The existence of multiple copies of genes is a well-known phenomenon. A gene family is a set of sufficiently similar genes, formed by gene duplication. In earlier works conducted on limited number of completely sequenced and annotated genomes it was found that size of gene family and size of genome are positively correlated. Additionally, it was found that several atypical microbes deviated from the observed general trend. In this study, we reexamined these associations on a larger dataset consisting of 1484 prokaryotic genomes and using several ranking approaches. We applied ranking methods in such a way that genomes with lower number of paralogs would have lower rank. Until now only simple ranking methods were used; we applied the Kemeny optimal aggregation approach as well. Regression and correlation analysis were utilized in order to accurately quantify and characterize the relationships between measures of paralog indices and genome size. In addition, boxplot analysis was employed as a method for outlier detection. We found that, in general, all paralog indexes positively correlate with an increase of genome size. As expected, different groups of atypical prokaryotic genomes were found for different types of paralog quantities.

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.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease (CHD), hypertension, heart failure (HF), cerebrovascular disease, atrial fibrillation (AF), ventricular arrhythmias, and sudden cardiac death (SCD). In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen, and C-reactive protein and others, all of which increase the risk of CVD events. Mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokines dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left ventricular (LV) remodeling and diastolic dysfunction. Natural products of plants, provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discussed the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herbs and plants extracts for the prevention and treatment of CRFs are also reviewed.

Keywords: pelvic ultrasound, follicle number per ovary, FNPO, ovarian volume, PCOM, upper normal limits, referral population

Originating in the Mediterranean, B. oleracea is grown all over the world and is highly valued for its nutritional value and variety in cooking. Its susceptibility to pests, diseases, and environmental stressors, however, poses significant challenges to sustaining consistent crop quality and productivity. The BASIC PENTACYSTEINE gene significantly impacts plant growth and responses to abiotic stresses. Nevertheless, little is known about its precise role and the underlying biological processes in B. oleracea. Eleven BPC genes in B. oleracea were identified by a thorough genome-wide investigation and categorized into three categories according to their structural traits and gene motifs. There were eight different chromosomes on which these BoBPCs were located. Comparative synteny analysis was used to reveal the evolutionary traits of potatoes, Arabidopsis, and B. oleracea. The BoBPC family genes in B. oleracea were found to have specific cis-elements linked to growth, stress responses, and hormone regulation when their promoter regions were studied. Cuticular wax synthesis expression revealed that all BoBZR1 genes, from wild to mutant, expressed at varied amounts in distinct types. Moreover, distinctive BoBPC gene expression patterns were found in the seven distinct tissues that were studied. Our thorough analysis shows that the BoBPC family is widely involved in B. oleracea developmental processes. The present findings provide an established theoretical basis for further exploration into the composition and roles of BoBPC in B. oleracea.

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. Being composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module looks advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated high affinity for target receptors, as revealed by fluorescently labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNT. Thus, this work reveals that MNT’s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

The AREB/ABF (ABA response element binding) proteins in plants are vital for plant stress responses, but the understanding of AREB/ABFs in orchid species, an important traditional medicinal and ornamental plants, is limited. Here, twelve AREB/ABF genes were identified within three orchids’ complete genome and classified into three groups (groups I, II, and III) via a phylogenetic analysis, which was further supported by the analysis of their conserved motifs and gene structures. The cis-elements analysis showed that hormone response elements followed by light and stress responses were widely rich in AREB/ABFs. A prediction analysis of orchid ABRE/ABF-mediated regulatory network was further constructed through cis-regulatory elements (CREs) analysis of their promoter regions and revealed that several transcriptional factor (TF) gene family were abundant as the potential regulators for orchid AREB/ABFs. Expression profile analysis based on public transcriptomic data showed that most AREB/ABF genes have distinct tissue-specific expression patterns in orchid plants. Additionally, DcaABI5 as the homolog of ABA INSENSITIVE 5 (ABI5) from Arabidopsis was selected for further analysis. The results showed that Arabidopsis transgenic overexpressing DcaABI5 could rescue the ABA insensitive phenotype in the mutant abi5. Collectively, these findings will provide valuable information on AREB/ABF genes in orchids.

Abstract: Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22aCre leads to AVM development in the brain and other organs. We have reported that the severity of brain AVM in mice with activin receptor-like kinase 1 (Alk1, an HHT2 causative gene) mutation is correlated with the number of Alk1 negative endothelial cells (ECs). We hypothesized that increase of Eng negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon improved cre (icre), which is more potent in recombination of floxed alleles than the wild type (WT) cre. R26RCreER;Eng^f/f mice that have Rosa promoter driving and tamoxifen (TM) inducible WT cre expression globally and PdgfbiCreER;Eng^f/f that have Pdgfb promoter driving and TM inducible icre expression in ECs were treated with 3 intra-peritoneal injections of TM (2.5 mg/25g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that iCre caused more Eng deletion in the brain indicated by lower level of Eng proteins (p<0.001) and fewer Eng positive ECs (p=0.01) than mice with WT cre. Mice with iCre mediated Eng deletion have more abnormal vessels (p=0.02), CD68⁺ macrophages (p=0.002), and hemorrhage (p=0.04), and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that have not been detected in WT cre mice before. RNAseq analysis showed that 8 out of the 10 top upregulated pathways identified by Gene Ontology (GO) analysis are related to the inflammation. Therefore, increase of Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

Today, polymeric Drug Delivery Systems (DDS) appear as an interesting solution against bacterial resistance, having great advantages such as low toxicity, biocompatibility, and biodegradability. In this work, two polyketones (PK) have been post-functionalized with taurinate (PKT) or sulfanilate (PKSK) and employed as biocompatible carriers for Vancomycin against bacterial infections. Mod-ified PKs were easily prepared by Paal-Knorr reaction and loaded with Vancomycin at variable pH. All polymers were characterized by FT-IR, DSC, TGA, SEM and elemental analysis. Antimicrobial activity was tested against Gram positive Staphylococcus aureus ATCC 25923 and correlated to the different pH used for its loading (between 2.3 and 8.8). Distinctively, minimum inhibitory con-centrations achieved with PKT and PKSK loaded with Vancomycin are similar, 0.23μg/mL and 0.24μg/mL respectively, i.e. six times lower that Vancomycin alone. The use of post-functionalized aliphatic polyketones has thus been demonstrated to be a promising way to obtain very efficient polymeric DDS.

Objective: This study aims to examine CA-125 and miRNAs as biomarkers in endometriosis pathophysiology and their potential roles in clinical diagnostics and prognostics. Methods:We reviewed a variety of studies, including cross-sectional, case-control, and prospective designs, examining a broad spectrum of patient demographics, clinical features, and biomarker (CA-125 and miRNA) expression levels. Results: CA-125 has been reaffirmed as a valuable biomarker in diagnosing and monitoring endometriosis, with its utility enhanced when used alongside other markers. MiRNAs have emerged as promising molecular regulators, offering new avenues for non-invasive diagnostics and a deeper understanding of the disease's pathophysiology. The integration of these biomarkers presents a potential shift towards more personalized and effective diagnostic and therapeutic strategies. Conclusion: Endometriosis presents a significant challenge in women's health, requiring innovative approaches for its management. The convergence of CA-125 and miRNA research represents a promising advance, potentially leading to more accurate diagnostics and personalized treatment. Future research should focus on standardizing methodologies, expanding study cohorts, and integrating findings into clinical practice to fully harness the potential of these biomarkers.

This work explores state-of-the-art approaches for stabilizing an inverted pendulum on a cart system, which has been used for over a century to demonstrate ideas in nonlinear and linear control theory, owing to its simple practical implementation yet complex system dynamics. We introduce energy-based control methods and propose a simple linear controller to quickly force the system to the downward equilibrium before swing-up. By constraining the system to start from a stable equilibrium configuration, the problem of global stability is reduced to ensuring that the system can follow all heteroclinic orbits that start very close to the downward equilibrium. Multiple Lyapunov functions are employed to ensure non-zero tracking, increasing the system's domain of attraction than is achieved by traditional controllers based on a single Lyapunov function. We stabilize our inverted pendulum system in the upright configuration through pole placement using a linear quadratic regulator known for fast settling times and smooth system response and through sliding mode controllers known for their robustness to disturbances and model uncertainties. While sliding mode controllers exhibit faster stabilization of the pendulum angle, they fail to stabilize the cart position in a reasonable amount of time. The paper concludes by suggesting various controller techniques that can enhance the swing-up and stabilization controller architectures, leaving room for future exploration. To facilitate further research and education, an open-source MATLAB simulation code is provided, encapsulating the system dynamics and controller designs. This resource offers flexibility for customization, making it a valuable tool for both researchers and educators working with inverted pendulum systems.

Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder (PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of a SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.

Diacylglycerol kinase (DGK) is a lipid kinase that phosphorylates diacylglycerol (DAG) to generate phosphatidic acid (PA). Based on converting one important signaling molecule (DAG) to another (PA), DGK plays an important role in plant responses to abiotic stress including waterlogging stress. However, no studies have been reported on the characterization of the DGK gene family in the waterlogging-tolerant kiwifruit germplasm, Actinidia valvata Dunn. Here, we identified 18 AvDGK genes in the A. valvata genome. The phylogenetic analysis showed that AvDGKs can be classified into three clusters, and members within the same cluster have similar domain distribution, exon-intron structures and conserved motif compositions. Chromosome localization analysis revealed that all the AvDGK genes are located across 18 different chromosomes. There were 29 duplicated gene pairs in kiwifruit and all had undergone purifying selection during evolution. Promoter cis-element analysis revealed that the cis-elements within AvDGK genes are associated with multiple functions, including phytohormone signal transduction, stress response, and plant growth and development. The expression pattern analyses indicated that AvDGK play an important role in the fruit development and plant response to waterlogging stress. AvDGKs gene family in the tetraploid A. valvata genome might promote PA synthesis and subsequent signal transduction both under short-term and long-term waterlogging stress. These results provide information regarding the structural characteristics and potential function of DGK genes within kiwifruit and lay a fundamental basis for further research into breeding for enhancing the kiwifruit’s tolerance to waterlogging stress.

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.

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

Keywords: Vascular Malformation, Diode Laser, Angioma, Blue light, Conservative

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder, characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGFβ) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discuss recent advances in identifying disease mechanisms, and potential therapeutic targets.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

Background and Objectives: Cancer as the second leading cause of death in the United States poses a huge healthcare burden. Barriers to access to advanced therapies influence the outcome of cancer treatment. In this study, we examined whether insurance types affect the quality of cancer clinical care regarding access to an important monoclonal antibody, ramucirumab. Materials and Methods: Data for 13,340 cancer patients with Purchased or Medicaid insurance from the All of Us Database were collected for this study. The Chi-square test of proportions was employed to determine the significance of patient cohort characteristics and ramucirumab usage between Purchased and Medicaid insurance groups. The independent t-test was utilized to assess the influences of other determinants on insurance types. Results: Cancer patients who are African American, with lower socioeconomic status, or with lower educational attainment are more likely to be insured by Medicaid. Analysis of survey questions demonstrated the relationship between income and education level with insurance type as Medicaid cancer patients were less likely to receive primary care and specialist physician access and more likely to request lower cost medications. In addition, those with Medicaid insurance were identified to have poorer access to expensive therapeutics like ramucirumab compared to those with Purchased insurance.  Conclusions: The inequities of the US healthcare system are observed for cancer patient care; access to physicians and therapeutics are highly varied and dependent on insurance types. Socioeconomic status determines insurance type, which unfortunately generates a significant impact on cancer treatment and disease outcome.

