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Potassium ion channels play a fundamental role in regulating cell membrane repolarization, modulating the frequency and shape of action potentials, and maintaining the resting membrane potential. A growing number of studies have indicated that dysfunction in potassium channels associates with the pathogenesis and treatment of depression. However, the involvement of potassium channels in the onset and treatment of depression has not been thoroughly summarized. In this review, we performed a comprehensive analysis of the association between multiple potassium channels and their roles in depression, and compiles the SNP loci of potassium channels associated with depression, as well as antidepressant drugs that target these channels. We discussed the pivotal role of potassium channels in the treatment of depression, provide valuable insights into new therapeutic targets for antidepressant treatment and critical clues to future drug discovery. [ABSTRACT FROM AUTHOR]

Background: Although caffeine (CAF) supplementation has been shown to improve exercise performance, its dose-dependent effect on CAF metabolism has not been sufficiently investigated. The aim of this study was to evaluate the effects of 3, 6 and 9 mg of CAF/kgBM on changes of CAF and paraxanthine (PRX) in the serum and saliva at four time-points. Methods: In a randomized, double-blind, placebo-controlled crossover design, acute pre-exercise supplementation in 26 moderately-trained athletes, participating in high-intensity functional training (HIFT), was examined. The study protocol involved CAF/PRX biochemical analyses of serum and saliva with respect to CYP1A2 polymorphism and CYP1A2 enzyme activity. Results: Despite significant differences between the serum and saliva levels of CAF and PRX, there was no difference in the PRX/CAF ratio. The interaction effect of dose and time-points for PRX concentration was revealed. The main effects of dose were observed for CAF and the PRX/CAF ratio. The main effect of time-points was registered only for serum CAF. Conclusions: Dose- and time-dependent effect of CAF supplementation on CAF and PRX in the serum and saliva of athletes was confirmed, but there was no effect of the CAF dose on CYP1A2 enzyme activity, nor was there an interaction of CYP1A2 with enzyme inducibility. The CAF/PRX correlation indicated the possibility of interchangeable use of serum and/or saliva analyses in exercise studies. Clinical trial registration: This trial was registered prospectively at ClinicalTrials.gov (NCT03822663, registration date: 30/01/2019). [ABSTRACT FROM AUTHOR]

Background: Despite the growing number of studies investigating the connection between host genetics and the rumen microbiota, there remains a dearth of systematic research exploring the composition, function, and metabolic traits of highly heritable rumen microbiota influenced by host genetics. Furthermore, the impact of these highly heritable subsets on lactation performance in cows remains unknown. To address this gap, we collected and analyzed whole-genome resequencing data, rumen metagenomes, rumen metabolomes and short-chain fatty acids (SCFAs) content, and lactation performance phenotypes from a cohort of 304 dairy cows. Results: The results indicated that the proportions of highly heritable subsets (h2 ≥ 0.2) of the rumen microbial composition (55%), function (39% KEGG and 28% CAZy), and metabolites (18%) decreased sequentially. Moreover, the highly heritable microbes can increase energy-corrected milk (ECM) production by reducing the rumen acetate/propionate ratio, according to the structural equation model (SEM) analysis (CFI = 0.898). Furthermore, the highly heritable enzymes involved in the SCFA synthesis metabolic pathway can promote the synthesis of propionate and inhibit the acetate synthesis. Next, the same significant SNP variants were used to integrate information from genome-wide association studies (GWASs), microbiome-GWASs, metabolome-GWASs, and microbiome-wide association studies (mWASs). The identified single nucleotide polymorphisms (SNPs) of rs43470227 and rs43472732 on SLC30A9 (Zn2+ transport) (P < 0.05/nSNPs) can affect the abundance of rumen microbes such as Prevotella_sp., Prevotella_sp._E15-22, Prevotella_sp._E13-27, which have the oligosaccharide-degradation enzymes genes, including the GH10, GH13, GH43, GH95, and GH115 families. The identified SNPs of chr25:11,177 on 5s_rRNA (small ribosomal RNA) (P < 0.05/nSNPs) were linked to ECM, the abundance alteration of Pseudobutyrivibrio_sp. (a genus that was also showed to be linked to the ECM production via the mWASs analysis), GH24 (lysozyme), and 9,10,13-TriHOME (linoleic acid metabolism). Moreover, ECM, and the abundances of Pseudobutyrivibrio sp., GH24, and 9,10,13-TRIHOME were significantly greater in the GG genotype than in the AG genotype at chr25:11,177 (P < 0.05). By further the SEM analysis, GH24 was positively correlated with Pseudobutyrivibrio sp., which was positively correlated with 9,10,13-triHOME and subsequently positively correlated with ECM (CFI = 0.942). Conclusion: Our comprehensive study revealed the distinct heritability patterns of rumen microbial composition, function, and metabolism. Additionally, we shed light on the influence of host SNP variants on the rumen microbes with carbohydrate metabolism and their subsequent effects on lactation performance. Collectively, these findings offer compelling evidence for the host-microbe interactions, wherein cows actively modulate their rumen microbiota through SNP variants to regulate their own lactation performance. C1VA69ck9huqCRa2wNrTKW Video Abstract [ABSTRACT FROM AUTHOR]

Objective: Analyze the ultrasound findings, single nucleotide polymorphism array (SNP-array) results, and pregnancy outcomes of fetuses with 7q11.23 deletions and duplications in the second and third trimesters. Investigate the prenatal ultrasound characteristics and follow up information of these fetuses. Methods: Seven fetuses were diagnosed with 7q11.23 deletion and six with 7q11.23 duplication via SNP-array at the prenatal diagnosis center of a single Chinese tertiary medical center from January 2017 to May 2024. Maternal demographics, ultrasound findings, SNP-array results, pregnancy outcomes, and follow-up information were comprehensively reviewed and analyzed. Results: The copy number variations (CNVs) ranged from 1.43 Mb to 1.78 Mb in cases of 7q11.23 deletions and from 1.42 Mb to 1.68 Mb in cases of 7q11.23 duplications. These CNVs encompassed 29 OMIM-listed genes, including ELN, DNAJC30, GTF2IRD1, and GTF2I. Among the seven cases of 7q11.23 deletion syndrome, six exhibited ultrasound abnormalities. The main clinical phenotypes included three cases of intrauterine growth restriction and four cases of cardiovascular system abnormalities, specifically two cases with ventricular septal defects, one case with aortic narrowing, and one case with supravalvular pulmonary stenosis. One case was particularly notable, exhibiting complex multi-organ structural malformations. Out of six cases of 7q11.23 duplication syndrome, five exhibited ultrasound abnormalities. These included two cases of cardiovascular abnormalities: one case with a widened left ventricle and another case with a shortened fetal humerus length. One case revealed complex multi-organ structural malformations, including hydronephrosis, a microgallbladder, and a cleft lip and palate. All seven cases of 7q11.23 deletions and three cases of 7q11.23 duplications opted for termination of the pregnancy. The remaining three cases of 7q11.23 duplications chose to continue the pregnancy. One case underwent surgical treatment for a ventricular septal defect after birth, and the prognosis was favorable. Another case involved a full-term delivery, this child was followed up at the age of 4 and exhibited a phenotype of poor language expression ability. Conclusion: Our study broadened the clinical phenotype spectrum of fetuses with 7q11.23 deletions and duplications. Additionally, it conducted a preliminary evaluation of prenatal ultrasound findings and postnatal clinical phenotypes in follow-up cases. The clinical phenotype of fetuses with 7q11.23 deletion and duplication syndromes involves multiple systems and is relatively complex. Cardiovascular abnormalities and intrauterine growth restriction are the most common clinical manifestations observed in prenatal 7q11.23 deletion syndrome. Fetuses with 7q11.23 duplications exhibit a wide range of clinical phenotypes that lack specificity. [ABSTRACT FROM AUTHOR]

Background: Xinglong buffalo, as an indigenous breed in Hainan province of China, possesses characteristics such as high humidity tolerance, disease resistance and high reproductive capacity. Combined with whole genome sequencing technology, comprehensive investigation can be undertaken to elucidate the genomic characteristics, functions and genetic variation of Xinglong buffalo population. Results: Xinglong buffalo has the highest genetic diversity, lowest runs of homozygosity average length, and fasted decay of linkage disequilibrium in our study population. Phylogenetic tree results revealed that Xinglong buffalo was gathered together with Fuzhong buffalo firstly. The population genetic structure analysis indicates that at K = 3, the Xinglong buffalo for the first time showed a distinct ancestral origin from other water buffalo. Furthermore, compared to different populations, candidate genes displaying significantly distinct patterns of single nucleotide polymorphisms (SNPs) (e.g., RYR2, COX15, PCDH9, DTWD2, FCRL5) distribution have been identified in the Xinglong buffalo. Conclusions: Based on the whole genome sequencing data, this study identified a substantial number of SNPs and assessed the genetic diversity and selection signatures within the Xinglong buffalo population. These results contribute to understanding the genomic characteristics of Xinglong buffalo and their genetic evolutionary status. However, the practical significance of these signatures for genetic enhancement still requires confirmation through additional samples and further experimental validation. [ABSTRACT FROM AUTHOR]

