 24 were considered for meta-analysis. This study reveals that in India, β-lactam is highly resistant in animals. Quinolone, on the other hand, was highly resistant in humans. Furthermore, in the environment and integrated studies, aminoglycosides and β-lactams is resistant. While in Germany, a high rate of AMR resistance in all three sectors was reported in β-lactam. However, E. coli was the most frequent pathogen in both countries and is highly resistant to β-lactam, followed by cephalosporin in all the compartments. Monitoring and evaluating antibiotic-sensitivity patterns and developing proper antibiotic regimens may lead to improved outcomes for inhibiting and controlling E. coli infections in various parts of the world.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

Acanthamoeba keratitis (AK) is a severe, rare protozoal infection of the cornea. Acanthamoeba can survive in diverse habitats and at extreme temperatures. AK is mostly seen in contact lens wearers, whose lenses have become contaminated, or a history of water exposure, and in those without contact lens wear, who have experienced recent eye trauma involving contaminated soil or water. Infection usually results in severe eye pain, photophobia, inflammation, and corneal epithelial defects. The pathophysiology of this infection is multifactorial, including the production of cytotoxic proteases by Acanthamoeba that degrades the corneal epithelial basement membrane and induce the death of ocular surface cells, resulting in degradation of the collagen-rich corneal stroma. AK can be prevented by avoiding the risk factors, which include avoiding water contact such as swimming or showering in contact lenses, and wearing protective goggles when working on the land. AK is mostly treated with an antimicrobial therapy of biguanides alone or in combination with diaminidines, although the commercial availability of these medicines is variable. Other than anti-amoeba therapies, targeting host immune pathways in Acanthamoeba disease may lead to the development of vaccines or antibody therapeutics which could transform the management of AK.

The article shows materials to the question about algebraic features of the genetic code and about the dictatorial influence of the DNA and RNA molecules on the whole organism. Presented results testify in favor that the genetic code is an algebraic code related with a wide class of algebraic codes, which are a basis of noise-immune coding of information in communication technologies. Structural features of the genetic systems are associated with hypercomplex double (or hyperbolic) numbers and with bisymmetric doubly stochastic matrices. The received results confirm that represented matrix approaches are effective for modeling genetic phenomena and revealing the interconnections of structures of biological bodies at various levels of their organization. This allows one to think that living organisms are algebraically encoded entities where structures of genetic molecules have the dictatorial influence on inherited structures of the whole organism. New described algebraic approaches and results are discussed.

Impressing discoveries in the field of the genetic code have been described by its researchers by means of the terminology borrowed from linguistics and the theory of communications. Leading experts on structural linguistics believe for a long time already that languages of human dialogue were formed not from an empty place, but they are continuation of genetic language or, anyhow, are closely connected with it, confirming the idea of information commonality of organisms. The aticle continues the theme about a connection of linquistic languages with the genetic language. It describes results of comparative study of long Russian literary texts (novels by L.Tolstoy, F.Dostoevsky, A.Pushkin, etc.) and long sequences of hydrogen bonds in double helixes of DNA of different organisms. Formalisms of quantum informatics are used in modeling some of these results taking into account thoughts of many researches about possible using principles of quantum informatics in organisation of living bodies.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.

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.