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

Magnesium (Mg) is a vital element, which involves in various key cellular processes in plants. Mg transporter (MGT) genes play an important role in magnesium distribution and ionic balance maintenance. Here, MGT family members were identified and characterized in three species of the plant family Malvaceae, including Theobroma cacao, Corchorus capsularis, and Gossypium hirsutum to improve our understanding of their structure, regulatory systems, functions, and possible interactions. We identified 18, 41, and 16 putative non-redundant MGT genes from the genome of T. cacao, G. hirsutum, and C. capsularis, respectively, which were clustered into five groups within maximum likelihood tree. Several segmental/tandem duplication events were determined between MGTs genes. It seems that MGTs were slowly evolving and have been evolved under a purifying selection. Analysis of gene promoter regions showed that MGTs have a high potential to respond to biotic/abiotic stresses as well as hormones. The expression patterns of MGT genes revealed their possible T. cacaorole in response to P. megakarya fungi in T. cacao, whereas MGT genes showed differential expression in various tissues and respond to several abiotic stresses, including cold, salt, drought, and heat stress in G. hirsutum. Besides, the co-expressions network of MGTs indicated that genes involved in auxin responsive, lipid metabolism, cell wall organization, and photoprotection can interact with MGTs.

The aim of this study was to investigate the knowledge, attitudes, and behaviors of family physicians regarding testicular cancer and testicular self-examination. This study was conducted with 307 physicians, including family physician specialists, family physician residents, contracted family physician specialist assistants (SAHU), and general practitioners, who agreed to participate in the study. All participants were administered a 33-item questionnaire consisting of sociodemographic questions and questions about testicular cancer and testicular self-examination, developed through literature review. Data analysis was performed using SPSS 22.0 software. 307 family physician specialists, family physician residents, SAHU residents and general practitioners participated in the study. 10.4% of the participants were working as family medicine specialists, 67.4% as family physician assistants, 13.7% as SAHU residents and 8.5% as general practitioners. The mean time spent in the profession was found to be 5.93±5.89. 65.8% of the participants thought that they had partially sufficient knowledge about testicular cancers. 57.7% of the participants stated that they did not know how testicular self-examination was performed. 49.7% of male participants stated that they had never done testicular self-exam before. While 95.8% of the participants thought that regular testicular self-examination was beneficial, 71.0% stated that they did not recommend testicular self-examination to their male patients. 53.4% of the participants thought that testicular self-examination was important; It was determined that 79.2% of them thought it was as important as breast self-examination. The rate of stating that all of the risk factors presented for testicular cancer are risks was found to be statistically significantly higher in specialist family physicians than in general practitioners and resident family physicians. The study revealed that family physicians lacked sufficient knowledge about testicular cancer and testicular self-examination, leading them not to recommend self-testicular examination to patients due to inadequate knowledge. In light of these findings, although self-testicular examination may not be recommended as a screening method, increasing awareness and knowledge among both family physicians and the public is crucial.

In order to enhance understanding of RNA-binding proteins in rice, a comprehensive investigation was conducted on the RRM1 gene family of rice, encompassing genome-wide identification and exploration of its role in rice blast resistance. Physical and chemical properties of the OsRRM1 gene family in rice was analyzed, including conserved domain, motif, location information, gene structure, phylogenetic tree, collinearity analysis, cis-acting elements, GO, and KEGG. Furthermore, the expression patterns of the OsRRM1 gene were examined at different time intervals following rice blast treatment. Furthermore, the alterations in expression patterns of selected OsRRM1 genes were assessed using quantitative real-time PCR(qRT-PCR). A total of 212 members of the OsRRM1 gene family were identified, which were dispersed across 12 chromosomes. Many of these genes exhibit multiple exons and introns, all of which encompass the conserved RRM1 domain and share analogous motifs. This observation suggests a high degree of conservation within the encoded sequence domain of these genes. Phylogenetic analysis revealed the existence of five subfamilies within the OsRRM1 gene family. Furthermore, the investigation of the promoter region identified homeopathic elements that are involved in nucleic acid binding and interaction with multiple transcription factors. By employing GO and KEGG analysis, four RRM1 genes were tentatively identified as crucial contributors to plant immunity, while the RRM1 gene family was also found to have a significant involvement in the complex of alternative splicing. Additionally, gene expression analysis indicated that the majority of OsRRM1 genes exhibited constitutive expression. The results of the qRT-PCR analysis revealed distinct temporal changes in the expression pattern of the OsRRM1 gene following rice blast treatment. These findings contribute to the existing knowledge of the OsRRM1 gene family, establish a foundation for further investigation into the role of the OsRRM1 gene in response to rice blast infection, and hold theoretical significance for future studies on the functionality of the OsRRM1 gene.

Abstract Chaga´s disease caused by Trypanosoma cruzi infections is included in the group of neglected diseases, and efforts to develop new therapeutic or immunoprevention approaches have not been successful. After the publication of the T. cruzi genome, the number of molecular and biochemical studies on this parasite have increased considerably, many of which are focused on families of variant-surface-proteins, especially the trans-sialidases, mucins and mucin-associated proteins. The disperse gene protein 1 family (DGF-1) is one of the most abundant families in the T. cruzi genome, however, the large gene size, high copy numbers, and low antibody titers detected in infected humans make it an unattractive study target. Here, we argue that the DGF-1 gene family although not being the most obvious participant of the host-parasite immunological gamble, where T. cruzi appears to have the upper hand, it may play an important role in more basic host-parasite interactions that deserve further examination.

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants is a challenge to public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4,213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 from California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage, or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

Epilepsy is a common neurological condition, typically diagnosed using Electroencephalogram (EEG). Large scale EEG datasets have recently been made publicly available, allowing the use of advanced Machine Learning (ML) algorithms to analyze EEG patterns associated with epilepsy. While most existing studies focus on identifying seizures in the EEG, few have tried to identify preictal EEG segments. Identifying preictal EEG segments are not only useful in developing early warning systems but also helps inform the course of treatment for the patient. In this study, we propose to represent EEG segments as images, instead of time-series data, and identify preictal EEG segments using a preexisting ML algorithm (YOLOv8) designed for image processing. Multiplexed images (containing the original EEG signal represented on a 2D grid, kurtosis, and spectral entropy) achieve the best accuracy of 95.75% on the dataset while images just containing the EEG signal result in an accuracy of 91.25%. Using only spectrograms, generated from the original EEG signal, results in an accuracy of 90.15%.

Hepatocellular carcinoma (HCC) is one of the most frequent cancers in humans, characterised by high resistance to conventional chemotherapy, late diagnosis, and high mortality rate. It is necessary to elucidate the molecular mechanisms involved in hepatocarcinogenesis to improve diagnosis and treatment outcomes. The Runt-related (RUNX) family of transcription factors (RUNX1, RUNX2, and RUNX3) participates in cardinal biological processes and play paramount roles in the pathogenesis of numerous human malignancies. Their role is often controversial as they can act as oncogenes or tumour suppressors, dependent on cellular context. Evidence shows that deregulated RUNX genes may be involved in hepatocarcinogenesis from the earliest to the latest stages. In this review, we summarise the topical evidence on the roles of RUNX gene family members in HCC. We discuss their possible application as non-invasive molecular markers for early diagnosis, prognosis, and development of novel treatment strategies in HCC patients.

The subtilase family is the second largest family of serine proteases. Some fungi including Trichoderma species can capture and kill nematodes by secreting hydrolytic enzymes or toxins, among which serine proteases are important enzymes that allow fungi to infect nematodes. Subtilase can degrade nematode and insect body walls. In this study, subtilase family genes were identified from the Trichoderma harzianum genome database, and bioinformatics analysis of the characteristics and evolutionary status of these genes, along with structural and functional analyses of their proteins, was performed. Gene structure analysis revealed that all the 41 subtilase genes contained introns, while some did not have upstream or downstream regions. Chromosome localisation showed that subtilase family members were unevenly distributed in 22 Trichoderma chromosomes, and 3 clusters were present, indicating that they may be hot spots of subtilase genes. Conserved motif analyses showed these proteins contained a commonly conserved motif, and motifs belonging to the same subfamily remained highly similar. The upstream region of the subtilase genes were enriched with different type and numbers of cis-elements, indicating that subtilase genes are likely to play a role in the response to diverse stresses. Transcription of 31 genes was increased after 5 days of infection with nematodes, whereas that of 10 genes decreased. In these subtilase genes, ThSBT4, ThSBT5, ThSBT12, ThSBT27, ThSBT34, ThSBT35, ThSBT38, and ThSBT40 showed significantly upregulated expression with a log2 fold change value of more than 4, and ThSBT35 showed the highest peak. These results laid a theoretical foundation for further research on the function of the subtilase genes and the mechanism of the resistance response.

Introduction: Despite its high prevalence and impact on health, metabolic dysfunction-associated steatotic liver disease (MASLD) is inadequately addressed in European primary care (PC), with a large proportion of cases going undiagnosed or diagnosed too late. A multi-country European re-search consortium led a project to design and evaluate a patient-centered, integrated model for MASLD screening, diagnosis and linkage to specialty care for European PC settings. Aim: Based on the lessons from this project, the latest research evidence and existing guidelines for the management of MASLD, we sought to develop a set of practice recommendations for screening, referral and management of MASLD in PC. Methods: The Rand/UCLA modified Delphi panel method, with two rounds, was used to reach consensus on practice recommendations. The international panel consisted of experts from six countries, representing family medicine, gastroenterology, hepatology, cardiology and public health. Initially, fifteen statements were drafted based on a synthesis of evidence from the literature and earlier findings from our consortium. Prior to the consensus meeting, the statements were rated by the experts in a first round. Then, in a hybrid meeting, the experts discussed findings of round one, adjusted the statements and reassessed the updated recommendations in a second round. Results: In round one, there was already a high level of consensus on 10 out of 15 statements. After round 2, there were fourteen statements with a high agreement (>90%). One statement was not endorsed. The approved recommendations addressed the following practice areas: risk screening and diagnosis, management of MASLD – Lifestyle interventions, pharmacological treatment of MASLD/MASH, pharmacological treatment for co-morbidity, integrated care, surgical management and other referrals to specialists. Conclusion: The final set of 14 recommendations focuses on increasing comprehensive care for MASLD in PC. The recommendations provide practical evidence-based guidance tailored to PC practitioners. We expect that these recommendations will contribute to the ongoing discussion on systematic approaches to tackle MASLD and support European PC providers by integrating the latest evidence into practice.