Background: Embryonic genome activation (EGA) is a critical step in early embryonic development, as it marks the transition from relying on maternal factors to the initiation of transcription from embryo's own genome. The factors associated with EGA are not well understood and need further investigation. PRD-like (PRDL) homeodomain transcription factors (TFs) are considered to play crucial roles in this early event during development but these TFs have evolved differently, even within mammalian lineages. Different numbers of PRDL TFs have been predicted in bovine (Bos taurus); however, their divergent evolution requires species-specific confirmation and functional investigations. Results: In this study, we conducted molecular cloning of mRNAs for the PRDL TFs ARGFX, DUXA, LEUTX, NOBOX, TPRX1, TPRX2, and TPRX3 in bovine oocytes or in vitro fertilized (IVF) preimplantation embryos. Our results confirmed the expression of PRDL TF genes in early bovine development at the cDNA level and uncovered their structures. For each investigated PRDL TF gene, we isolated at least one homeodomain-encoding cDNA fragment, indicative of DNA binding and thus potential role in transcriptional regulation in developing bovine embryos. Additionally, our cDNA cloning approach allowed us to reveal breed-related differences in bovine, as evidenced by the identification of a high number of single nucleotide variants (SNVs) across the PRDL class homeobox genes. Subsequently, we observed the prediction of the 9aa transactivation domain (9aaTAD) motif in the putative protein sequence of TPRX3 leading us to conduct functional analysis of this gene. We demonstrated that the TPRX3 overexpression in bovine fibroblast induces not only protein-coding genes but also short noncoding RNAs involved in splicing and RNA editing. We supported this finding by identifying a shared set of genes between our and published bovine early embryo development datasets. Conclusions: Providing full-length cDNA evidence for previously predicted homeobox genes that belong to PRDL class improves the annotation of the bovine genome. Updating the annotation with seven developmentally-important genes will enhance the accuracy of RNAseq analysis with datasets derived from bovine preimplantation embryos. In addition, the absence of TPRX3 in humans highlights the species-specific and TF-specific regulation of biological processes during early embryo development. [ABSTRACT FROM AUTHOR]

Streptococcus suis serotypes 2 and 14 are the most common zoonotic strains, but previous identification methods made distinguish these two serotypes from other S. suis serotypes difficult. To effectively prevent and control them, there is an urgent need for a highly sensitive and specific method to identify these two serotypes. In this study, a fluorescent probe was designed for the single nucleotide polymorphism site at cpsK 483 of Streptococcus suis type 2 and type 14 compared with other serotypes, and an enzyme-activated probe quantitative PCR (EA-probe qPCR) method was established for the detection of Streptococcus suis type 2 and type 14 by combining with the specific hydrolysis characteristics of the RNase H2 enzyme. The results showed that the optimal probe concentration for this method was 0.5 µM and the optimal RNase H2 enzyme concentration was 25 mU.This method showed no reactivity with genomic DNA from Streptococcus suis strains 1/2, 5, 7, 9, 23, 28, 29, and 31, confirming its high specificity. And its sensitivity can reach 18.4 CFU. In addition, 19 clinical strains of Streptococcus suis type 2 or type 1/2 were tested. The results showed 100% agreement with the gene sequencing method. In conclusion, this method can meet the needs of accurate laboratory testing of Streptococcus suis serotypes 2 and 14 and has value for clinical prevention. [ABSTRACT FROM AUTHOR]

Background: A single nucleotide polymorphism (SNP) is a variation in the DNA sequence that results from the alteration of a single nucleotide in the genome. Atorvastatin is used to treat hypercholesterolemia. It belongs to a class of drugs called statins, which lower elevated levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). Research findings on the associations between the response to atorvastatin and genetic polymorphisms in CYP3A4 and CYP3A5 are inconclusive. The effects of CYP3A4*1B (rs2740574 C/T) and CYP3A5*3 (rs776746 T/C) on atorvastatin therapy have not been previously studied among Egyptians. Objective: This research aimed to investigate the effects of the genetic polymorphisms CYP3A4*1B and CYP3A5*3 on atorvastatin treatment in Egyptians. Methods: In this prospective cohort study, 100 subjects were genotyped for these SNPs. All participants were screened for serum lipid profiles, liver enzymes, total bilirubin (TB), and creatine kinase (CK) before and after 40 mg postatorvastatin therapy. Atorvastatin plasma levels were assessed posttreatment; atorvastatin pharmacokinetics were evaluated in five carriers of the CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes. Results: The allele frequencies of the CYP3A4*1B and CYP3A5*3 SNPs were 86% and 83%, respectively. The CYP3A4*1B (T/T) and CYP3A5*3 (C/C) genotypes significantly improved the serum triglyceride (TG) level (P < 0.05) and elevated the TB level (P < 0.001). Atorvastatin plasma levels were greater in CYP3A4*1B (T/T) (P < 0.05) and CYP3A5*3 (C/C) (P < 0.001) genotype carriers. Both SNPs significantly affected the pharmacokinetics of atorvastatin compared with those of Egyptian volunteers and various ethnic populations. Conclusions: The CYP3A4*1B and CYP3A5*3 variants were prevalent in the study participants and could impact the effectiveness and safety of atorvastatin therapy. The mutant genotype of the CYP3A4*1B SNP and the CYP3A5*3 SNP led to high atorvastatin levels. Both variants had a notable effect on the pharmacokinetics of atorvastatin among Egyptians compared with healthy Egyptians and volunteers from other ethnic populations. Overall, clinicians can learn more about the impact of both variants in response to atorvastatin. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a complex heterogenous disorder manifesting with various reproductive, endocrine, and metabolic derangements such as insulin resistance and hyperglycemia. The arginine vasopressin peptide (AVP), also called or antidiuretic hormone (ADH), modulates metabolic functions such as glucose hemostasis, insulin sensitivity, and lipid metabolism via binding to two central and peripheral receptors (AVPR1A and AVPR1B). In the present study, we aimed to detect whether the AVPR1A and AVPR1B genes confer risk for PCOS. Methods: In peninsular Italian families, we tested 7 variants in the AVPR1B gene and 2 variants in the AVPR1A gene via Pseudomarker for linkage and linkage joint to association (i.e.., linkage disequilibrium) with PCOS. Results: We identified two risk variants in each gene, significantly associated with the risk of PCOS. Conclusion: To the best of our knowledge, this is the first study to report risk variants in AVPR1A and AVPR1B genes in association with PCOS. However, replication in other ethnic groups as well as functional studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Background: PfAP2-EXP2 is located within chromosome 6 of Plasmodium falciparum recently identified to be undergoing an extensive selective sweep in West African isolates. The gene encoding this transcription factor, PfAP2-EXP2, is essential and thus likely subject to purifying selection that limits variants in the parasite population despite its genomic location. Methods: 72 Plasmodium falciparum field samples and 801 clinical sequences from the Pf6 MalariaGEN dataset of Ghanaian origin, were integrated and analysed. Results: A total of 14 single nucleotide variants of which 5 were missense variants, were identified after quality checks and filtering. Except for one, all identified variants were rare among the clinical samples obtained in this study (Minor allelic frequency < 0.01). Further results revealed a considerably low dN/dS value (0.208) suggesting the presence of purifying selection. Further, all the mutant amino acids were wildtype residues in AP2-EXP2 orthologous proteins—tentatively suggesting a genus-level conservation of amino acid residues. Computational analysis and predictions corroborated these findings. Conclusions: Despite the recent extensive selective sweep within chromosome 6 of West African isolates, PfAP2-EXP2 of Ghanaian origin exhibits low nucleotide diversity and very low dN/dS consistent with purifying selection acting to maintain the function of an essential gene. The conservation of AP2-EXP2 is an important factor that makes it a potential drug target. [ABSTRACT FROM AUTHOR]

Background: Lumpy Skin Disease (LSD) is endemic in sub-Saharan countries and is currently a global threat to the cattle industry. Information on the circulating Capripoxvirus lumpyskinpox, formerly known as Lumpy Skin Disease Virus (LSDV), and other poxviruses infecting cattle is very scant in Tanzania. The current study aimed to confirm and characterize LSDV and other poxviruses infecting cattle, from LSD suspected outbreaks in Tanzania. Methods: A total of 24 samples were collected from four LSD suspected outbreaks reported in Tanzania between February and May 2023. Samples were screened for LSDV genome by real-time PCR and then subjected to a high-resolution multiplex melting (HRM) assay where 10 samples were positive for Capripoxvirus (CaPV) and one sample was Parapoxvirus (PPV) positive. Four LSDV genes; RPO30, GPCR, EEV glycoprotein and B22R and the partial B2L gene of PPVs were analyzed. Results: All targeted LSDV genes from the Tanzanian isolates showed 100% similarity and isolates clustered with commonly circulating LSDV field isolates. Furthermore, the single nucleotide polymorphism (SNP) at position 240 (A-> G) of the EEV gene differentiates the Tanzanian LSDVs from the group of ancient Kenyan LSDV isolates while the B22R sequences of the Tanzanian LSDV isolates differed from the LSDV Neethling and LSDV KSGP-0240 derived vaccines. Sequence analysis of the partial B2L gene of the Tanzanian parapoxvirus bovinestomatitis, formerly known as Bovine papular stomatitis virus (BPSV) showed a different BPSV strain circulating compared to publicly available sequences. Conclusion: These findings confirm the presence of LSDV in Tanzania, which suggesting the need for establishing an effective control program and continuous monitoring. The presence of a typical profile for Tanzania BPSV is an indication that, although never reported before, BPSV is established in the country therefore this virus should be included in the differential diagnosis of LSDV. [ABSTRACT FROM AUTHOR]

Background: The study of rodent malaria parasites has significantly advanced our understanding of malaria parasite biology and host responses to parasite infections. There are four well-characterized rodent malaria parasite species (Plasmodium yoelii, P. chabaudi, P. berghei, and P. vinckei). Each species also has multiple strains that cause different disease phenotypes. P. yoelii nigeriensis N67C and N67, two isogenic parasites, are particularly intriguing as they differ in virulence and incite different immune responses in mice. The genome of the N67 parasite has been assembled recently, but not that of N67C. This study used PacBio HiFi sequencing data to assemble the N67C genome, compared the two genomes, and performed RNA sequencing to identify polymorphisms and differentially expressed genes (DEGs). Results: The assembled N67C parasite genome consisted of 16 scaffolds and three contigs of approximately 22.5 Mb with 100% and 96.6% completeness based on well-characterized single-copy orthologs specific to the Apicomplexa phylum and the Plasmodium genus, respectively. A comparison between the annotated N67C and N67 genomes revealed 133 single nucleotide polymorphisms (SNPs) and 75 indels. Among the polymorphic sites, an S (N67) to N (N67C) amino acid substitution at position 114 (S114N) in the dihydrofolate reductase-thymidylate synthase (DHFR-TS) confers resistance to pyrimethamine in mice. Additionally, 60 differentially expressed single-copy genes (DEGs) were detected after comparing mRNA levels between the two parasites. Starting with the predicted and annotated 5,681 N67C and 5,749 N67 genes, we identified 4,641 orthogroups that included at least one gene from the four P. yoelii parasites (N67, N67C, 17X, and YM), whereas 758 orthogroups showed subspecies or strain-specific patterns. Conclusion: The identification of polymorphic sites between the N67 and N67C genomes, along with the detection of the DEGs, may provide crucial insights into the variations in parasite drug responses and disease severity between these two isogenic parasites. The functional characterization of these genetic differences and candidate genes will deepen our understanding of disease mechanisms and pave the way for developing more effective control measures against malaria. [ABSTRACT FROM AUTHOR]