Several specialized terpenoids that are used as phytoalexins are produced in the plant of tobacco. They play a key role in plant defense against pests and pathogens. Here, we performed genome-wide identification, classification, and expression profiling of the terpene synthase (TPS) genes in the tobacco genome. A total of 186 TPS genes were identified, which is significantly higher than that in wild Nicotiana, Capsicum and Solanum species. Phylogenetic analysis of these TPS genes in tobacco and Solanaceous relatives as well as Arabidopsis showed that a few tobacco-exclusive TPS clades occurred recently through gene duplication events. These clades are likely to be responsible for a range of compounds that separate N. tabacum cultivars from its wild relatives. Transcriptome sequencing of two cultivars of N. tabacum at several developmental stages revealed that some TPS genes from the TPS-a and TPS-b lineages are constitutively expressed and a few duplicated TPS genes are only expressed post anthesis at the time of harvest. Additionally, some TPS genes underwent alternative splicing, further diversifying the gene products of the TPS genes. Our findings provide an important candidate genes for further understanding of the diversity and evolution as well as functionality of TPS genes in the plant of tobacco.

Limited understanding exists regarding the intricate dynamics between the levels of social inhi-bition exhibited by both wives and husbands concerning their perceived family support and de-pressive symptoms, particularly within couples who are parents of children diagnosed with au-tism spectrum disorder (ASD). This study used the actor-partner, interdependence mediation model to analyze data collected from 397 pairs of Chinese parents with children diagnosed with ASD. The findings of the study revealed significant indirect actor effects, indicating that the levels of social inhibition exhibited by both wives and husbands were associated with their own de-pressive symptoms through their respective perceptions of family support. In general, the study did not find significant partner effects, except for some indirect effect (IE) of wives on their hus-bands' depressive symptoms through the wives' perceived social support. This observation sug-gests that cultural norms and role expectations within the family context may influence these dy-namics. These results underscore the potential importance of interventions aimed at addressing social inhibition and enhancing perceived family support to alleviate depressive symptoms in this population. Additionally, interventions targeting fathers should emphasize the importance of their involvement in parenting and collaboration with their partners in caring for children with ASD. Such collaborative efforts may contribute to improved outcomes for both parents and chil-dren within families affected by ASD.

Passion fruit is a valued tropical fruit crop that faces environment-related growth strains. TCP genes are important for both growth modulation and stress prevention in plants. Herein, we systematically analyzed the TCP gene family in passion fruit, recognizing 30 members. Genes exhibiting closer phylogenetic relationships exhibited similar protein and gene structures. Gene members of the TCP family showed developmental stage or tissue-specific expression profiles during the passion fruit life cycle. Transcriptome data also demonstrated that many PeTCPs showed induced expression in response to hormonal treatments and cold, heat, and salt stress. Based on transcriptomics data, eight candidate genes were chosen for preferential gene expression confirmation under cold stress conditions. Additionally, four TCP genes exhibited in silico binding with cold stress-related miRNA319s. This study will aid in the establishment of novel germplasm, as well as the further investigation of the roles of PeTCPs and their cold stress resistance characteristics.

LSU (RESPONSE TO LOW SULFUR) proteins belong to a plant-specific gene family initially characterized by their strong induction in response to sulfate (S) deficiency. However, little is known about the LSU gene repertoire and evolution of this family in land plants. In this work, a total of 270 LSU family members were identified using 134 land plant species with whole genome sequence available. Phylogenetic analysis revealed that LSU genes belong to a Spermatophyta-specific gene family, and their homologs are distributed in three major groups, two for dicotyledons and one group for monocotyledons. Moreover, we analyzed the expression of LSU genes in one representative species of each phylogenetic group (wheat, tomato and Arabidopsis) and found a conserved response to S-deficiency, suggesting that these genes might play a key role in S stress responses. Accordingly, Arabidopsis lsu2 knockout mutant plants showed increased levels of internal sulfate content and lower levels of expression of different key genes involved in S deficiency and metabolism like SDI2 and APR3. In summary, our results indicate that LSU genes are evolutionarily conserved in angiosperms and that specific members of this family might play an important role regulation of S transport and assimilation.

Transcription factors (TFs) in the homeodomain-leucine zipper (HD-ZIP) family serve as essential regulators of plant development and control responses to environmental stimuli. To date, however, the HD-ZIP gene family in Prunus nana remains to be fully characterized. Accordingly, a genome-wide analysis of P. nana HD-ZIP family genes was performed using the most recent genomic data available, leading to the classification of 30 HD-ZIP TFs. These genes were annotated and subjected to systematic analyses of phylogenetic relationships, protein physicochemical properties, sequence-based structural characteristics, chromosomal distributions, and associated cis-acting regulatory elements. High levels of diversity were observed with respect to the gene structures for these PnaHD-Zip genes and the cis-regulatory elements found in the promoter regions upstream of these genes, suggesting that they play diverse roles in a range of biological contexts. These 30 PnaHD-Zip genes were further classified into four subgroups based on the results of phylogenetic, gene structure, and conserved motif analyses. Subsequent qPCR analyses indicated that PnaHD-Zip1 and PnaHD-Zip7 expression levels tended to increase was continuously inhibited in response to cold stress, suggesting that proteins in this HD-ZIP gene family may exhibit distinct responses to low-temperature stress exposure. Overall, these results offer a robust foundation for future studies seeking to explore the functional roles that HD-ZIP TFs play as regulators of cold stress tolerance in P. nana, in addition to offering more general insight regarding the regulatory functions and characteristics of these different HD-ZIP genes in P. nana.

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

A screening questionnaire for autism symptoms is not yet available in Poland, and there are no recommendations regarding screening for developmental disorders in Polish primary health care. The aim of the study was to assess the opinions of parents and physicians on the legitimacy and ne-cessity of screening for autism spectrum disorders, potential barriers to the implementation of the screening program, and the evaluation and presenting the process of the online ASD screen-ing, which was part of the validation program of the Polish version of one of the screening tools. The study involved 418 parents whose children were screened online and 95 primary care physi-cians who expressed their opinions in prepared surveys. The results indicate that both parents and doctors perceive the need to screen children for ASD in general population without a clear preference as to the screening method (online or in-person). Online screening may prove to be at least a partial method of solving numerous indicated systemic difficulties - including: time con-straints, lack of experienced specialists in the field of developmental disorders or related to the organizational difficulties of health care.

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silencing a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1-4) peptides. The peptide:siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide:siRNA complexes showed serum stability at N/P ≥40. The synthesized conjugates, with a diameter of &lt;100 nm, formed nano complexes with siRNA and exhibited stable range of zeta potential values (13-18 mV at N/P 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of successful cellular internalization of siRNA. Peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.

(1) Background: Brassinosteroids (BRs) are an important hormone that participates in almost all stages of plant growth and development, and sterol dehydrogenase is a key enzyme that is involved in the biosynthesis of BRs. However, the steroid dehydrogenase gene family in Populus yunnanensis Dode (P. yunnanensis) has not been studied; (2) Methods: The PyDET2 gene family was identified and bioinformatics analyzed. Three genes were screened based on the RNA-seq of stem tip, the PyDET2e was further investigated by RT-qPCR (real-time quantitative polymerase chain reaction) and subcellular localization; (3) Results: We identified 14 DET2 family genes in P. yunnanensis that were classified into 4 groups according to sequence similarity and phylogenetic relationship, and 10 conserved protein motifs had been identified. The gene structure, chromosome distribution, collinearity, and codon preference of all PyDET2 genes identified in the genome of P. yunnanensis were analyzed. The codon of this family is biased to the end of A/U, and natural selection has a great influence on it. The expression level of PyDET2e in September was higher than in July, and it was significantly expressed in stems, stem tips, and leaves. The PyDET2e protein was localized in chloroplasts; (4) Conclusions: The PyDET2e is involved in the development of P. yunnanensis in the rapid growth stage. The systematic analysis provided a basis for the genome-wide identification of genes related to brassinolide biosynthesis processes in P. yunnanensis, and laid a foundation for the study on the mechanism of rapid growth of P. yunnanensis.

Trehalose is a non-reducing disaccharide and participates in physiological activities such as or-gan formation, energy metabolism, and stress resistance of insects. In the present study, phylo-genetic analysis divided 21 Bmtret1 orthologs into three clades. These genes are equally distrib-uted on the nine chromosomes. Cis-elements in the promoter regions of Bmtret1s indicated the possible function of Bmtret1s in response to hormones and environmental stimulus. The qPCR analysis showed the significantly different expression levels of Bmtret1s in different tissues and organs, indicating possible functional divergence. In addition, most Bmtret1s showed disturbed expression levels in response to BmNPV stresses. Our results provide a foundation for further functional dissection of Tret1s in Bombyx mori and implicate them as potential regulators for an-tiviral responses.

Being forced to live in an area following a catastrophic landslide may adversely impact people's mental well-being. Unprivileged communities such as Adivasis, Dalits, plantation workers, and people with low incomes in Kerala's hilly districts are forced to live in landslide-affected areas despite their fear. This paper examines the fears and concerns of landslide survivors from the marginalized sections of society from a broader framework of the political economy of mental health. This approach aligns with the assertion made by the World Health Organisation that individual factors do not solely determine mental health but are intricately linked to broader social, political, and economic circumstances. Data were collected through in-depth interviews with fatal landslide survivors and key informants [ ]. The study employed thematic data analysis from in-depth interviews of various fatal landslide survivors since 2018. The three major themes unveiled in the analysis are: 1. post-disaster fears, 2. The factors that triggered fear and concern and 3. Socio-economic marginality and mental health. The study asserts that individuals who are poor and unprivileged are highly susceptible to mental health issues associated with landslides.

This study investigates the effect of perceived discrimination on the mental health of Afghan refugees, and secondly, tests the distress moderating effects of pre-migration traumatic experiences and post-resettlement adjustment factors. In a cross-sectional design, 259 Afghans completed surveys assessing perceived discrimination and a number of other factors using scales developed through inductive techniques. Multivariate analyses consisted of a series of hierarchical regressions testing the effect of perceived discrimination on distress, followed by a sequential analysis of moderator variables. Perceived discrimination was significantly associated with higher distress, and this relationship was stronger among those with a strong intra-ethnic identity, high civic engagement, and high pre-resettlement traumatic experiences. Discrimination is a significant source of stress for Afghan refugees, which may exacerbate stresses associated with other post-migration stressors. Future research is needed to tailor interventions that can help mitigate the stress associated with discrimination among this highly vulnerable group.

A joint analysis of solar wind, geomagnetic field, and earthquake catalog data showed that before the catastrophic M7.8 and M7.5 Kahramanmaras earthquake sequence on February 6, 2023, the closed strong magnetic storm occurred on November 7, 2022, SYM/H=-117 nT. Storm started at 08:04 UT. At this time, the high latitudinal part of Turkey's longitudinal region of future epicenters was located under the polar cusp, where the solar wind plasma would directly access the Earth's environment. The time delay between storm onset and earthquake occurrence was ~91 days. We analyzed all seven strong (M7+) earthquakes from 1967 to 2020 to verify the initial findings. A similar pattern has been revealed for all events. The time delay between magnetic storm onset and earthquake occurrence varies from some days to some months. To continue these investigations, a retrospective analysis of seismic and other geophysical parameters just after preceded geomagnetic storms in the epicenter areas is desirable.