The current investigation was undertaken to elucidate the population-stratifying and ancestry-informative markers in Indian, Chinese, and wild yak populations using whole genome resequencing (WGS) analysis while employing various selection strategies (Delta, Pairwise Wright's Fixation Index-FST, and Informativeness of Assignment) and marker densities (5–25 thousand). The study used WGS data on 105 individuals from three separate yak cohorts i.e., Indian yak (n = 29), Chinese yak (n = 61), and wild yak (n = 15). Variant calling in the GATK program with strict quality control resulted in 1,002,970 high-quality and independent (LD-pruned) SNP markers across the yak autosomes. Analysis was undertaken in toolbox for ranking and evaluation of SNPs (TRES) program wherein three different criteria i.e., Delta, Pairwise Wright's Fixation Index-FST, and Informativeness of Assignment were employed to identify population-stratifying and ancestry-informative markers across various datasets. The top-ranked 5,000 (5K), 10,000 (10K), 15,000 (15K), 20,000 (20K), and 25,000 (25K) SNPs were identified from each dataset while their composition and performance was assessed using different criteria. The average genomic breed clustering of Indian, Chinese, and wild yak cohorts with full density dataset (105 individuals with 1,002,970 markers) was 81.74%, 80.02%, and 83.62%, respectively. Informativeness of Assignment criterion with 10K density emerged as the best combination for three yak cohorts with 86.94%, 96.46%, and 98.20% clustering for Indian, Chinese, and wild yak, respectively. There was an average increase of 7.56%, 22.72%, and 30.35% in genomic breed clustering scores of Indian, Chinese, and wild yak cohorts over the estimates of the original dataset. The selected markers showed overlap multiple protein-coding genes within a 10 kb window including ADGRB3, ANK1, CACNG7, CALN1, CHCHD2, CREBBP, GLI3, KHDRBS2, and OSBPL10. This is the first report ever on elucidating low-density SNP marker sets with population-stratifying and ancestry-informative properties in three yak groups using WGS data. The results gain significance for application of genomic selection using cost-effective low-density SNP panels in global yak species. [ABSTRACT FROM AUTHOR]

Background: Chronic myeloid leukaemia (CML) is a type of blood cancer that begins in the hematopoietic stem cells. It is primarily characterized by a specific chromosomal aberration, the Philadelphia chromosome. While the fusion gene is a major contributor to CML, several other genes including ADGRE2, that are reported as highly expressed in hematopoietic stem cells and could be utilized as a therapeutic marker in leukemic patients are implicated in the disease's progression. Until recently, little research had been conducted to identify single nucleotide polymorphisms (SNPs) associated with CML. Therefore, this study aims to investigate the influence of non-synonymous variants on the structure and function of the gene encoding adhesion G protein-coupled receptor E2, ADGRE2, and to evaluate their association with CML and its clinical and pathological characteristics. Methods: Non-synonymous SNPs of ADGRE2 were retrieved from the ENSEMBL, COSMIC, and gnomAD genome browsers, and the pathogenicity of deleterious variants was assessed using several established computational tools, including SIFT, CADD, REVEL, PolyPhen, and MetaLR. Results: Various in silico analyses explored the impact of damaging SNP on the function, stability, and structure of EGF-like modules containing mucin-like hormone receptor-like2 (EMR2) protein encoded by the ADGRE2 gene. Genotype analysis was performed on collected blood samples, revealing that altered genotype TT of variant rs765071211 (C/T) was associated significantly with CML patients compared to the control. Further in vitro and in vivo analyses suggest that this SNP holds potential for clinical translation. [ABSTRACT FROM AUTHOR]

Background: Split hand/foot malformation (SHFM) is a congenital limb deficiency characterized by missing or shortened central digits. Several gene loci have been associated with SHFM. Identifying microduplications at the single-cell level is challenging in clinical practice, and traditional detection methods may lead to misdiagnoses in embryos and pregnant women. Results: In this research, we utilized a low cell count and whole-genome amplification products to employ single nucleotide polymorphism arrays, next-generation sequencing, and third-generation sequencing methods to detect copy number variants of microduplications in a SHFM3 case with limited DNA. Additionally, Karyomapping and combined linkage analysis were conducted to validate the results. Conclusions: This study establishes a new strategy for identifying microduplications or microdeletions at the single-cell level in clinical preimplantation genetic testing, enhancing the efficiency and accuracy of diagnosing microduplication or microdeletion diseases during IVF-PGT and prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background and aims: Diabetic kidney disease (DKD) is a common complication of type 2 diabetes mellitus (T2DM) that leads to systemic inflammation. Maternally expressed gene 3 (MEG3) is a tumor suppressor that is involved in inflammation regulation. The current study investigated the association between DKD and the prevalence of the single-nucleotide polymorphisms (SNPs) of MEG3. Methods: A total of 706 and 735 patients were included in the DKD and non-DKD groups, respectively. The five SNPs of MEG3, namely rs4081134 (G/A), rs10144253 (T/C), rs7158663 (G/A), rs3087918 (T/G), and rs11160608 (A/C), were genotyped using TaqMan allelic discrimination. Results: Our results revealed that, in the DKD group, the distribution of the GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.703, 95% CI: 0.506–0.975, P = 0.035). In addition, in the pre-ESRD DKD subgroup, the distribution of the TG + GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.637, 95% CI: 0.421–0.962, P = 0.032). In addition, among men in the DKD subgroup, the distribution of the GG genotype of the MEG3 SNP rs3087918 was significantly lower than that of the wild-type genotype (AOR: 0.630, 95% CI: 0.401–0.990, P = 0.045). Glycated hemoglobin (HbA1c) level was significantly higher in all T2DM patients with the wild-type genotype of the MEG3 SNP rs3087918 (P = 0.020). In addition, HbA1c levels were significantly higher in male patients and male DKD patients with the wild-type genotype of the MEG3 SNP rs3087918 (P = 0.032 and 0.031, respectively). Conclusion: MEG3 SNP rs3087918 is significantly less prevalent in patients with DKD, and the SNP rs3087918 of MEG3 is associated with lower HbA1c levels. [ABSTRACT FROM AUTHOR]

Background: Aging is an irreversible progressive decline in physical function. Graves' disease (GD) is a common cause of hyperthyroidism and is characterized by elevated levels of the thyroid hormone (TH). High TH levels are associated with aging and a shortened lifespan. The causal relationship between GD and aging has yet to be investigated. Methods: We used genome-wide association study (GWAS) datasets and Mendelian randomization (MR) analysis to explore the causal link between GD and aging. To assess the statistical power of instrumental variables (IVs), F-statistics and R2 were used. MR analysis was conducted using inverse-variance weighting (IVW), MR-Egger, weighted median, and weighted mode. The odds ratio (OR) and 95% CI were calculated to estimate the relative risk of GD to the outcomes. The Cochran Q test, I2, MR-PRESSO test, and MR-Egger regression intercept were calculated using statistical and leave-one-out analyses to test the heterogeneity, horizontal pleiotropy, and stability of the IVs on the outcomes. Results: F-statistics of the five IVs were greater than 10, and the R2 values ranged from 0.033 to 0.156 (R2 > 0.01). According to the results of the IVW analysis, GD had no causal effect on facial aging (p = 0.189), age-related macular degeneration (p = 0.346), and Alzheimer's disease (p = 0.479). There was a causal effect of GD on the remaining outcomes: telomere length (TL) (OR = 0.982; 95%CI:0.969–0.994; p = 0.004), senile cataract (OR = 1.031; 95%CI:1.002–1.060; p = 0.033), age-related hearing impairment (OR = 1.009; 95%CI:1.004–1.014; p = 0.001), chronic obstructive pulmonary disease (COPD) (OR = 1.055; 95%CI:1.008–1.103; p = 0.020), and sarcopenia (OR = 1.027; 95%CI:1.009–1.046; p = 0.004). Conclusions: GD accelerates the occurrence of age-related phenotypes including TL, senile cataracts, age-related hearing impairment, COPD, and sarcopenia. In contrast, there are no causal linkages between GD and facial aging, age-related macular degeneration, or Alzheimer's disease. Further experimental studies could be conducted to elucidate the mechanisms by which GD facilitates aging, which could help slow down the progress of aging. [ABSTRACT FROM AUTHOR]