Osteoarthritis and chronic pancreatitis comorbidity are insufficiently studied, and the reciprocal impact of these conditions remains poorly understood. This study aimed to investigate potential predictors for the development of osteoarthritis and chronic pancreatitis comorbidity, as well as complications associated with this comorbidity. A cohort of 150 patients was categorized into three groups: a control group (n=30), patients with osteoarthritis (n=68), and patients with comorbid osteoarthritis and chronic pancreatitis (n=52). Potential predictors for comorbidity development and associated complications were explored. The study revealed that concurrent osteoarthritis and chronic pancreatitis exacerbate each other's progression and contribute to malnutrition. Body Mass Index (BMI) emerged as a potential predictor for chronic pancreatitis development in osteoarthritis patients. In osteoarthritis patients, fecal elastase-1 levels were identified as potential predictors for exocrine pancreatic insufficiency. Factors such as WOMAC total score, fecal elastase-1, C-reactive protein (CRP), ferritin, retinol, tocopherol, 25-hydroxy vitamin D3, and BMI were found to influence comorbidity development between osteoarthritis and chronic pancreatitis. Additionally, Gastrointestinal Symptom Rating Scale-Diarrhea Syndrome (GSRS-DS), Gastrointestinal Symptom Rating Scale-Constipation syndrome (GSRS-CS), Qualitative Assessment of the Symptoms and Impact of Pancreatic Exocrine Insufficiency domain A (PEI-Q-A), retinol, tocopherol, and iron were identified as potential predictors for exocrine pancreatic insufficiency in osteoarthritis patients. In conclusion, the comorbidity of osteoarthritis and chronic pancreatitis exacerbates disease progression and complications, necessitating further investigation.

Emphasis on primary health care (PHC) is the most efficient and economical approach to achieving universal health coverage. The aim of the study is to examine PHC publications from 2011 to 2023 in the Asian Pacific region (APR) using the Web of Science (WoS) database. Academic papers in the WoS PHC subject category published in the APR from 2011 to 2023 were retrieved and analyzed. A total of 4,283 papers were published in the WoS PHC category from APR onwards. The annual number of published papers and their citations increased from 2011 to 2023. Australia led PHC publications in APR with 3,049 publications (71.19% of APR regional output). New Zealand had the highest number of citations per paper (13.76) and the highest mean impact factor (3.23±1.80). Publications in the WoS PHC category also covered a wide range of topics, including Medicine General Internal (64.77%), Health Care Sciences Services (21.88%), Health Policy Services and Public Environmental Occupational Health (21.36%), demonstrating the breadth of PHC research. Australia dominates the output of PHC publications in the APR. Australian Family Physician and Australian Journal of Primary Health are the leading journals publishing PHC papers in the APR.

Background: Both hypertension and carotid atherosclerosis are independent risk factors for cardiovascular disease. Understanding their combined impact could enhance risk assessment and management strategies. Hypothesis: We hypothesized that the synergistic effects of hypertension and carotid plaques would increase the risk of both cardiovascular events and all-cause mortality. Methods: A follow-up study was conducted at the Preventive Cardiology department of Vilnius University Hospital Santaros klinikos between 2012 and 2021. The study recruited participants aged 40-60 who did not have overt CVD and were part of the Lithuanian High Cardiovascular Risk primary preventive program. The study collected demographic and clinical data, including an ultrasound assessment of carotid plaque. The participants were monitored for 4-10 years for CVD events and all-cause mortality. Results: Among 6,138 participants, 954 (16%) experienced cardiovascular disease (CVD) events. The presence of carotid plaque on both sides was significantly associated with CVD events, myocardial infarction, and all-cause mortality. However, the combination of hypertension and carotid plaque did not significantly increase the risk for CVD events, stroke, or all-cause mortality. Conclusion: The combination of hypertension and carotid plaque did not significantly increase the risk of CVD events or all-cause mortality. CV events depend on the spread of the atherosclerosis process in the carotid vessels.

HIV early detection (CD4 counts ≥350 cells/μL) is correlated with higher life expectancy among people living with HIV (PLHIV). Several factors including physical, cultural, structural, and financial barriers have contributed to HIV late detection. This is the first-of-its-kind study on the regional differences in early detection of HIV within Tajikistan and any country in the Central Asia region. Utilizing Tajikistan Ministry of Health's national HIV data (N=10,700) spanning 2010 to 2023, we developed median regression models with median CD4 cell count as the outcome and as predictors: time (years), region, age, gender, and area (urban/rural status). Individuals younger than 19 years old are more likely to be detected early for HIV, whereas those older than 39 years are more prone to late detection. Given their active engagement in age-related and sexual activities, those older than 39 years face a higher risk of HIV transmission to others if diagnosed late. Therefore, they require further attention and targeted interventions. Females are detected earlier compared to their male counterparts, regardless of region of residence. Rural populations are detected earlier in most years compared to their urban counterparts. The COVID-19 pandemic accelerated HIV early detection in 2021 but most regions have returned to near pre-pandemic levels of detection in 2022 and 2023. These fluctuations in early detection may signify a shift in attention and resource allocation, potentially affecting efforts to address access gaps during the initial year of the COVID-19 pandemic. There are significant health inequities among different demographic and geographic groups which warrant further attention.

Coccidioidomycosis (Valley Fever) is a disease caused by inhalation of Coccidioides spp. This neglected tropical disease of the Americas has substantial public health impact despite its geographic restriction to desert areas of the southwestern U.S., Mexico, Central and South America. The incidence of this infection in California and Arizona has been increasing over the past fifteen years. The burden of disease in outside the U.S. remains poorly understood. Several large cities are within the endemic region in the U.S. Coccidioidomycosis accounts for 25,000 hospital admissions per year in California. While most cases of coccidioidomycosis resolve spontaneously, up to 40% are severe enough to require anti-fungal treatment, and a significant number disseminate beyond the lungs. Disseminated infection, especially involving the meninges, is fatal without appropriate treatment. Infection with Coccidioides spp. is protective against a second infection, so vaccination seems biologically plausible. This review of efforts to develop a vaccine against coccidioidomycosis focuses on vaccine approaches and the difficulties in identifying protein antigen/adjuvant combinations that protect in experimental mouse models. Although the quest for a vaccine has not yet resulted in a clinically useful product, scientific efforts of vaccine development pave the way for future success.

Recent studies have emphasized the influence of resettlement factors on the mental health of refugees resettling in developed countries. However, little research has addressed gender differences in the nature and influence of resettlement stressors and sources of resilience. We address this gap in knowledge by investigating how gender moderates and mediates the influence of several sources of distress and resilience among 259 Afghan refugees residing in northern California. Gender moderated the effects of four factors on levels of distress. Intimate and extended family ties have little correlation with men’s distress levels, but are strongly associated with lower distress for women. English ability is positively associated with lower distress for women, but not men. In terms of gender ideology, traditionally oriented women and egalitarian men have lower levels of distress. And experiencing greater dissonant acculturation increases distress for men, but not women. The influence of gender interaction terms is substantial and patterns may reflect difficulty adapting to a different gender order. Future studies of similar populations should investigate gender differences in sources of distress and resilience, and efforts to assist new arrivals might inform them of changes in gender roles they may experience, and facilitate opportunities to renegotiate gender roles.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

Sulfate transporters (SULTRs) are responsible for the uptake of the sulfate (SO42−) ions in the rhizosphere by the roots and their distribution in plant organs. In this study, SULTR family members in the genome of the two oilseed crops, Camelina sativa, and Brassica napus, were identified and characterized based on their sequence structure, duplication events, phylogenetic relationships, phosphorylation sites, and expression levels. Herein, 36 and 45 putative SULTR genes were recognized from the genome of C. sativa, and B. napus, respectively. SULTR proteins were predicted as basophilic proteins with low hydrophilicity in both studied species. According to phylogenetic relationships, we divided SULTRs into five groups, in which SULTRs 3 showed highest variation. Besides, several duplication events were observed between SULTRs. The first duplication event was predicted approximately five million years ago between three SULTRs 3.1 in C. sativa. Two subunits were indicated in the 3D structure of SULTRs that the active binding sites differed between C. sativa and B. napus. According to available RNA-seq data, SULTRs showed diverse expression in tissues and response to stimuli. SULTRs 3 showed an expression in all tissues. SULTRs 3.1 were more upregulated in response to abiotic stresses in C. sativa, while SULTRs 3.3, and SULTRs 2.1 showed an upregulation in B. napus. Furthermore, SULTRs 3 and SULTRs 4.1 showed an upregulation in response to biotic stresses in B. napus. Based on the distribution of cis-regulatory elements in the promoter region, we speculated that SULTRs might be controlled by phytohormones such as ABA, and MeJA. Therefore, it seems that SULTR genes in C. sativa have been more influenced by evolutionary processes and have acquired more diversity.

ESG (Environmental, Social, and Governance) responsibility fulfillment increasingly affects enterprise valuation. Although researchers debate about the precise effects, the prevailing view suggests a linear relationship between ESG performance and enterprise value. This study introduces a novel ESG responsibility performance metric through the Regulated Intermediary Model to delve into this relationship within the Chinese context. Our findings reveal an inverted U-shaped relationship between ESG performance and enterprise value, with financing constraints having a significant moderating effect. These findings remain robust after employing instrumental variables to mitigate potential endogeneity. Heterogeneity analysis demonstrates that this inverted U-shaped relationship is particularly pronounced in non-polluting and non-state-owned enterprises. Moreover, a comparison between equity and debt financing mechanisms underscores that improved ESG performance is associated with lower cost of equity financing, thereby enhancing enterprise value. Financial institutions are encouraged to leverage innovative financial instruments to diversify enterprise financing channels and alleviate financing constraints of enterprises that fulfill their ESG responsibilities.

Cucumber (Cucumis sativus L.) is a vital economic vegetable crop, and TRM (TONNEAU1 Recruiting Motif) gene plays a key role in cucumber organ growth. However, the pan-genomic characteristics of the TRM gene family and their expression patterns under different stresses have not been reported in cucumber. In this study, we identified 29 CsTRMs from the pan-genomes of 13 cucumber accessions, with CsTRM29 existing only in PI183967. Most CsTRM proteins exhibited differences in sequence length, except five CsTRMs having consistent protein sequence lengths among the 13 accessions. All CsTRM proteins showed amino acid variations. Analysis of CsTRM gene expression patterns revealed that six CsTRM genes strongly changed in short-fruited lines compared with long-fruited lines. And four CsTRM genes strongly responded to salt and heat stress, while CsTRM14 showed responses to salt stress, powdery mildew, gray mold and downy mildew. Some CsTRM genes were induced or suppressed at different treatment timepoint, suggesting that cucumber TRM genes may play different roles in responses to different stresses, with expression patterns varying with stress changes. Remarkably, the expression of CsTRM21 showed considerable change between long and short fruit and in responses to abiotic stresses (salt stress, heat stress) as well as biotic stresses (powdery mildew, gray mold), suggesting a dual role of CsTRM21 in both fruit shape determination and stress resistance. Collectively, this study provided a base for further functional identification of CsTRM genes in cucumber plant growth and stress resistance.

LSUs (RESPONSE TO LOW SULFUR) are plant-specific proteins of unknown function that were initially identified during transcriptomic studies of the sulfur deficiency response in Arabidopsis. Recent functional studies have shown that LSUs are important hubs of protein interaction networks with potential roles in plant stress responses. In particular, LSU proteins have been reported to interact with members of the brassinosteroid, jasmonate signaling, and ethylene biosynthetic pathways, suggesting that LSUs may be involved in response to plant stress through modulation of phytohormones. Furthermore, in silico analysis of the promoter regions of LSU genes in Arabidopsis has revealed the presence of cis-regulatory elements that are potentially responsive to phytohormones such as ABA, auxin, and jasmonic acid, suggesting crosstalk between LSU proteins and phytohormones. In this review, we summarize current knowledge about the LSU gene family in plants and its potential role in phytohormone responses.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

According to their nutritional value, their ability to adapt to the various environmental conditions, and their versatility, cereals are among the most cultivated plants in the world. However, the ongoing climate changes subject crops to important environmental stress that for some varieties leads to high production losses. Therefore, selection of species and varieties more versatile and adaptable to different environmental conditions can be important. However, the characteristics of some cereals are not completely known, this is a priority before to improve their cultivation. The aim of this study is to characterize select species of potential suitable for local environmental conditions, nutritional value.

Although Eulerian approaches are standard in computational acoustics, they are less effective for certain classes of problems like bubble acoustics and combustion noise. A different approach for solving acoustic problems is to compute with individual particles following particle motion. In this paper, a Lagrangian approach to model sound propagation in moving fluid is presented and implemented numerically, using three meshfree methods to solve the Lagrangian acoustic perturbation equations (LAPE) in the time domain. The LAPE split the fluid dynamic equations into a set of hydrodynamic equations for the motion of fluid particles and perturbation equations for the acoustic quantities corresponding to each fluid particle. Then, three meshfree methods, the smoothed particle hydrodynamics (SPH) method, the corrective smoothed particle (CSP) method, and the generalized finite difference (GFD) method, are introduced to solve the LAPE and the linearized LAPE (LLAPE). The SPH and CSP methods are widely used meshfree methods, while the GFD method based on the Taylor series expansion can be easily extended to higher orders. Applications to modeling sound propagation in steady or unsteady fluids in motion are outlined, treating a number of different cases in one and two space dimensions. A comparison of the LAPE and the LLAPE using the three meshfree methods is also presented. The Lagrangian approach shows good agreement with exact solutions. The comparison indicates that the CSP and GFD method exhibit convergence in cases with different background flow. The GFD method is more accurate, while the CSP method can handle higher Courant numbers.

Magnesium transporters (MGTs) play a prominent role in the absorption, transport and storage of magnesium in plant cells. In the present study, MGT gene family members were identified and characterized in two species of cucurbitaceae, including C. sativus and C. lanatus. 20, 19, and 20 MGT genes were recognized in C. lanatus, C. sativus, and C. melo, respectively. According to physicochemical properties, the members of each sub-class of MGTs in the species of cucurbitaceae showed the close relationship. Proteins from NIPA were identified as hydrophilic proteins with high stability. Based on phylogenetic analysis, MGT family members were classified into three groups, and NIPAs showed more diversity. Besides, duplication events were not identified between the MGT members in C. lanatus, and C. sativus. According to pocket analysis, residues such as L, V, S, I, and A were frequently observed in the binding sites of MGT proteins in both species. The prediction of post-translation modifications revealed that MSR2 proteins have high phosphorylation potential than other sub-classes in both studied plants. The expression profile of MGTs showed that MGTs are more expressed in root tissues. In addition, MGTs showed differential expression in response to abiotic/biotic stresses as well as hormone application and NIPAs were more induced in response to stimuli in watermelon. The results of this study, as the primary work of MGT gene family, can be used in programs related to cucurbitaceae breeding.

The CDPK family genes play crucial roles in signal transduction pathways during plant develop-ment and stress response. In this study, we comprehensively analyzed the CDPK family genes in mustard (Brassica juncea L.), resulting in the identification of 101 genes (BjuCDPK1–101) located on chromosomes AA_Chr01 to BB_Chr08. RNA-seq analysis showed that most BjuCDPK genes were predominantly expressed in the root and flower bud, suggesting their organ-specific expression patterns. Furthermore, the expression levels of most BjuCDPK genes were significantly altered by cold stress. The promoter regions of BjuCDPK genes had abundant cis-acting elements related to hormone and stress. The interaction network analysis predicted that BjuCDPK proteins respond to abiotic stress probably via interaction with ABF1, ABF4, and/or DI19. Our findings provide valu-able information for further investigation of the cold stress adaption of mustard via the CDPK signaling pathway.

During the response of plants to adverse stresses, aquaporin (AQP) plays a prominent role in membrane water transport based on received upstream signals. In addition, they have various physical parts for dealing with environmental stresses. Due to the importance of the AQP gene family, studies have been conducted investigating the function and regulatory system of these genes. However, many of their molecular aspects are still unknown. This study aims to carry out a genomic-wide investigation of the AQP gene family in durum wheat using bioinformatics tools and to investigate the expression patterns of some members in response to salt stress. Our results showed that there are 80 TtAQP genes in durum wheat, which are classified into four main groups based on phylogenetic analysis. Many duplications were observed between the members of the TtAQP gene family, and high diversity in response to post-translational modifications was observed between TtAQP family members. The expression pattern of TtAQP genes disclosed that these genes are primarily upregulated in response to salt stress. Besides, qPCR data revealed that TtAQPs are more induced in delayed responses to salinity stress. Overall, our findings illustrate that TtAQP members are diverse in terms of their structure, regulatory systems and expression levels.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of final steps in virion maturation. Earlier studies indicated that three pp150nt (N terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B) and extend towards small capsid proteins atop nearby major capsid proteins forming a net-like layer of tegument densities that enmesh and stabilize HCMV capsids. Based on this atomic detail, we designed several peptides targeting pp150nt. Our data show significant reduction in virus growth upon treatment with one of these peptides (pep-CR2) with an IC50 of 1.33 μM. Based on 3D modeling, pep-CR2 specifically interferes with the pp150-capsid binding interface. Cells pre-treated with pep-CR2 and infected with HCMV sequester pp150 in the nucleus indicating a mechanistic disruption of pp150 loading onto capsids and subsequent nuclear egress. To enhance the in-vivo inhibitory potential and bioavailability of pep-CR2, we conjugated it with a carrier molecule (elastin like polypeptide (ELP)). The ELP-pep-CR2 conjugate was expressed in E.coli and purified. Upon treatment with ELP-pep-CR2, HCMV showed significant titer reductions with no significant impact on cell viability. These results indicate that CR2 of pp150 is amenable to targeting by a peptide inhibitor and can be developed into an effective antiviral.

The objective was to investigate associations of serum vitamin D concentration with depressive symptoms and assess the impact vitamin D concentration has on the occurrence of depressive symptoms in 20–44-year-old pregnant mothers, postpartum mothers, women (non-pregnant/postpartum women), and men, including a separate subgroup analysis of postpartum breastfeeding and non-breastfeeding mothers. The study populations were selected from 2007-2018 NHANES public data. Subjective interview data and objective laboratory data, including depressive symptoms, serum vitamin D concentration, nutrient intake, and demographic information were utilized. Two diet patterns were created using principal component analysis and a Bayesian multinomial model was fit to predict depression outcomes for each subpopulation. The estimates for the log vitamin D slope parameter were negative for all cohorts; as vitamin D increased, the probability of having no depression increased, while the probability of depression decreased. The pregnant cohort had the steepest vitamin D slope, followed by postpartum, then other women and men. Higher vitamin D concentration had more impact on decreasing depression risk in pregnant and postpartum mothers compared to other women and men. Among postpartum mothers, higher vitamin D concentration had a greater influence on decreasing breastfeeding mothers' depression risk than non-breastfeeding mothers.

MicroRNAs, short non-protein coding RNAs, are overexpressed in GCTs. Circulating levels of germ cell tumor (GCT)- associated miRNAs, such as miR-371a-3p, can be utilized as efficient and cost-effective alternatives in diagnosing and managing patients presenting with GCTs. This quality of miRNAs has demonstrated favorable performance characteristics as a reliable blood-based biomarker with high diagnostic accuracy compared to current serum tumor markers (STMs) including α-fetoprotein (AFP), beta human chorionic gonadotropin (β-hCG), and lactate dehydrogenase (LDH). The conventional STMs exhibit limited specificity and sensitivity. Potential clinical implications of miRNAs include impact on de-escalating or intensifying treatment, detecting recurrence at earlier stages, and lessening the necessity of cross-sectional imaging or invasive tissue biopsy for non-teratomatous GCTs. Here we also highlight the outstanding issues that must be addressed prior to clinical implementation. Standards for measuring circulating miRNAs and determining ideal cutoff values are essential for integration into current clinical guidelines.

Beta thalassemia is an inherited blood disorder that results in inefficient erythropoiesis due to genetic mutation that leads to reduction or absence of the hemoglobin beta-globulin protein. Approximately 8.5% of UAE residents suffer from β-thalassemia, a significant health and financial problem. The treatment options available for β-Thalassemia major are limited and associated with a wide range of complications. β-thalassemia gene therapy is emerging as a potential novel treatment option that eliminates the complications caused by the current long-term treatment modalities and the associated economic burden. This paper reviews the scientific literature related to emerging gene-therapy for β-Thalassemia by analyzing all the articles published from January 2010 to December 2023 in the English language on Databases like PubMed, Scopus, ProQuest, and CINAHL. The use of gene therapy has demonstrated promising outcomes for a permanent cure of β-Thalassemia. ZYNTEGLO (Betibeglogene autotemcel) is the only cell-based gene therapy which was approved by the FDA on 19th August, 2018. To conclude, Gene therapy is an innovative solution. It demonstrates a promising future, but does come with its own set-backs and is something that must be tackled in-order to revolutionize it in the medical world. FDA approved ZYNTEGLO is a potentially one-time curative treatment for β-Thalassemia. Although cutting-edge, its use is limited because of the high cost; a price of $2.8million per patient.

During the 3rd millennium cal BC, the Indus communities exploited great quantities of chert from the Rohri Hills mines in Upper Sindh for making different types of artefacts. This paper discusses the way chert was transported to the Indus Civilization centres and the problems related to the type, quantity and quality of raw material and artefacts that were transported, when, why, and where. This paper raises the question of land and water transport. Both these methods were probably used according to the landscape location of the Indus sites. Another problem regards the landscape characteristics of the Indus Valley during the Bronze Age before the climate changes which took place around the end of the 3rd millennium cal BC, and the disappearance of the Hakra River, which was an important watercourse during the Indus phase. What do we know of the way the Indus communities exploited, transported, and circulated knappable chert? Why the Indus settlements excavated around the Rohri Hills, the largest chert mines of the Indian Subcontinent, have yielded little evidence of chert artefacts and nodules? What do we know of this important problem which is strictly related with the everyday life of the Indus communities and their economy? Why this problem has been systematically neglected by most archaeologists despite its importance?