Background: Brucellosis, a zoonotic disease in Türkiye, which has significant direct and indirect impacts on the healthcare system and livestock. This study, which aimed to investigate the differences among Brucella spp. isolates originating from different regions of Türkiye, for implications for public health and veterinary medicine. Method: Twenty-one isolates from ruminants and two isolates from humans obtained from various regions of Türkiye were utilized in the study. The isolates were identified and biotyped using traditional microbiological procedures, and whole-genome sequencing (WGS) was performed. This was followed by single nucleotide polymorphism (SNP)--based phylogenetic analysis and WGS-based analysis of virulence and resistance genes. Additionally, phenotypic antimicrobial resistance and phage susceptibilities were determined. The obtained data were then compared for concordance, ensuring the validity and reliability of the results. Results: Our study, employing culture methods, polymerase chain reaction (PCR), and WGS analyses, identified 11 Brucella melitensis (bv 3 (n = 9), one each bv 1 and bv 2) and 12 B. abortus (bv 3 (n = 11), bv 9 (n = 1)) isolates All B. abortus isolates were of bovine origin, while the B. melitensis isolates were from sheep (n = 7), goat (n = 1), ram (n = 1), and humans (n = 2). In the whole-genome SNP-based phylogenetic tree, all B. melitensis strains were found to be of the IIb subtype of genotype II associated with the Eastern Mediterranean lineage. Ten different genotypes were identified in the SNP analysis of the isolates, with a maximum SNP difference of 278 and a minimum SNP difference of 4 among these genotypes. According to the WGS-SNP-based phylogenetic tree of B. abortus isolates, they were grouped in clade C1. In the SNP analysis, where ten different genotypes were identified, the SNP difference among these genotypes was a maximum of 316 and a minimum of 6. In the in silico MLST analysis performed with WGS data, B. melitensis isolates were identified as ST8 and ST102 genotypes, while B. abortus isolates were identified as ST2 and ST3 genotypes. The dominant genotypes were ST8 for B. melitensis and ST2 for B. abortus, respectively. Virulence gene analysis conducted based on WGS data of the 23 B. abortus and B. melitensis isolates revealed 43 virulence gene-associated regions in all strains, irrespective of species, host, or isolation year. Although classical resistance-related genes were not detected by WGS-based antimicrobial resistance gene analysis, phenotypic resistance analysis revealed resistance to azithromycin, rifampin, and trimethoprim/sulfamethoxazole in B. abortus and B. melitensis isolates. Conclusion: Both B. melitensis and B. abortus were circulating species in animals and human. The dominant genotypes were ST8 for B. melitensis and ST2 for B. abortus, respectively. All B. melitensis strains were found to be of the IIb subtype of genotype II associated with the Eastern Mediterranean lineage, while B. abortus isolates, they were grouped in clade C1. Further, a comprehensive study with a sufficient number of isolates covering all regions of Türkiye would provide more accurate information about the current epidemiological situation in the country. [ABSTRACT FROM AUTHOR]

Objective: Ulcerative colitis (UC) and Hashimoto's thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. Methods: We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran's Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. Results: Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36–69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. Conclusion: Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells. [ABSTRACT FROM AUTHOR]

Objective: The connectivity and genetic structuring of populations throughout a region influence a species' resilience and probability of recovery from anthropogenic impacts. By gaining a comprehensive understanding of population connectivity, more effective management can be prioritized. To assess the connectivity and population genetic structure of a common cold-water coral species, Desmophyllum pertusum (Lophelia pertusa), we performed Restriction-site Associated DNA Sequencing (RADseq) on individuals from nine sites ranging from submarine canyons off New England to the southeastern coast of the United States (SEUS) and the Gulf of Mexico (GOM). Fifty-seven individuals and 3,180 single-nucleotide polymorphisms (SNPs) were used to assess genetic differentiation. Results: High connectivity exists among populations along the SEUS, yet these populations were differentiated from those to the north off New England and in Norfolk Canyon along the North Atlantic coast of the United States, as well as those in the GOM. Interestingly, Norfolk Canyon, located just north of North Carolina, and GOM populations exhibited low levels of genetic differentiation, corroborating previous microsatellite analyses and signifying gene flow between these populations. Increasing sample sizes from existing populations and including additional sampling sites over a larger geographic range would help define potential source populations and reveal fine-scale connectivity patterns among D. pertusum populations. [ABSTRACT FROM AUTHOR]

Background: Genetic factors, including the Hedgehog Interacting Protein (HHIP) gene, play a crucial role in Chronic Obstructive Pulmonary Disease (COPD) susceptibility. This study examines the association between HHIP gene polymorphisms and COPD susceptibility, phenotypes, and serum IL-17 and IL-18 levels in a Han Chinese population. Methods: A case-control study was conducted with 300 COPD patients and 300 healthy controls in Chinese Han population. Participants underwent genotyping for HHIP gene polymorphisms, pulmonary function tests, and quantitative CT scans. DNA samples were sequenced using a custom chip targeting the HHIP gene. Serum IL-17 and IL-18 levels were measured by enzyme-linked immunosorbent assay. Associations between SNPs, COPD susceptibility, and phenotypes were analyzed using logistic and multiple linear regression models, adjusting for confounders. Results: Our study identified the rs11100865 polymorphism in the HHIP gene as significantly associated with COPD susceptibility (OR 2.479, 95% CI 1.527–4.024, P = 2.39E-04) after screening 114 SNPs through rigorous quality control. Stratified analyses further indicated this association was particularly in individuals aged 60 or older. Serum levels of IL-17 and IL-18 were significantly elevated in COPD patients compared to controls, with rs11100865 showing a notable association with IL-18 levels (B = 49.654, SE = 19.627, P = 0.012). However, no significant associations were observed between rs11100865 and serum IL-17 levels, COPD-related imaging parameters, or clinical phenotypes. Conclusion: This study identified a significant association between HHIP gene polymorphisms and COPD susceptibility in a Han Chinese population, with connections to inflammation, but found no significant associations between this SNP and COPD-related imaging or clinical phenotypes. Trial registration: www.chictr.org.cn ID: ChiCTR2300071579 2023-05-18. [ABSTRACT FROM AUTHOR]

Objective: To analyze the genotypes of VZV in Jiangsu province to identify vaccine strains and wild strains, providing a molecular biological background for the effective prevention and control of varicella. Method: Stratified sampling was used to collect herpes fluid or throat swab from patients diagnosed with varicella. ORF22 was carried out, and the restriction enzyme site of ORF38, ORF54 and ORF62 were detected. Results: All 207 virus strains were Clade 2 type by sequencing the PCR products of ORF22. The sequencing results showed that five SNP sites changed compared to the Dumas reference strain(Clade 1). From A to G at 37,902, from T to c at 38,055, from A to C at 38,081, and from G to A at 38,177, from G to A at 39,394. The prevalent VZV genotypes in Jiangsu is consistent with the P-Oka. The restriction enzyme site analysis of PCR amplification products from ORF38 (PstI), ORF54 (BglI), ORF62 (SmaI) showed that all 207 virus strains were wild-type. There were two different types of the wild strains, and 183 strains (88.4%) were PstI (+), BglI (+), SmaI (-). The wild strains between different regions showed no significant differences (χ2 = 0.05, P = 0.982). Conclusions: The prevalent VZV genotypes are Clade 2 and the prevalent virus strains are wild strains in Jiangsu Province, the primary wild strain observed is mainly PstI (+), BglI (+), SmaI (-). [ABSTRACT FROM AUTHOR]

Background: One of the main causes of health-related issues in children is neurodevelopmental disorders (NDDs), which include attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and Tourette syndrome (TS). Nonetheless, there is relatively little prior research looking at the link between immunological inflammation and NDDs. Our work uses a two-sample Mendelian Randomization (MR) approach to provide a thorough evaluation of the causal effects of immune traits on ADHD, ASD, and TS. Methods: As exposures, 731 immunological traits' genetic associations were chosen, and the outcomes were genome-wide association data for ADHD, ASD, and TS. The inverse-variance weighted (IVW), weighted median (WM), and MR-Egger methods were used to conduct MR analysis. The results' robustness, heterogeneity, and horizontal pleiotropy were confirmed using extensive sensitivity analysis. Results: With single-nucleotide polymorphisms serving as instruments and false discovery rate (FDR) correction applied, the study found that significantly higher expression of CD62L on CD62L+ myeloid DC (IVW, OR: 0.926, 95% CI 0.896~0.958, P = 9.42 × 10–6, FDR = 0.007) and suggestively higher absolute cell count (AC) of CD28 + DN (CD4-CD8-) (IVW, OR: 0.852, 95% CI = 0.780 ∼ 0.932, P-value = 4.65 × 10−4, FDR = 0.170) was associated with a lower risk of ADHD. There was no pleiotropy, and the causal relationships were strong according to sensitivity, leave-one-out, and MR-Steiger directionality tests. For ASD and TS, no harmful or protective immune traits were observed. Conclusions: The results of the study lend credence to the theory that deficiency in CD62L on CD62L+ myeloid DC and CD28 + DN (CD4-CD8) AC may contribute to the onset of ADHD. [ABSTRACT FROM AUTHOR]

Purpose: In the Zhejiang region, research on Helicobacter pylori is lacking. The purpose of this study was to assess the extent of antibiotic resistance in H. pylori in this region, explore alternative methods for predicting the resistance patterns of H. pylori, and investigate the colonization of native gastric mucosa by other clades of H. pylori in the structure population of this bacterium. Methods: Strains were cultured under microaerobic conditions, and antimicrobial susceptibility testing (AST) was performed via agar dilution. Whole-genome sequencing (WGS) was performed via next-generation sequencing (NGS) technology. Epidemiological data including data from this study and reported articles from Zhejiang, China, were included. Further analyses based on AST, WGS, and epidemiological date include virulence genes, antibiotic resistance-related mutations, and phylogenetic trees based on 7 housekeeping genes and core-genome single nucleotide polymorphisms (SNPs). Results: The bacterial isolates in this study presented higher antibiotic resistance rates than previously reported, especially against levofloxacin and clarithromycin. The point mutation A2147G in 23 S rRNA is specific to clarithromycin resistance. Mutations at position/s 87 and/or 91 of the gyrA gene amino acid sequence are highly consistent with levofloxacin resistance highly. The point mutations C1707T in 23 S rRNA and E463K in the gyrB gene have not been previously documented in China. All the bacterial isolates belong to Asian branches in the structure population. The resistance rate to clarithromycin of isolates from hosts born after January 1, 1977 is statistically higher than that of hosts born before 1977. Conclusion: Eradication therapy based on AST results is urgently needed in Zhejiang. The point mutation A2147G in 23 S rRNA and point mutations in the gyrA gene at amino acid/s 87 and/or 91 are sufficient for predicting resistance to clarithromycin and levofloxacin, respectively. The isolate with the mutation E463K in the gyrB gene represents a significant contribution to the field. Mutations in 23 S rRNA may offer valuable insights into the dynamics of H. pylori transmission among hosts. [ABSTRACT FROM AUTHOR]

Background and objective: Genetic polymorphism studies in families and twins indicated the heritability of depression. However, the association between genes with genetic polymorphism and depression provides various findings and remains unclear. Therefore, we conducted a systematic review and meta-analysis to determine the genes with their polymorphism associated with the symptomatic depression known as major depressive disorder (MDD). Materials and methods: PubMed and Scopus were searched for relevant studies published before May 22, 2023 (1968–2023), and 62 were selected for this review. The study's bias risk was investigated using the Newcastle–Ottawa scale. Gene functional enrichment analysis was investigated for molecular function (MF) and biological process (BP) and pathways. A meta-analysis of the studied genes that were replicative in the same single nucleotide polymorphism was conducted using a random-effect model. Results: The 49 genes involved in MDD were studied and engaged in several pathways, such as tryptophan metabolism or dopaminergic and serotonergic synapses. Based on gene overlapping in MF and BP, 13 genes with polymorphisms were identified as related to MDD. Most of them were only studied once. Solute carrier family 6 member 4 (SLC6A4) overlapping between MF and BP and brain-derived neurotrophic factor (BDNF) as unique to BP were replicative studied and used in the meta-analysis. The polymorphism of SLC6A4 SS and LS genotypes increased the occurrence of MDD development but not significantly [odd ratio (OR) = 1.39; 95% confidence interval (CI) = 0.87–2.22; P = 0.16 and OR = 1.13; 95% CI = 0.84–1.53; P = 0.42, respectively]. A similar result was observed for BDNF rs6265 GG (OR = 1.26; 95% CI = 0.78–2.06; P = 0.35) and BDNF rs6265 AA genotypes (OR = 1.12; 95% CI = 0.77–1.64; P = 0.56). These studies indicated low bias and significant heterogeneity. Conclusion: At least 13 studied genes with polymorphisms were involved in MDD development according to MF and BP, but not significantly. These results suggest that MDD development risk factors might require genetic and other factors for interaction and induction. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a debilitating mental disorder affecting about 1% of the global population, characterized by significant cognitive impairments and a strong hereditary component. Carnitine, particularly Levo-carnitine and its derivatives, plays a crucial role in cellular metabolism and mitochondrial function, with evidence suggesting a link between levo-carnitine deficiency and schizophrenia pathology. This study aims to investigate the causal relationship between different subtypes of levo-carnitine and the susceptibility to schizophrenia using Mendelian randomization analysis. Methods: Forward Mendelian randomization analysis was conducted using levo-carnitine and its derivatives as exposure and schizophrenia as the outcome. Candidate data were obtained from the Open-GWAS database. Instrumental variables were identified as single nucleotide polymorphisms closely associated with exposure and harmonized with the outcome data after removing confounders and outliers. Mendelian randomization analysis was performed using inverse variance weighting as the primary approach, and sensitivity analysis was conducted to assess the reliability and robustness of the results. Finally, a reverse Mendelian randomization analysis was carried out using the same analytical procedures. Results: The Mendelian randomization results indicate a significant negative causal relationship between isovaleryl-levo-carnitine and schizophrenia (P < 0.05), but no significant associations in other groups (P > 0.05). Additionally, the reverse Mendelian randomization analysis did not identify any causal relationship between schizophrenia and levo-carnitine related exposures (P > 0.05). Sensitivity analyses, including pleiotropy and heterogeneity analysis, did not reveal any potential bias in the Mendelian randomization results (P > 0.05). Conclusion: The results suggest that elevated levels of isovaleryl-levo-carnitine may potentially mitigate the risk of developing schizophrenia, highlighting the prospective therapeutic and preventive implications of isovaleryl-levo-carnitine in the clinical management of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: At present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT. Methods: In this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations. Results: With IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin. Conclusions: In this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of lung adenocarcinoma (LUAD), the most prevalent histological subtype of primary lung cancer, remains inadequate, with accurate prognostic assessment posing significant challenges. This study sought to elucidate the prognostic significance of mitochondrial-related genes in LUAD through an integrative multi-omics approach, aimed at developing personalized therapeutic strategies. Utilizing transcriptomic and single-cell RNA sequencing (scRNA-seq) data, alongside clinical information from publicly available databases, we first applied dimensionality reduction and clustering techniques to the LUAD single-cell dataset, focusing on the subclassification of fibroblasts, epithelial cells, and T cells. Mitochondrial-related prognostic genes were subsequently identified using TCGA-LUAD data, and LUAD cases were stratified into distinct molecular subtypes through consensus clustering, allowing for the exploration of gene expression profiles and clinical feature distributions across subtypes. By leveraging an ensemble of machine learning algorithms, we developed an Artificial Intelligence-Derived Prognostic Signature (AIDPS) model based on mitochondrial-related genes and validated its prognostic accuracy across multiple independent datasets. The AIDPS model demonstrated robust predictive power for LUAD patient outcomes, revealing significant differences in responses to immunotherapy and chemotherapy, as well as survival outcomes between risk groups. Furthermore, we conducted comprehensive analyses of tumor mutation burden (TMB), immune microenvironment characteristics, and genome-wide association study (GWAS) data, providing additional insights into the mechanistic roles of mitochondrial-related genes in LUAD pathogenesis. This study not only offers a novel approach to improving prognostic assessments in LUAD but also establishes a strong foundation for the development of personalized therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Cabbage (Brassica oleracea L. var. capitata) is an important crop within the Brassica oleracea species and is extensively cultivated worldwide. In recent years, outbreaks of downy mildew caused by Hyaloperonospora parasitica have resulted in substantial losses in cabbage production. Despite this, there have been limited studies on genes associated with resistance to downy mildew in cabbage. Results: This study identified sister lines exhibiting significant differences in disease resistance and susceptibility. Using bulked segregant analysis followed by sequencing (BSA-seq) and linkage analysis, the cabbage resistance locus BoDMR2 was accurately mapped to an approximately 300 kb interval on chromosome 7. Among the candidate genes identified, several single nucleotide polymorphisms (SNPs) and a 3-bp insertion were found within the conserved domain of the Bo7g117810 gene, encoding a leucine-rich repeat domain protein, in susceptible genotypes. Additionally, real-time quantitative polymerase chain reaction (RT‒qPCR) analysis revealed that the expression level of Bo7g117810 in resistant specimens was 2.5-fold higher than that in susceptible specimens. An insertion‒deletion (InDel) marker was designed based on the identified insertion in susceptible materials, facilitating the identification and selection of downy mildew-resistant cabbage cultivars. Conclusions: This study identifies Bo7g117810 as a potential candidate gene associated with adult-stage resistance to downy mildew in cabbage, supported by observed differences in gene sequence and expression levels. Furthermore, the development of an InDel marker I1-3, based on its mutation, provides valuable resources for breeding resistant cabbage cultivars. [ABSTRACT FROM AUTHOR]

Background: Certain structural variants (SVs) including large-scale genetic copy number variants, as well as copy number-neutral inversions and translocations may not all be resolved by chromosome karyotype studies. The identification of genetic risk factors for Parkinson's disease (PD) has been primarily focused on the gene-disruptive single nucleotide variants. In contrast, larger SVs, which may significantly influence human phenotypes, have been largely underexplored. Optical genomic mapping (OGM) represents a novel approach that offers greater sensitivity and resolution for detecting SVs. In this study, we used induced pluripotent stem cell (iPSC) lines of patients with PD-linked SNCA and PRKN variants as a proof of concept to (i) show the detection of pathogenic SVs in PD with OGM and (ii) provide a comprehensive screening of genetic abnormalities in iPSCs. Results: OGM detected SNCA gene triplication and duplication in patient-derived iPSC lines, which were not identified by long-read sequencing. Additionally, various exon deletions were confirmed by OGM in the PRKN gene of iPSCs, of which exon 3–5 and exon 2 deletions were unable to phase with conventional multiplex-ligation-dependent probe amplification. In terms of chromosomal abnormalities in iPSCs, no gene fusions, no aneuploidy but two balanced inter-chromosomal translocations were detected in one line that were absent in the parental fibroblasts and not identified by routine single nucleotide variant karyotyping. Conclusions: In summary, OGM can detect pathogenic SVs in PD-linked genes as well as reveal genomic abnormalities for iPSCs that were not identified by other techniques, which is supportive for OGM's future use in gene discovery and iPSC line screening. [ABSTRACT FROM AUTHOR]

Malaria remains a key health and economic problem, particularly in sub-Saharan Africa. The emergence of artemisinin drug resistance (ART-R) parasite strains poses a serious threat to the control and elimination of this scourge. This is because artemisinin-based combination therapies (ACTs) remain the first-line treatment in the majority of malaria-endemic regions in Sub-Saharan Africa. Certain single-nucleotide polymorphisms in the propeller domains of Plasmodium falciparum Kelch 13 protein (K13) have been associated with delayed parasite clearance in vivo and in vitro. These mutations serve as vital molecular markers for tracking the emergence and dispersion of resistance. Recently, there have been increasing reports of the emergence and spread of P. falciparum ART-R parasites in the Eastern Africa region. This necessitates continued surveillance to best inform mitigation efforts. This study investigated the presence of all reported mutations of K13 propeller domains in the parasite population in Busia County, Kenya, a known malaria-endemic region. Two hundred twenty-six participants with microscopically confirmed uncomplicated malaria were recruited for this study. They were treated with artemether–lumefantrine under observation for the first dose, and microscopic examination was repeated 1 day later after ensuring the participants had taken the second and third doses. P. falciparum DNA from all samples underwent targeted amplification of the K13 gene using a semi-nested PCR approach, followed by Sanger sequencing. The recently validated ART-R K13 mutation C469Y was identified in three samples. These three samples were among 63 samples with a low reduction in parasitemia on day 1, suggesting day 1 parasitemia reduction rate is a useful parameter to enrich the ART-R parasites for further analysis. Our findings highlight the need for continuous surveillance of ART-R in western Kenya and the region to determine the spread of ART-R and inform containment. [ABSTRACT FROM AUTHOR]

Mathematical ability is influenced by genes and environment. This study focused on the effect of DRD2, a candidate gene for working memory, on mathematical ability. The results in child participants revealed associations between the DRD2 gene and mathematical ability. It was found that individual's mathematical ability was influenced by Single Nucleotide Polymorphisms (SNPs) in DRD2, both in the form of haplotypes and in the way of interaction with parental education. These findings suggest that dopaminergic genes are linked to mathematical ability. This study provides evidence for the genetic basis of mathematical ability and offers guidance for personalized intervention in mathematical education. [ABSTRACT FROM AUTHOR]