Nitrogen (N) is an important mineral nutrient for plant growth, as well as a limiting factor for crop yield, and how to improve the utilization efficiency of N fertilizer by plants is currently a research hotspot. This article uses bioinformatics methods to identify and analyze members of the glutamine synthetase (GS) and glutamate synthase (GOGAT) gene families in pecan. A total of 6 GS genes and 4 GOGAT genes were identified, and their physicochemical properties, gene structures, and homologous evolutionary relationships were analyzed. Analysis of tissue-specific expression of GS and GOGAT genes based on transcriptome data from pecan. The enzyme activities of GS and GOGAT and the gene expression were quantitatively analyzed under different N form ratios in pecan. According to the results, the promoter cis-acting elements of GS and GOGAT genes can be roughly divided into three types: light-responsive elements, hormone-responsive elements, and stress-responsive elements. The results of homologous evolution showed that there was no tandem duplication event for the two gene families, and GS and GOGAT have undergone purification during the evolutionary process. CiGS2s and CiFd-GOGATs were expressed mainly in leaves, and CiNADH-GOGATs were expressed mainly in fruits. The qPCR analysis results showed that T4 treatment significantly increased the expression levels of CiGS and CiGOGAT genes in the leaves. The enzyme activities of GS and GOGAT in pecan were significantly increased under T3, T4, and T5 treatments. In summary, a higher proportion of ammonium nitrogen (NH4+) in the nutrient solution was profit to pecan NH4+ assimilation. This study determined the appropriate nitrogen ratio for pecan, promoting a theoretical basis for reducing environmental pollution caused by nitrogen fertilizer and improving the nitrogen utilization efficiency of pecan. In summary, both CiGSs and CiGOGATs exhibit tissue specificity, and an ammonium-nitrate mixture with a higher proportion of NH4+ is more favorable for NH4+ assimilation in pecan. This study provides a reference basis for further understanding the functions of CiGSs and CiGOGATs in pecan, and offers a theoretical foundation for improving N use efficiency in pecan.

Introduction The prevalence of adolescent electronic cigarette (e-cigarette) use has increased in most countries. This study determines the relation between the frequency of e-cigarette use and the frequency and intensity of cigarette smoking. Furthermore, it evaluates the association between the reasons for e-cigarette use and the frequency of its use. Materials and Methods Participants were 68,043 middle and high school students aged 13–18 years from the 2015 Korean Youth Risk Behavior Web-Based Survey. Of the 68,043 participants, we analyzed 6,655 adolescents with an experience of e-cigarette use. Results The prevalence of ever using and current (past 30 days) use of e-cigarettes was 10.1% and 3.9%, respectively. Of the ever e-cigarette users, approximately 40% used e-cigarettes for ≥1/month and 8.1% used e-cigarettes daily. Daily e-cigarettes users were 10 times greater among daily cigarette smokers than among cigarette users for <1/month (18.1% vs. 1.8%) and 16 times more prevalent among those smoking ≥20 cigarettes/day than among those smoking <1 cigarette/month (38.9% vs. 2.4%). The most common reason for e-cigarette use was curiosity (22.9%), followed by less harmful than conventional cigarettes (18.9%), smoking cessation (13.1%), and indoor use (10.7%). Curiosity was the most common reason among less frequent e-cigarette users; however, smoking cessation and indoor use were the most common reasons among more frequent users. Conclusions Results showed a positive relation between frequency or intensity of conventional cigarette smoking and frequency of e-cigarette use among Korean adolescents, and frequency of e-cigarette use differed according to the reason for the use of e-cigarettes.

We report diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), a rare, hereditary neurodegenerative disease of childhood, in a four and a half year old girl, the first child of non-consanguineous parents with no family history. Despite extensive efforts by the parents, her clinical condition remained undiagnosed and without management, until recently. Our published “Bottom-up Approach”, based on comprehensive and multidisciplinary clinical, pathological, radiographical and genetic evaluations, played key role in diagnosis of the disease. Detailed analyses involving Next Generation Sequencing confirmed a missense variation NC_00011.10:g.6616374C>T (NP_000382.3:p.Arg339Gln; rs765380155) in exon 8 of TPP1 gene. In silico analyses predicted it to be highly pathogenic. Further family screening (including her both unaffected parents and asymptomatic, one year old younger sister) of the identified variation through Sanger Sequencing, revealed a perfect autosomal recessive segregation in the family. This study is the first case report on classic CLN2 from Jammu and Kashmir-India. This study is also indicating the effectiveness of our “Bottom-up Approach” in understanding rare disorders in low resource regions and the importance of timely diagnosis. Like in the proband, had diagnosis been established a bit early, the family might have benefitted at least with reference to their second child through counselling programmes.

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

Lettuce (Lactuca sativa) is a leafy vegetable that provides a valuable source of phytonutrients for a healthy human diet. Assessment of plant growth and composition is vital for determining crop yield and overall quality, however, classical laboratory analyses are slow and costly. Therefore, new, less expensive, more rapid, and non-destructive approaches are being developed, including those based on (hyper)spectral reflectance. Additionally, it is also important to determine how plant phenotypes respond to fertilizer treatments and whether these differences in response can be detected from analyses of hyperspectral image data. In the current study, we demonstrate the suitability of hyperspectral imaging in combination with machine learning models to estimate the content of chlorophyll (SPAD), anthocyanins (ACI), glucose, fructose, sucrose, vitamin C, β-carotene, N, P, K, dry matter content, and plant fresh weight. The implemented five classification and regression machine learning models showed high accuracy in classifying the lettuces by the applied fertilizers treatments and estimating nutrient concentrations. To reduce the input (predictor data, i.e., hyperspectral data) dimension, 13 principal components were found and applied in models. The implemented artificial neural network models of the machine learning algorithm demonstrated high accuracy (r = 0.85 ... 0.99) in estimating fresh leaf weight, and contents of chlorophyll, anthocyanins, N, P, K, and β-carotene. The four applied classification models of machine learning demonstrated 100% accuracy in classifying the studied baby leaf lettuces by phenotype when certain fertilizer treatments were applied.

Plant Cysteine Oxidase (PCO) is a plant O2-sensing enzyme of catalyzing oxidation of cysteine to Cys-sulfinic acid at the N-termini of target proteins. To better understand the Brassica napus PCO gene family, PCO genes in B. napus and related species were analyzed. In this study, 20, 7 and 8 PCO genes were identified in Brassica napus, Brassica rapa and Brassica oleracea, respectively. According to phylogenetic analysis, the PCOs were divided into five groups: PCO1, PCO2, PCO3, PCO4 and PCO5. Gene organization and motif distribution analysis suggested that PCO gene family was relatively conserved during evolution. Expression analysis showed that PCO genes were expressed in different tissues at different developmental stages. Interestingly, most of the Bna/Br/BoPCO5 members were expressed in leaves, roots, flowers, buds and siliques, suggesting an important role in both vegetative and reproductive development. Expression of BnaPCO was induced by various abiotic stress, especially waterlogging stress, which was consistent with the result of cis-element analysis. In this study, the PCO gene family of Brassicaceae was analyzed for the first time, which contributes to a comprehensive understanding of the origin and evolution of PCO genes in Brassicaceae and the function of BnaPCO in regulating plant responses to abiotic stresses.

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

Many risk-modifying factors affect cancer incidence and mortality rates. We present an ecological study of incidence and/or mortality rates for cancers during 2007–2016 of 17 anatomical sites with respect to solar ultraviolet-B (UVB) doses and obesity prevalence. Solar UVB reduces cancer risk by producing vitamin D, which has many mechanisms to reduce risk of cancer incidence, progression, and metastasis. Obesity increases cancer risk through several mechanisms, including increased systemic inflammation. Data were averaged for 12 geographical regions. Solar UVB doses were significantly inversely correlated with mortality rates for five cancers for males and four for females. Obesity prevalence was directly correlated with mortality rates for three cancers for males and seven for females. The population attributable fraction of cancer mortality rates ascribed to low solar UVB dose was 0.03 for both males and females, whereas that for obesity prevalence was 0.05 for males and 0.08 for females. Thus, cancer mortality rates in France could be reduced through vitamin D supplementation and reducing the prevalence of obesity. Doing so also could reduce risk of other adverse health outcomes.

bZIP transcription factors, basic leucine zipper, play significant roles in plants’ growth and development processes, as well as in response to biological and abiotic stress. Hypericum perforatum is one of the world's top three best-selling herbal medicines, mainly used to treat depression. However, there is no systematic identification or functional analysis of the bZIP gene family in H. perforatum. In this study, 79 HpbZIP genes were identified. Based on phylogenetic analysis, the HpbZIP gene family was divided into ten groups, designated A-I, and S. The physicochemical properties, gene structures, protein conserved motifs, and Gene Ontology enrichments of all HpbZIPs were systematically analyzed. The expression patterns of all genes in different tissues of H. perforatum (root, stem, leaf, and flower) were analyzed by qRT-PCR, revealing the different expression patterns of HpbZIP under abiotic stresses. HpbZIP69 protein is localized in the nucleus. According to the results of the yeast one-hybrid (Y1H) assays, HpbZIP69 can bind to the HpASMT2 (N-Acetylserotonin O-methyltransferase) gene promoter ( G-box cis-element ) to activate its activity. Overexpressing HpbZIP69 transgenic Arabidopsis lines enhanced tolerance to drought. The content of MDA and H2O2 content was significantly decreased, and the activity of superoxide dismutase (SOD) was considerably increased under the drought stress. These results may aid in additional functional studies of HpbZIP transcription factors and cultivating drought-resistant medicinal plants.

Indocyanine Green (ICG) has significantly advanced minimally invasive surgery. It is widely recognized for its ability to visualize blood vessel patency in real-time across various surgical specialties. While its primary use in colorectal surgery is to evaluate anastomoses for leaks, nu-merous other applications have been documented in the literature. In this review, we aim to explore both established and emerging applications of ICG fluorescence in colorectal surgery, with the goal of improving patient outcomes. This includes preoperative tumor marking and the detection of metastatic disease. Some applications, such as lymphatic mapping, require further research to determine their impact on clinical practices. Conversely, oth-ers, like the intraoperative localizations of ureters, necessitate additional procedures and are not yet widely accepted by the surgical community. However, the development of alternative com-pounds could offer better solutions. Future research should focus on areas like quantitative ICG and protocol standardization in prospective multicenter studies.

(1) Background: There is insufficient empirical evidence on the correlates of health care utilization of irregular migrants currently living in Turkey. The aim of this study was to identify individual level determinants associated with health service and medication use. (2) Methods: 155 Afghans completed surveys assessing service utilization including encounters with primary care physicians and outpatient specialists in addition to the use of prescription and nonprescription medicines. Multivariate logistic regression analyses were employed to examine associations between service use and a range of predisposing, enabling, and perceived need factors. (3) Results: Health services utilization was lowest for outpatient specialists (20%) and highest for nonprescription medications (37%). Female gender and higher income predicted encounters with primary care physicians. Income, and other enabling factors such as family presence in Turkey predicted encounters with outpatient specialists. Perceived illness-related need factors had little to no influence on use of services; however, asylum difficulties increased the likelihood for encounters with primary care physicians, outpatient services, and the use of prescription medications. 4) Conclusion: This study suggests that health services use among Afghan migrants in Turkey is low considering the extent of their perceived illness-related needs, which may be further exacerbated by the precarious conditions in which they live.