Non-typhoidal Salmonella (NTS) is one of the top causes of diarrhea worldwide. Ceftriaxone is commonly recommended as the initial treatment option for Salmonella infections due to its antibacterial effectiveness. The objective of this study was to investigate the molecular epidemiological characteristics of NTS and to compare the phenotypic and genotypic profiles of antimicrobial resistance in multidrug-resistant Salmonella strains by sequencing 329 NTS strains collected from a county-level hospital between 2018 and 2021. Multi-locus sequence typing (MLST), antimicrobial resistance genes and plasmid types were identified by BacWGSTdb 2.0 webserver. Phylogenetic analysis of all NTS strains was carried out using Snippy and Gubbins software. The transferability of ceftriaxone resistant plasmids was confirmed through plasmid conjugation assays, and verified by S1-PFGE-Southern blot assays. The predominant serotypes among all NTS strains were Typhimurium (161/329), Enteritidis (49/329) and London (45/329). The most common sequence type observed was ST34 (86/329), followed by ST19 (72/329) and ST11 (47/329). The antimicrobial resistance of Salmonella to a wide range of antimicrobials showed an overall increase. Out of these 37 (11.24%) ceftriaxone-resistant strains, with the majority of them (33/37) being blaCTX−M. The predominant plasmid types identified were IncHI2 (14/21) and IncI1 (6/21), ranging in size from 70 kb to 360 kb. The conjugation efficiency was calculated with the high conjugation efficiency of 1.1 × 10− 5 to 9.3 × 10− 2. The strains varied widely, ranging from 3 to 45,024 single nucleotide polymorphisms (SNPs). There are close linkages observed among the predominant lineage, with an average of 78 SNPs between each pair of ST34 strains. The findings contribute to our understanding of the transmission and resistance mechanisms of multidrug-resistant Salmonella, thereby facilitating the development of effective control strategies. [ABSTRACT FROM AUTHOR]

Trimming adapters and low-quality bases from next-generation sequencing (NGS) data is crucial for optimal analysis. We evaluated six trimming programs, implementing five different algorithms, for their effectiveness in trimming adapters and improving quality, contig assembly, and single-nucleotide polymorphism (SNP) quality and concordance for poliovirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and norovirus paired data sequenced on Illumina iSeq and MiSeq platforms. Trimmomatic and BBDuk effectively removed adapters from all datasets, unlike FastP, AdapterRemoval, SeqPurge, and Skewer. All trimmers improved read quality (Q ≥ 30, 87.8 − 96.1%) compared to raw reads (83.6 − 93.2%). Trimmers implementing traditional sequence-matching (Trimmomatic and AdapterRemoval) and overlapping algorithm (FastP) retained the highest-quality reads. While all trimmers improved the maximum contig length and genome coverage for iSeq and MiSeq viral assemblies, BBDuk-trimmed reads assembled the shortest contigs. SNP concordance was consistently high (> 97.7 − 100%) across trimmers. However, BBDuk-trimmed reads had the lowest quality SNPs. Overall, the two adapter trimmers that utilized the traditional sequence-matching algorithm performed consistently across the viral datasets analyzed. Our findings guide software selection and inform future versatile trimmer development for viral genome analysis. [ABSTRACT FROM AUTHOR]

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs). Method: In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed. Results: Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer's disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10–3) in PSP. Conclusions: Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: The burden of sepsis worsens due to the continuation of emerging pathogens such as multidrug-resistant Pantoea species. Methods: A multicenter study was conducted between October 2019 and September 2020 at four hospitals located in central, southern, and northern parts of Ethiopia. A total of 1416 sepsis patients were recruited and blood cultures were performed. At each study site, positive cultures were characterized by their colony characteristics, gram stain, and conventional biochemical tests. All Pantoea species were identified using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI TOF) and subjected to whole genome sequencing (WGS) using Illumina HiSeq 2500. The phylogeny structure of Pantoea isolates was calculated using IQ-TREE v1.6.12 from single-nucleotide polymorphisms detected by Snippy v.4.6.0 and filtered by Gubbins v.2.3.4. Average nucleotide identity was estimated by using OrthoANI v.0.93.1 on Shovill v.1.1.0 assemblies. Antimicrobial resistance genes and plasmid replicons were detected using ARIBA v.2.14.6. Phylogenetic trees were visualized using iTOLv.6.5.2. Results: Multiple Pantoea species include: P. dispersa (n = 19), P. septica (n = 1), and a novel Pantoea spp. (n = 1), were identified among sepsis patients. All P. dispersa isolates and the novel Pantoea species were isolated at Dessie Referral Hospital and displayed phylogenetic clonality, including the ubiquity of an IncM1 plasmid and identical antimicrobial resistance (AMR) gene profiles, encoding blaCTX−M−15, blaTEM−1D, blaSCO−1, and aac(3)-lla. The novel Pantoea spp. isolate harboured blaCTX−M−9 and blaTEM−1D and carried an IncN3 plasmid replicon. The P. septica was isolated at Tikur Anbessa Specialized Hospital in Addis Ababa and carried no detectable acquired AMR genes. Conclusion: The emerging Pantoea spp. carrying multiple AMR genes were identified from sepsis patients. Implementation of strong infection prevention strategies and building surveillance capacity with advanced bacteriology laboratories capable of identifying multidrug-resistant emerging pathogens is strongly recommended. [ABSTRACT FROM AUTHOR]

Background: Tibetan highlanders have adapted to hypoxic environments through genetic mechanisms that avoid hemoglobin concentration increases and prevent polycythemia. Recently, sex differences in hemoglobin dynamics with age have been reported among Tibetan highlanders living in Tsarang. Additionally, concerns have been raised that dietary changes associated with modernization may increase the risk of polycythemia and lifestyle-related diseases among Tibetan highlanders. However, the relationship between genetic polymorphisms and the risk of lifestyle-related diseases in Tibetan highlanders has been investigated in only a few regions. This study aims to elucidate whether polymorphisms in genes related to hypoxic adaptation are associated with the incidence of lifestyle-related diseases and polycythemia and whether these polymorphisms affect hemoglobin dynamics in the residents of Tsarang, Mustang, Nepal. Methods: Health checkup data from individuals living in Tsarang in Mustang District, Nepal, collected in 2017, were used to determine the prevalence of obesity, hypertension, diabetes, hypoxemia, and polycythemia. DNA was extracted from whole-blood samples, and data for the single-nucleotide polymorphisms (SNPs) rs13419896 (EPAS1), rs12619696 (EPAS1), and rs2790859 (EGLN1) were obtained using real-time PCR. The health checkup data were statistically analyzed to determine the associations of these diseases with polymorphisms in genes related to hypoxic adaptation. Results: A total of 168 participants, comprising 78 males and 90 females, were included in the final analysis. In terms of the prevalence of each disease, only the prevalence of polycythemia significantly differed between sexes (p < 0.01). Additionally, among the three analyzed SNPs, significant sex differences in genotype frequency were observed for rs13419896 and rs2790859. For rs2790859 in females, Tibetan highlanders with the adaptive genotype had a significantly lower incidence of polycythemia (p < 0.01) and significantly lower hemoglobin concentrations (p < 0.01). Conclusions: This study revealed that there are sex differences in the genotype frequency of gene-related hypoxic adaptations among the residents of Tsarang. The findings also suggested that the rs2790859 polymorphism might be involved in the recent incidence of polycythemia among Tsarang residents. If the frequency of non-Tibetan genotypes increases due to intermixing with other populations in the Mustang District, polycythemia may emerge as a modern disease. It is essential to continue investigating the health status of Mustang residents to elucidate various aspects of hypoxic adaptation and disease susceptibility. [ABSTRACT FROM AUTHOR]

Background: Previous studies have found that patients with epilepsy are more likely to suffer impulsivity. However, the causal relationship between impulsivity and epilepsy is unknown. In this study, we conduct a bidirectional Mendelian randomization (MR) study to explore the causal relationship between impulsivity and epilepsy with recurrent seizure. Methods: Data of the genome-wide association studies (GWAS) on 14 impulsivity traits and epilepsy were obtained from the GWAS catalog and UK Biobank. Inverse-variance weighted (IVW) and weighted median (WM) methods were utilized for MR estimates. IVW, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) methods were used to assess heterogeneity and pleiotropy. Results: Single-nucleotide polymorphisms (SNPs) related to the lack of perseverance were associated with a decreased risk of epilepsy with recurrent seizures according to the results of IVW (odd ratio [OR] = 0.93, 95% confident interval [CI] = 0.90–0.97, P = 0.001) and WM (OR = 0.93, 95%CI = 0.87–0.98, P = 0.007). Meanwhile, heterogeneity was not observed with a Cochran Q-derived P value of 0.819 for MR egger and a P value of 0.808 for IVW. Pleiotropy was not found according to the MR-PRESSO (P = 0.273). The other 13 impulsivity traits had no causal effect on epilepsy with recurrent seizures. Meanwhile, SNPs related with epilepsy with recurrent seizures had no causal effect on the 14 impulsivity traits. Conclusions: This MR study suggests that lack of perseverance may be a protective factor against epilepsy with recurrent seizures. However, epilepsy with recurrent seizures does not affect impulsivity. [ABSTRACT FROM AUTHOR]