In a safety-critical system typically not all provided services have the same criticality, which we call mixed-criticality systems. Criticality arithmetic, also called SIL arithmetic, is an approach to lower the development effort of a service by providing redundancy with tasks that are developed for a lower criticality level. In this paper we present ATMP-CA, which is a derivation of the multi-core scheduler ATMP. ATMP-CA is able to take into account the knowledge about the use of criticality arithmetic. ATMP-CA has a modified core allocation and procedure for utility optimisation, considering the context of the replicated tasks. We conducted experiments that show that ATMP-CA is able to provide the services using criticality arithmetic, while the reference schedulers were not.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

Artificial intelligence (AI) is experiencing advances and integration in all medical specializations, and this creates excitement but also concerns. This narrative review aims at a critical assessment of the state of the art of AI in the field of endometriosis and adenomyosis. By enabling automation, AI may speed up some routine tasks, decreasing gynecologists’ risk of burnout, as well as enabling them to spend more time interacting with their patients, increasing their efficiency and patients’ perception of being taken care of. Surgery may also benefit from AI, especially through its integration with robotic surgery systems. This may improve the detection of anatomical structures and enhance surgical outcomes by combining intra-operative findings with pre-operative imaging. Not only, AI promises to improve the quality of care by facilitating clinical research and through the introduction of decision support tools that can enhance diagnostic assessment and predict treatment effectiveness and side effects, as well as reproductive prognosis and cancer risk. However, concerns exist regarding the fact that good quality data used in tool development and compliance with data sharing guidelines are crucial. Also, professionals are worried AI may render certain specialists obsolete. This said, AI is more likely to become a well-liked team member rather than a usurper.

P-band radar remote sensing applied during the Airborne Microwave Observatory of Subcanopy and Subsurface (AirMOSS) mission has shown great potential for estimation of root zone soil moisture. When retrieving the soil moisture profile (SMP) from P-band radar, a mathematical function describing the vertical moisture distribution is required. Because only a limited number of observations are available, the number of free parameters of the mathematical model must not exceed the number of observed data. For example, a second order polynomial that contains 3 free parameters was presumed based on in-situ SMP data. The polynomial is currently parameterized based on 3 backscatter observations provided by AirMOSS (i.e. one frequency at three polarizations of HH, VV and HV). In this paper, a more realistic, physically-based SMP model containing 3 free parameters is derived based on a solution to Richards’ equation for unsaturated flow in soils. Evaluation of the new SMP model based on both numerical simulations and measured data revealed that it exhibits greater flexibility for fitting measured and simulated SMPs than the currently applied polynomial. It is also demonstrated that the new SMP model can be reduced to a second order polynomial at the expense of fitting accuracy.

The largest gene families in plants were found to be Glutathione transferase (GSTs), which played significant roles in regulating plant growth, development, and stress response. Within the GSTs gene family, members were found to play a crucial role in the low-temperature response process of plants. A comprehensive study identified a total of 70 BraGSTs genes. Cluster analysis results demonstrated that the BraGSTs in Brassica rapa(B.rapa) could be categorized into eight sub-families and were unevenly distributed across ten chromosomes. The 39 BraGSTs genes were found to be organized into 15 tandem gene clusters, with the promoters containing multiple cis-elements associated with low-temperature response. Cold stress was observed to stimulate the expression of 15 genes, with the BraGSTF2 gene exhibiting the highest level of expression, sug-gesting its significant involvement in winter B.rapa's response to low-temperature stress. Sub-cellular localization analysis of the BraGSTF2 protein indicated its potential expression in both the cell membrane and nucleus. The analysis of stress resistance in BraGSTF2 transgenic Arabidopsis thaliana lines emon-strated that the over-expression of this gene resulted in significantly elevated levels of SOD, POD activity, and SP content compared to the wild type following exposure to low temperatures. These levels reached their peak after 24 hours of treatment. Conversely, the MDA content was lower in the transgenic plants compared to the wild type. Additionally, the survival rate of BraGSTF2 transgenic Arabidopsis thaliana was higher than that of the wild type, suggesting that the BraG-STF2 gene may play a crucial role in enhancing the cold stress tolerance of winter B. rapa. This study lay a foundation for further study on the role of BraGSTs gene in the molecular regulation of cold resistance in winter B.rapa.

The basic helix-loop-helix (bHLH) transcription factor family is the second-largest transcription factor in plants. Members of this family are involved in the process of growth and development, secondary metabolic biosynthesis, signal transduction, and plant resistance. Loropetalum chinense var. rubrum is a critical woody plant with higher ornamental and economic values, which used as ornamental architecture and traditional Chinese herbal medicine plant. However, the bHLH transcription factor in the L. chinense var. rubrum (Loropetalum chinense var. Rubrum) have yet to be systematically demonstrated, and their role in anthocyanin biosynthesis remains secret. Here, we identified 165 potential LcbHLHs genes by two methods, and they were unequally distributed on chromosomes 1 to 12 of the L. chinense genome. Based on a phylogenetic comparison with proteins from Arabidopsis, these bHLH proteins were categorized into 21 subfamilies. Most LcbHLHs in a given subfamily had similar gene structures and conserved motifs. The gene ontology annotation and cis-elements predicted that the LcbHLHs had many molecular functions and were involved in plant growth processes, including flavonoid and anthocyanin biosynthetic processes, etc. Transcriptomic analysis revealed different expression patterns among different tissues and cultivars in L. chinense. Many LcbHLHs were expressed in leaves, and only a few genes were highly expressed in flowers. Six LcbHLH genes differentially expressed between species and periods in color variation, which may play a key role in anthocyanin synthesis. These further functional predictions of LcbHLHs were established by quantitative real-time PCR analysis and protein-protein interaction network. This study identified the six potential bHLH genes related to anthocyanin in L. chinense and created a solid framework for future research on the function and evolution of bHLHs.

Total ankle replacement (TAR) implants are an effective option to restore the range of motion of the ankle joint for arthritic patients. An effective tool for analyzing these implants’ mechanical performance and longevity in-silico is finite element analysis (FEA). ABAQUS FEA was used to statically analyze the von Mises stress and contact pressure on the articulating surface of the bearing component in two newly installed fixed-bearing total ankle replacement implants (the Wright Medical INBONE II and the Exactech Vantage). This ultra-high molecular weight polyethylene (UHMWPE) bearing commonly fails and is the cause for surgeon revisions. Six different FEA models for various gait percentages during stance (10%-60%) were created. They varied in magnitude of the compressive load and the ankle dorsiflexion/plantarflexion angle. The results indicated that the von Mises stress and contact pressure distributions increased as compressive load increased, and the largest magnitudes occurred at high dorsiflexion angles (15-30°). High magnitudes occurred in regions where the thickness of the bearing was the least. Additionally, high contact pressures were examined in areas near the talar component's edge or at the bearing's edges. To the author’s knowledge, this is the first study available to the research community that analyzes the Vantage implant with FEA. This study lays an essential foundation for future researchers in presenting a thorough literature review of TAR and methods for a simple FEA model setup. This study provides valuable information that can be beneficial to medical company designers and orthopedic surgeons in understanding the stress response and contact pressure of TAR implants during use.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

The rates of obesity and obesity-related diseases continue to increase worldwide, classifying obesity as a global epidemic. Endogenous opioids have been implicated in influencing feeding behavior; however, the role of each opioid peptide is still only partially characterized. Therefore, we assessed the role of the proopiomelanocortin (POMC)-derived peptide beta-endorphin (β-END) in long-term high-fat diet (HFD) feeding and glucose homeostasis and assessed if sex-related differences exist in these processes. Male and female mice lacking the ability to produce β-END and their respective controls were subjected to a 12-week HFD consumption to determine the role of the opioid peptide in food intake and glucose homeostasis. Body weight and food intake were measured weekly for twelve weeks. At weeks 6 and 12, plasma glucose levels were measured using an oral glucose tolerance test. Here, we report that male β-END deficient mice gained more weight and consumed more calories than their wildtype controls; however, this difference was not observed in the female mice. Regardless of genotype, female mice consumed more calories per body weight when compared to male mice despite their smaller body weights. Moreover, our findings suggest differences in glucose homeostasis between the wildtype and knockout mice and that these were only observed at week six but not at week 12. Overall, our study suggests that endogenous β-END may play a role in controlling body weight, feeding behavior, and glucose homeostasis and that sex-related differences may exist in this regard.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Insecurity, corruption, and rising unemployment have resulted in a mass exodus of young adult Afghans seeking asylum in western nations. This has depleted Afghanistan of generations of young people which are critical to rebuild the country. This study aimed to examine the characteristics of young adult Afghans with no immediate intentions of seeking international asylum; that is, individuals who intend to stay in Afghanistan. In a cross-sectional study conducted in Kabul, we surveyed 232 young adults between 18 and 35 years of age. Surveys included measures assessing standard socio-demographic and -economic factors, as well as health and psychological factors. Univariate logistic regression analyses suggest that participants with an intent to stay in Afghanistan are more likely to be financially stable, possess higher health-related quality of life, lower psychological distress, and higher levels of hope and optimism, as well as higher resilience. When controlling for all other variables in the model, only hope, optimism, and higher resilience remained as significant correlates of intending to stay. Our findings suggest that young people who intend to stay in their country look forward to a better future, which provides strong evidence for the need to strengthen the social contract by fostering resilience, hope and optimism in war-affected communities, in order to prevent a generation of talented young people from seeking asylum in western nations.

Real time camouflaged object detection so far using CAMO or COD10K datset has been able to achieve mAP50 less than 64%. We present a fourier transfom and Milkyway filament extraction based method extracting shape and edges of camouflaged object, achieving 88%+ mAP50 while continuing to deliver real time detection using YOLOv8s based models. This allows for search and rescue of wilelife and humans in smoke, fog, natural disasters possible by combining low compute Yolov8s model on headup display for rescue workers such as firefighters, first reponders etc.

The heavy-metal-associated (HMA) proteins are a class of PB1-Type ATPases related to the intracellular transport and detoxification of metals. However, due to a lack of information regarding the HMA gene family in the Cucurbitaceae family, a comprehensive genome-wide analysis of the HMA family was performed in ten Cucurbitaceae species: Citrullus amarus, Citrullus colocynthis, Citrullus lanatus, Citrullus mucosospermus, Cucumis melo, Cucumis sativus, Cucurbita maxima, Cucurbita moschata, Cucurbita pepo, and Legenaria siceraria. We identified 103 Cucurbit HMA proteins with various members, ranging from 8 (Legenaria siceraria) to 14 (Cucurbita pepo) across species. The phylogenetic and structural analysis confirmed that the Cucurbitaceae HMA protein family could be further classified into two major clades: Zn/Co/Cd/Pb and Cu/Ag. GO annotation-based subcellular localization analysis predicted that all HMA gene family members were localized on membranes. Moreover, the analysis of conserved motifs and gene structure (intron/exon) revealed the functional divergence between clades. Interspecies microsynteny analysis demonstrated that maximum orthologous genes were found between species of the Citrullus genera. Finally, nine candidates HMA genes were selected, and their expression analysis was carried out via qRT-PCR in root, leaf, flower, and fruit tissues of C. pepo under arsenic stress. The expression pattern of the CpeHMA genes showed a distinct pattern of expression in root and shoot tissues, with a remarkable expression of CpeHMA6 and CpeHMA3 genes from the Cu/Ag clade. Overall, this study provides insights into the functional analysis of the HMA gene family in Cucurbitaceae species and lays down the basic knowledge to explore the role and mechanism of the HMA gene family to cope with arsenic stress conditions.