Background: Despite the fact that diarrhea is more accurately described as a clinical symptom than a disease. Diarrhea is one of the most important issues in ovine medicine, particularly in lambs, and because of high morbidity and mortality rate, sluggish growth performance, and veterinary costs, it is believed to be a major source of economic loss. Salmonella and enterotoxigenic Escherichia coli are the most common and commercially significant agents responsible for diarrhea. Objective: The objective of this study was to monitor the nucleotide sequence variations, gene expression, serum inflammatory and oxidative stress biomarkers in diarrheic lambs. Another aim was to identify different pathotypes and virulence genes of Salmonella and E. coli causing diarrhea. Methodology: Blood samples were taken from 50 Barki who were diarrheal and 50 who appeared to be healthy, and then divided in 3 portions, with EDTA added to the first part for CBC, DNA and RNA extraction. The second sample received 5000 I.U. of heparin calcium, and a clean plain tube was used for the third component. The second and third sections were centrifuged to extract serum and plasma until the biochemical and immunological analysis was completed. Fecal samples were collected for bacteriological examination, and the bacteria were identified by PCR analysis. PCR-DNA sequencing was conducted for immune (SELL, JAK2, SLC11A1, IL10, FEZF1, NCF4, LITAF, SBD2, NFKB, TNF-α, IL1B, IL6, LGALS, and CATH1), antioxidant (SOD1, CAT, GPX1, GST, Nrf2, Keap1, HMOX1, and NQO1), and GIT health (CALB1, GT, and MUC2) genes in healthy and diarrheic lambs. Results: Virulent genetic markers of pathogenic characteristics of E. coli (astA, Vt2e (Stx2e), CFA/I, groES and luxS) and Salmonella (invA, SopB, bcfC and avrA) were detected in all diarrheic lambs. PCR-DNA sequencing of immune, antioxidant and intestinal health genes found eleven single nucleotide polymorphisms (SNPs) linked to either diarrhea resistance or susceptibility in Barki lambs. Transcript levels of immune, antioxidant, and GIT health (CALB1, GT, and MUC2) genes varied between healthy and diarrheic lambs. Nucleotide sequence variation of the genes under inquiry between reference sequences in GenBank and those of the animals under investigation verified all identified SNPs. Significant (P = 0.001) erythrocytosis, neutrophilic leukocytosis, with lymphocytopenia were observed in diarrheic lambs. Significant (P = 0.001) increases in serum IL-1α, IL-1β, IL-6, TNF-α (90.5 ± 1.7, 101.8 ± 1.7, 72.3 ± 6.6, 71.26 ± 4.89 Pg/ml, respectively), serum Fb, Cp, Hp, SAA (230.7 ± 12.4 mg/dl, 6.5 ± 0.07 mg/dl, 2.5 ± 0.09 g/dl, 7.4 ± 0.4 mg/L, respectively), free radicals (MDA, NO), cortisol (6.91 ± 0.18 μg/dl) and growth hormone, with significant (P = 0.001) decreases in serum IL-10 (81.71 ± 1.05 Pg/ml), antioxidants (CAT, GPx), insulin, triiodothyronine (T3) and thyroxine (T4) in diarrheic lambs. Conclusions: The study's findings provided credence to the theory that marker-assisted selection (MAS) could be used to predict and prevent diarrhea in Barki sheep by selecting lambs based on SNPs in genes linked to inflammation, antioxidants, and intestinal health. In order to establish an efficient management protocol and determine the most susceptible risk period for disease occurrence, gene expression profiles of the genes under investigation, pro-inflammatory cytokines and acute phase proteins may also be utilized as proxy biomarkers for lamb enteritis. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence supports the comorbidity between depression (DEP) and obesity, yet the genetic mechanisms underlying this association remain unclear. Our study explored the shared genetic architecture and causal associations of DEP with BMI. Methods: We investigated the multigene overlap and genetic correlation between DEP (N > 1.3 million) and BMI (N = 806,834) based on genome-wide association studies (GWAS) and using the bivariate causal mixture model and linkage disequilibrium score regression (LDSC). The causal association was explored by bi-directional Mendelian randomization (MR). Common risk loci were identified through cross-trait meta-analyses. Stratified LDSC and multi-marker gene annotation analyses were applied to investigate single-nucleotide polymorphisms enrichment across tissue types, cell types, and functional categories. Finally, we explored shared functional genes by Summary Data-Based Mendelian Randomization (SMR) and further detected differential expression genes (DEG) in brain tissues of individuals with depression and obesity. Results: We found a positive genetic correlation between DEP and BMI (rg = 0.19, P = 4.07 × 10−26), which was more evident in local genomic regions. Cross-trait meta-analyses identified 16 shared genetic loci, 5 of which were newly identified, and they had influence on both diseases in the same direction. MR analysis showed a bidirectional causal association between DEP and BMI, with comparable effect sizes estimated in both directions. Combined with gene expression information, we found that genetic correlations between DEP and BMI were enriched in 6 brain regions, predominantly in the nucleus accumbens and anterior cingulate cortex. Moreover, 6 specific cell types and 23 functional genes were found to have an impact on both DEP and BMI across the brain regions. Of which, NEGR1 was identified as the most significant functional gene and associated with DEP and BMI at the genome-wide significance level (P < 5 × 10−8). Compared with healthy controls, the expression levels of NEGR1 gene were significant lower in brain tissues of individuals with depression and obesity. Conclusions: Our study reveals shared genetic basis underpinnings between DEP and BMI, including genetic correlations and common genes. These insights offer novel opportunities and avenues for future research into their comorbidities. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation is associated with the etiology of various cancers. However, there is a lack of systematic research in urologic cancers. This study aims to use a two-sample Mendelian randomization (MR) approach to evaluate the role of circulating cytokines in the development of urologic cancers. Methods: We obtained the summary-level data for bladder cancer (373,295 cases and 372,016 controls), prostate cancer (462,933 cases and 459,664 controls), and kidney cancer (463,010 cases and 461,896 controls) from the UK Biobank. Genetic variations linked to 41 circulating cytokines were used as instrumental variables (IVs) in meta-analyses of genome-wide association studies (GWASs) involving 8,293 individuals from Finland. We primarily used the inverse-variance weighted (IVW) method to assess the potential associations between the 41 cytokines and the risk of 3 common urologic cancers. Weighted-median method, weighted mode and simple-median method were used to assess the sensitivity. Heterogeneity and pleiotropic outlier were evaluated by Cochran's Q test and MR-Egger regression. Genetic correlation, colocalization analysis and multivariable MR analysis were used to further validate the potential pleiotropy. Results: After the Bonferroni correction, there was an observed association between elevated genetically predicted levels of CCL27 and a heightened risk for bladder cancer. Conversely, IL-12p70 levels were found to have a protective association against the risk of bladder cancer. Sensitivity analyses utilizing various IV sets and MR approach remained robust. Furthermore, we found potential associations of 7 cytokines with urologic cancers (4.07 × 10−4 ≤ P < 0.05). Conclusion: Our study supported causal associations between CCL27, IL-12p70 and bladder cancer risk and potential associations of 7 cytokines with the risk of urologic cancers, helping us to further understand the pathogenesis of urologic cancers and providing clues for improving diagnostic accuracy and therapies. [ABSTRACT FROM AUTHOR]

Background: Research into the genetic diversity of honey bee (Apis melliferaL.) populations has become increasingly significant in recent decades, primarily due to population declines attributed to human activities and climate change. As a species of great importance, breeding programs that leverage understanding of genomic diversity could offer solutions to mitigate these challenges. The objective of this study was to examine the genomic diversity and population structure of Carniolan honey bees (Apis mellifera carnica) using the Illumina SNP chip on a large honey bee sample collected from Central and South-Eastern European countries. The study also aims to offer recommendations for future breeding programs. Results: Our analysis involved Discriminant Analysis of Principal Components (DAPC), heterozygosity, admixture analysis, fixation indices (FST), Neighbour-Joining tree, gene flow and Isolation-by-distance analysis. DAPC indicated distinct separation between the Carniolan and Italian honey bee (Apis mellifera ligustica) populations, whereas the admixture analysis revealed varying levels of gene flow and genetic admixture within the Carniolan honey bee populations, demonstrating closer relationships between specific geographic regions (confirmed by Isolation-by-distance analysis). Furthermore, the research of heterozygosity, genomic inbreeding, pairwise FST values, and Neighbour-Joining tree provided insights into the patterns of genetic differentiation and similarity among the populations of Carniolan honey bee within its natural habitat. We have observed genetic homogeneity of the Carniolan honey bee population when considered in a broader genetic/geographical context. However, the Carniolan honey bee has sufficient genetic diversity in its geographical home range that needs to be carefully monitored and maintained. Conclusions: This study provides important insights into the genetic composition, differentiation, and relationships among Carniolan honey bee populations in Central and South-Eastern European countries. The findings are crucial for conservation efforts, breeding programs, and sustainable beekeeping practices. They emphasise the importance of considering genetic factors and population structure in the breeding and management of honey bees. By understanding these genetic relationships, we can develop strategies to preserve genetic diversity, improve breeding outcomes, and ensure the resilience of honey bee populations in the face of environmental changes and challenges. This knowledge can also inform policy makers and stakeholders on best practices to maintain healthy bee populations, which are vital for ecosystem services and agricultural productivity. [ABSTRACT FROM AUTHOR]

Background: To investigate the association of vitamin D receptor (VDR) gene polymorphism with caries risk in children(< 18 years). Methods: The electronic databases PubMed, Cochrane, EMBASE, Web of Science, CNKI, Cqvip, and Wanfang were searched for observational studies on the relationship between VDR single nucleotide polymorphism(SNP) and caries, including cohort, case–control, and cross-sectional studies. Quality assessment of selected studies was conducted using the Newcastle Ottawa scale. Odds ratios (OR) with 95% confidence intervals (CI) values for associations of individual VDR SNP with dental caries were calculated based on four genetic models: allelic, recessive, dominant, and over-dominant. Results: Of 79 studies considered, 10 (nine case–control and one cross-sectional) were selected for analysis; the studies involved seven VDR SNPs: ApaI(rs7975232),BsmI(rs1544410),FokI(rs2228570),TaqI(rs731236), TaqI/BglI(rs739837), FokI(rs10735810) and Cdx-2(rs11568820). Alleles C and T of FokI(rs10735810) were significantly differently distributed in the caries and caries-free groups (OR = 1.33, 95% CI: 1.30–2.30, P = 0.03), with CC + CT genotypes at this locus associated with greater risk of developing caries than the TT genotype (OR = 1.87, 95%CI: 1.15–3.04, P = 0.01). Further, TT + CC genotype at TaqI(rs731236) was associated with a 1.33-fold higher risk of caries development than the TC genotype (OR = 1.33, 95%CI: 1.06–1.67, P = 0.02). On subgroup analysis, the association between TaqI(rs731236) and caries risk was affected by dentition type, and ethnicity (permanent dentition: OR = 1.48, 95%CI: 1.07–2.03, P = 0.02; Asian: OR = 1.38, 95%CI: 1.02–1.87, P = 0.03;). Genotype distributions at BsmI(rs1544410), TaqI/BglI(rs739837), FokI(rs2228570), and ApaI(rs7975232) did not differ significantly between the caries and caries-free groups. Conclusions: Caries risk could be associated with TaqI(rs731236) and FokI(rs10735810) genotypes, and TaqI(rs731236) may be a risk factor for permanent teeth caries among Asian people. [ABSTRACT FROM AUTHOR]