Phospholipases are among the important elements involved in lipid-dependent cell signaling that lead to the induction of downstream pathways. In the current study, phospholipases D (PLDs) gene family was characterized and compared in two important oilseeds crops, Brassica napus and Camelina sativa. The results revealed that PLD has 33 members in Camelina sativa (CsPLD) and 41 members in Brassica napus (BnPLD). All studied PLDs showed a negative GRAVY value, indicating that PLDs are probably hydrophilic proteins. Phylogenetic analysis separated PLDs into five subfamilies; gamma, delta, beta, alpha, and zeta. According to evolution analysis, a different evolution process was observed between CsPLD and BnPLD. In addition, the results disclosed that the most of the PLD genes have been segmentally duplicated under purifying selection. Cis-regulatory elements related to ABA and auxin responsiveness were more found in upstream region of CsPLDs, while elements linked with MeJA responsiveness were more dis-tributed in promoter region of BnPLDs. Analysis of the expression data showed that PLD alpha genes have a wide expression and are expressed in most tissues. Quantitative expression analysis (qPCR) of CsPLD genes under salt stress, 200 mM of NaCl, was done in different time series. The results revealed that the CsPLD genes are involved in the response to salinity stress and their expression levels enhance with the increase of salinity stress time. The outcomes of this research will be useful for future molecular work related to lipid signaling in oilseed plants.

Various kinds of primary metabolisms in plants are modulated through sulfate assimilation that the uptake of this inorganic compound can be regulated via the sulfate transporters, such as sulfotransfer-ases (SOTs), engaged in the sulfur metabolism. In the current study a genome-wide approach has been utilized for recognition and characterization of SOT family genes in the significant nutritional crop po-tato (Solanum tuberosum L.). As a result, 29 StSOT genes were identified in the potato genome, which were mapped onto the nine S. tuberosum chromosomes. The protein motifs structure demonstrated two highly conserved 5' PSB region and 3' PB motif that are essential for sulfotransferase and catalytic ac-tivities. The protein-protein interaction networks also significantly demonstrated an interesting collabo-ration between SOTs and the other genes, such as PRTase, APS-kinase, protein phosphatase and APRs, in sulfur compounds biosynthesis and regulation of the flavonoid and brassinosteroid metabolic pro-cesses, which clearly detected the importance of sulfotransferases for potato proper growth/development and stress dealing. Notably, the homology modeling of StSOT proteins and dock-ing analysis of their ligand-binding sites revealed the presence of some stress-responsive residues, such as proline, glycine, serine and lysine, in their active sites. The expression assay of StSOT genes via the potato RNA-seq data clearly suggested the engagements of these gene family members in plants growth and extension as well as responses to various hormones and biotic/abiotic stimulus circum-stances. Our predictions can be informative for the functional characterization of the SOT genes in po-tato and may the other nutritional crops.

Abstract: Transcription factors are crucial pre-transcriptional regulatory mechanisms that can modulate the expression of downstream genes by binding to their promoter regions. DOF (DNA binding with One Finger) proteins are a unique class of transcription factors with extensive roles in plant growth and development. Our previous research indicated a decrease in iron content in chlorotic bamboo leaves. However, to our knowledge, genes related to iron metabolism pathways in bamboo species have not yet been studied. Therefore, in the current study, we identified iron metabolism-related (IMR) genes in bamboo and determined the transcription factors that significantly influence them. Among these, DOFs were found to have widespread effects and potentially significant impacts on their expression. We identified specific DOF members in Dendrocalamus latiflorus with binding abilities through homology with Arabidopsis DOF proteins, and established connections between some of these members and IMR genes using RNA-seq data. Additionally, molecular docking confirmed the binding interactions between these DlDOFs and the DOF binding sites in the promoter regions of IMR genes. The co-expression relationship between the two gene sets was further validated using q-PCR experiments. This study paves the way for research into iron metabolism pathways in bamboo and lays the foundation for understanding the role of DOF transcription factors in D. latiflorus.

In this paper, the sol−gel method was used to synthesize powders of LaMnO3 (LMO), La0.85Ca0.15MnO3 (LCM), and La0.85Sr0.15MnO3 (LSM). We investigated the impact of substituting Ca and Sr at the A−site on the perovskite crystal structure and electrochemical capabilities of LMO. LCM retained its orthogonal structure in comparison to the parent LMO components, whereas LSM transitioned to a rhombic structure. At 0.5 A/g, the specific capacitance of LCM and LSM electrodes is 185.5 F/g and 248 F/g, respectively.The specific capacitance of LCM was more three times than that of the LMO electrode. Among the three samples (LMO, 22.25 m2 g−1; LSM, 31.56 m2 g−1), the LCM sample exhibited the highest specific surface area of 38.79 m2 g−1. The charge transfer resistances of the LMO, LCM, and LSM are 0.48 Ω, 0.36 Ω, and 0.38 Ω, correspondingly. The LCM electrode exhibits the greatest capacitance performance due to its more refined morphology, increased concentration of oxygen vacancy, and more complete utilization of the perovskite bulk structure. The above results demonstrate that Ca or Sr substitution of A−site compounds has great potential for supercapacitor applications.

Sirtuins (SIRTs) are a family of evolutionarily conserved enzymes, and the aim of this study was to disclose/re-annotate uncertain paralogs in gilthead sea bream, expanding from seven to ten the repertoire of Sirts in this Perciform fish. Such gene expansion revealed up to three copies of sirt3 (sirt3.1a/sirt3.1b/sirt3.2) and two of sirt5 (sirt5a/sirt5b). Phylogenetic and synteny attempts disclosed the duplication of SIRT3/Sirt3 branch as a process shaped by the 2R whole genome duplication (WGD) at the early vertebrate evolution, with still vestiges in all living fish, and some Sarcopterygii. In gilthead sea bream and other Percomorphaceae, this duplication was accompanied by short segmental duplications of sirt3.1 (clustered to the mammalian SIRT3 ortholog), making a conserved tandem-duplicated synteny block (psmd13-sirt3.1a/b-drd4-cdhr5-ctsd). Conversely, the expansion of the Sirt5 branch was shaped by the 3R WGD as a specific event of the teleost fish lineage. Intriguingly, gene expression profiling across tissues and developmental stages highlighted a conserved high expression of sirt3.1 and sirt5a in skeletal muscle, while the duplicated sirt3.2 and sirt5b displayed an overall muscle suppression of transcriptional activity, and an enhanced expression on immune-relevant tissues and gills, respectively. Altogether offers new insights about the function, regulation, and timing of Sirt expansion.

Tomato (Solanum lycopersicum) is one of the most cultivated vegetables in the world due to its consumption in a large variety of raw, cooked, or processed foods. Tomato breeding and productivity highly depend on the use of hybrid seeds and their higher yield, environmental adaption, and disease tolerance. However, the emasculation procedure during hybridization raises tomato seed production costs and labor expenses. Using male sterility is an effective way to reduce the cost of hybrid seeds and ensure cultivar purity. Recent developments in CRISPR genome editing technology enabled tomato breeders to investigate the male sterility genes and to develop male-sterile tomato lines. In the current study, the tomato Acotinase (SlACO) gene family was investigated via in-silico tools and functionally characterized with CRISPR/Cas9-mediated gene disruption. Genome-wide blast and HMM search represented two SlACO genes located on different tomato chromosomes. Both genes were estimated to have a segmental duplication in the tomato genome due to their identical motif and domain structure. One of these genes, SlACO2, showed a high expression profile in all generative cells of tomato. Therefore, the SlACO2 gene was targeted with two different gRNA/Cas9 construct to identify their functional role in tomato. The gene was mutated in a total of 6 genome-edited tomato lines, 2 of which were homozygous. Surprisingly, pollen viability was found to be extremely low in mutant plants compared to their wild-type (WT) counterparts. Likewise, the number of seeds per fruit also sharply decreased more than fivefold in mutant lines (10-12 seed) compared to that in WT (67 seed). The pollen shape, anther structures, and flower colors/shapes were not significantly varied between the mutant and WT tomatoes. The mutated lines were also subjected to salt and mannitol-mediated drought stress to test the effect of SlACO2 on abiotic stress tolerance. The results of the study indicated that mutant tomatoes have higher tolerance with significantly lower MDA content under stress conditions. This is the first CRISPR-mediated characterization of ACO genes on pollen viability, seed formation, and abiotic stress tolerance in tomato.

The search of DNA polymorphisms useful for the genetic improvement of dairy farm animals lasts more than 40 years with relevant findings in cattle for milk traits, where the best combination of alleles for dairy processing have been found in casein genes and in the DGAT1. Nowadays, similar results are not reached yet in river buffaloes despite advanced genomic technologies and accurate phenotype records are available. The aim of the present study was to investigate and validate in a larger buffalo population the effect on six milk traits of four single nucleotide polymorphisms (SNP) in the CSN1S1, CSN3, SCD and LPL genes, previously reported to be associated with or affect dairy traits in smaller populations often belonging to one farm. A total of 800 buffaloes were genotyped. Daily milk yield (dMY, kg), protein yield (dPY, kg) and fat yields (dFY, kg), fat and protein contents (dFP, % and dPP, %), somatic cell count (SCC, 103cell/ml) and urea (mg/dl) were individually recorded in each month for the whole lactation from 2010 to 2021. A total of 15,742 individual milk test day records (2,496 lactations) were available on 680 buffalo cows with 3.6±1.7 parity (from 1 to 13) and 6.1±1.2 test day records per lactation on average. Three out four SNP in CSN1S1, CSN3 and LPL were associated with at least one of analyzed traits. In particular, the CSN1S1 (AJ005430:c.578C&gt;T) gave favorable associations with all yield traits (dMY, p=0.022; dPY, p=0.014 ; dFY, p=0.029) and SCS (p=0.032), whereas the CSN3 (HQ677596: c.536C&gt;T) positively associated with SCS (p=0.005) and milk urea (p=0.04). Favorable effect on dMY (p=0.028), dFP (p=0.027) and dPP (p=0.050) were observed for the LPL. Conversely, SCD did not show any association with milk traits. This is the first example of confirmation study carried out in the Mediterranean river buffalo for genes of economic interest in dairy field and it represents a very important indication for the preselection of young bulls destined to breeding programs in the view of a more sustainable dairy production.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persists throughout the world with over 65 million registered cases of survivors with post-COVID-19 sequelae, also known as LongCOVID-19 (LongC). LongC survivors exhibit various symptoms that span multiple organ systems, including the nervous system. To search for neurological biomarkers of LongC, we investigated the soluble proteins present in the plasma and the proteins associated with plasma neuronal-enriched extracellular vesicles (nEVs) in 33 LongC patients with neurological impairment (nLongC), 12 COVID-19 survivors without any LongC symptoms (Cov), and 28 pre-COVID-19 healthy controls (HC). COVID-19 positive participants were infected from 2020-2022, not hospitalized, and were vaccinated or unvaccinated before infection. IL-1b was significantly increased in both nLongC and Cov and IL-8 elevated in only nLongC. Both brain-derived neurotropic factor and cortisol were significantly elevated in nLongC and Cov compared to HC. nEVs from people with nLongC had significantly elevated protein markers of neuronal dysfunction, including amyloid beta 42, pTau181 and TDP-43. This study shows chronic peripheral inflammation with increased stress after COVID-19 infection. Additionally, differentially expressed nEV neurodegenerative proteins were identified in people recovering from COVID-19 regardless of persistent symptoms.