Angiogenesis-osteogenesis coupling is critical for proper functioning and maintaining the health of bones. Any disruption in this coupling, associated with aging and disease, might lead to loss of bone mass. Osteoporosis (OP) is a debilitating bone metabolic disorder that affects the microarchitecture of bones, gradually leading to fracture. Computational analysis revealed that normal angiogenesis is disrupted during the progression of OP, especially postmenopausal osteoporosis (PMOP). The genes associated with OP and PMOP were retrieved from the DisGeNET database. Hub gene analysis and molecular pathway enrichment were performed via the Cytoscape plugins STRING, MCODE, CytoHubba, ClueGO and the web-based tool Enrichr. Twenty-eight (28) hub genes were identified, eight of which were transcription factors (HIF1A, JUN, TP53, ESR1, MYC, PPARG, RUNX2 and SOX9). Analysis of SNPs associated with hub genes via the gnomAD, I-Mutant2.0, MUpro, ConSurf and COACH servers revealed the substitution F201L in IL6 as the most deleterious. The IL6 protein was modeled in the SWISS-MODEL server and the substitution was analyzed via the YASARA FoldX plugin. A positive ΔΔG (1.936) of the F201L mutant indicates that the mutated structure is less stable than the wild-type structure is. Thirteen hub genes, including IL6 and the enriched molecular pathways were found to be profoundly involved in angiogenesis/endothelial function and immune signaling. Mechanical loading of bones through weight-bearing exercises can activate osteoblasts via mechanotransduction leading to increased bone formation. The present study suggests proper mechanical loading of bone as a preventive strategy for PMOP, by which angiogenesis and the immune status of the bone can be maintained. This in silico analysis could be used to understand the molecular etiology of OP and to develop novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Fritillariae Cirrhosae Bulbus (FCB) is frequently adulterated with its closely related species due to personal or non-man made factors, leading to alterations in the composition of its constituents and compromising the efficacy of its products. Methods: The specific single nucleotide polymorphisms (SNPs) were screened by comparing candidate barcodes of Fritillaria and verified by amplification and sequencing. Herb molecular quantification (Herb-Q) was established by detecting specific SNPs, and the methodological validation was performed. Quantitative standard curves were established for FCB mixed with each adulterated species, and the quantitative validity of this method was verified based on external standard substance. In addition, eight commercial Shedan Chuanbei capsules (SDCBs) randomly selected were detected. Results: FCB and its five adulterants can be distinguished based on the ITS 341 site. The methodological investigation of Herb-Q shows optimal accuracy, and repeatability, which exhibited good linearity with an R2 of 0.9997 (> 0.99). An average bias in quantitative validity was 5.973% between the measured and actual values. Four of eight commercial SDCBs were adulterated with F. ussuriensis or F. thunbergia with adulteration levels ranging from 9 to 15% of the total weight. Conclusion: This study confirmed that Herb-Q can quantitatively detect both the mixed herbs and Chinese patent medicines (CPMs) containing FCB with high reproducibility and accuracy. This method provides technical support for market regulation and helps safeguard patient rights. [ABSTRACT FROM AUTHOR]

Background: As a biological marker for cellular senescence, telomere length (TL) has been linked to a variety of psychiatric disorders and adverse childhood experiences (ACE), though only preliminarily to peripartum depression (PPD). The present study sought to examine the association between TL and PPD, assessing the moderating role of ACE and genetic polymorphic variations related with the telomere machinery. Methods: Adversity was self-reported, likewise were depressive symptoms evaluated at pregnancy week 17 and 32, as well as six-weeks and six-months postpartum. TL was assessed by use of qPCR in blood samples collected during delivery from females with antenatal depression resolving postpartum, females with depression persisting to postpartum, and healthy controls. Twenty haplotype-tagging Single Nucleotide Polymorphisms in the Telomerase Reverse Transcriptase (TERT) and three in the Telomerase RNA Component (TERC) genes were genotyped. Results: TL was negatively correlated with severity of PPD symptoms at pregnancy week 32 and postpartum week 6. PPD was associated with shorter TL. Lastly, ACE, but not the TERT/TERC genotype, moderated the TL-trajectory association; with increasing ACE, individuals with persistent PPD symptoms had shorter TL, whereas the opposite pattern (longer TL) was observed in the controls. Conclusions: The findings contribute to further understanding of PPD underpinnings, suggesting a negative relationship with TL. [ABSTRACT FROM AUTHOR]

Background: Plant mutagenesis creates novel alleles, thereby increasing genetic and phenotypic diversity. The availability of the faba bean (Vicia faba L.) reference genome and a growing set of additional genomic resources has increased the scientific and practical value of mutant collections. We aimed to genotype and morphologically phenotype a historical faba bean mutant collection developed and characterized by Jan Sjödin (1934–2023) over half a century ago in order to increase its value to researchers. The collection was genotyped using high-throughput single-primer enrichment technology (SPET) assays. Results: We used 11,073 informative single nucleotide polymorphism (SNP) markers spanning the faba bean genome to genotype 52 mutant lines along with the background line, cv. Primus. A range of flower, seed, leaf, and stipule mutations were observed. The analysis of population structure revealed a shallow structure with no major subpopulations. Principal component and cluster analyses revealed, to a minor extent, that the mutants clustered by their phenotype. Conclusions: The mutants' phenotypic variation and shallow structure indicate that the Sjödin faba bean collection has the potential to play a significant role in faba bean breeding and in genetic and functional studies. [ABSTRACT FROM AUTHOR]

Background: By 2045, it is expected that 693 million individuals worldwide will have diabetes and with greater risk of morbidity, mortality, loss of vision, renal failure, and a decreased quality of life due to the devastating effects of macro- and microvascular complications. As such, clinical variables and glycemic control alone cannot predict the onset of vascular problems. An increasing body of research points to the importance of genetic predisposition in the onset of both diabetes and diabetic vascular complications. Objectives: Purpose of this article is to review these approaches and narrow down genetic findings for Diabetic Mellitus and its consequences, highlighting the gaps in the literature necessary to further genomic discovery. Material and methods: In the past, studies looking for genetic risk factors for diabetes complications relied on methods such as candidate gene studies, which were rife with false positives, and underpowered genome-wide association studies, which were constrained by small sample sizes. Results: The number of genetic findings for diabetes and diabetic complications has over doubled due to the discovery of novel genomics data, including bioinformatics and the aggregation of global cohort studies. Using genetic analysis to determine whether diabetes individuals are at the most risk for developing diabetic vascular complications (DVC) might lead to the development of more accurate early diagnostic biomarkers and the customization of care plans. Conclusions: A newer method that uses extensive evaluation of single nucleotide polymorphisms (SNP) in big datasets is Genome-Wide Association Studies (GWAS). [ABSTRACT FROM AUTHOR]

Background: A Two-sample Mendelian randomization (MR) Analysis was used to assess the causal relationship between non-small cell lung cancer (NSCLC) and sepsis. Method: Single nucleotide polymorphisms (SNPs) closely associated with NSCLC were utilized as instrumental variables (IVs) in this study. The Inverse Variance Weighted (IVW) method was used as the primary method for MR analysis, supplemented by the Weighted median, Weighted model, and MR-Egger regression method. Sensitivity analysis was conducted to improve result robustness, and data from various sources were validated and integrated. Bonferroni tests were applied to adjust for multiple comparisons. Results: After Bonferroni tests correcting the combined results, MR analysis revealed a significant association between genetically predicted NSCLC and an increased susceptibility to sepsis (odds ratios [OR]: 1.140, 95% confidence interval [CI]: 1.085–1.199, P = 2.61 × 10− 7). The combined results demonstrated that NSCLC is associated with a heightened risk of sepsis in patients under 75 years of age (OR: 1.085, 95%CI: 1.037–1.353, P = 3.84 × 10− 4). Furthermore, lung adenocarcinoma (LUAD) was found to be potentially associated with an increased susceptibility to sepsis (OR: 1.040, 95% CI: 1.009–1.073, P = 1.16 × 10− 2). These results withstood multiple sensitivity analyses, demonstrating their robustness. Conclusion: This study confirms that NSCLC can significantly increase susceptibility to sepsis at the genetic level, providing valuable insights for the early identification of individuals at risk for sepsis. [ABSTRACT FROM AUTHOR]

Background: The genetic basis underlying spawning abilities in the Pacific white shrimp, Penaeus vannamei, remains largely unexplored. To investigate genetic variations potentially related to reproductive performance, a systematic bioinformatic analysis was conducted to identify structural variations (SVs) with different polymorphic spectra in P. vannamei with high fertility (HF) and low fertility (LF). Results: A total of 2,323 and 1,859 SV events were identified exclusively in the HF and LF groups, respectively. These SVs were mapped to 277 genes in the HF group and 231 genes in the LF group. Gene Ontology (GO) enrichment analysis based on SNPs (single nucleotide polymorphism) and SVs revealed several neural-related processes, suggesting the importance of neural regulation in reproduction. Notably, we identified a set of promising genes, including Cttn, Spast, Ppp4c, Spire1, Lhcgr, and Ftz-f1, which may enhance fertility in shrimp. Conclusion: In conclusion, this study is the first to establish a link between SVs and reproductive traits in P. vannamei. The promising genes discovered have the potential to serve as crucial markers for enhancing reproductive traits through targeted genotyping. [ABSTRACT FROM AUTHOR]