Real-time analgesic efficacy and factors determining drug requirements of combined spinal-epidural analgesia for labor: a prospective cohort study.

PURPOSE: Combined spinal-epidural analgesia (CSEA) is effective but not sufficient for labor pain. This study was conducted to assess the real-time analgesic efficacy, side effects of anesthetic drug dosage, and maternal satisfaction in labor to provide reference for the optimization of labor analgesia. METHODS: This was a prospective, cohort, single-center study that included 3020 women who received CSEA for labor analgesia. The visual analogue scale (VAS) for labor pain, real-time anesthetic drug dosage, side effects, adverse labor outcomes, factors influencing average drug dosage, and maternal satisfaction with CSEA were assessed. RESULTS: Overall, the VAS labor pain score was lowest at the first hour after the anesthesia was given. After 4 h for primiparas and 3 h for multiparas, the VAS score was greater than 3 but the anesthetic drug dosage did not reach the maximum allowed dosage at the same time. The average anesthetic drug dosage was positively correlated with fever, urinary retention, uterine atony, prolonged active phase, prolonged second stage, assisted vaginal delivery, and postpartum hemorrhage. The average anesthetic drug dosage was the highest in women ≤ 20 years old, those with a body mass index (BMI) ≥ 24.9 kg/m2, and those with a primary or secondary education level. CONCLUSION: Appropriate age guidance and emphasis on education of labor analgesia, weight management during pregnancy, and real-time anesthetic dosage adjustment during labor based on VAS pain score may have positive effects on the satisfaction of labor analgesia. CLINICAL TRIAL NUMBER AND REGISTRY: Clinicaltrials.gov (ChiCTR2100051809).

B3galt5 functions as a PXR target gene and regulates obesity and insulin resistance by maintaining intestinal integrity.

Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of ß-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.

Molecular characteristics and immune microenvironment of gastrointestinal stromal tumours: targets for therapeutic strategies.

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours, arising mainly from the interstitial cells of Cajal (ICCs) of the gastrointestinal tract. As radiotherapy and chemotherapy are generally ineffective for GISTs, the current primary treatment is surgical resection. However, surgical resection is not choice for most patients. Therefore, new therapeutic strategies are urgently needed. Targeted therapy, represented by tyrosine kinase inhibitors (TKIs), and immunotherapy, represented by immune checkpoint inhibitor therapies and chimeric antigen receptor T-cell immunotherapy (CAR-T), offer new therapeutic options in GISTs and have shown promising treatment responses. In this review, we summarize the molecular classification and immune microenvironment of GISTs and discuss the corresponding targeted therapy and immunotherapy options. This updated knowledge may provide more options for future therapeutic strategies and applications in GISTs.

Identification of core genes in intervertebral disc degeneration using bioinformatics and machine learning algorithms.

Background: Intervertebral Disc Degeneration (IDD) is a major cause of lower back pain and a significant global health issue. However, the specific mechanisms of IDD remain unclear. This study aims to identify key genes and pathways associated with IDD using bioinformatics and machine learning algorithms. Methods: Gene expression profiles, including those from 35 LDH patients and 43 healthy volunteers, were downloaded from the GEO database (GSE124272, GSE150408, GSE23130, GSE153761). After merging four microarray datasets, differentially expressed genes (DEGs) were selected for GO and KEGG pathway enrichment analysis. Weighted Gene Co-expression Network Analysis (WGCNA) was then applied to the merged dataset to identify relevant modules and intersect with DEGs to discover candidate genes with diagnostic value. A LASSO model was established to select appropriate genes, and ROC curves were drawn to elucidate the diagnostic value of genetic markers. A Protein-Protein Interaction (PPI) network was constructed and visualized to determine central genes, followed by external validation using qRT-PCR. Results: Differential analysis of the preprocessed dataset identified 244 genes, including 183 upregulated and 61 downregulated genes. WGCNA analysis revealed the most relevant module intersecting with DEGs, yielding 9 candidate genes. The lasso-cox method was used for regression analysis, ultimately identifying 6 genes: ASPH, CDC42EP3, FOSL2, IL1R1, NFKBIZ, TCF7L2. A Protein-Protein Interaction (PPI) network created with GENEMANIA identified IL1R1 and TCF7L2 as central genes. Conclusion: Our study shows that IL1R1 and TCF7L2 are the core genes of IDD, offering new insights into the pathogenesis and therapeutic development of IDD.

Hybridizing Shear-Stiffening Gel and Chemically-Strengthened Ultrathin Glass Sheets for Flexible Impact-Resistant Armor.

Traditional anti-impact armors and shields are normally made of stiff and hard materials and therefore deficient in flexibility. This greatly limits their applications in protecting objects with complex geometries or significant deformability. Flexible armors can be developed with the application of hard platelets and soft materials, but the lower rigidity of the flexible armors renders them incapable of providing sufficient resistance against impact attacks. To address the inherent conflict between flexibility and impact resistance in traditional armors, here, a composite is developed by hybridizing a shear-stiffening gel as the matrix and chemically-strengthened ultrathin glass sheets (CSGS) as the reinforcement. The resulting laminate, termed PCCL, exhibits both high flexibility and high impact resistance. Specifically, at low strain rates, the high ductility of the gel combined with the high flexural strength of the CSGS enables the PCCL to undergo considerable deformation; at high strain rates, on the other hand, the shear stiffening behavior of the gel matrix endows the PCCL with excellent impact resistance manifested by its high performance in energy absorption and high rigidity. With the combination of high flexibility and high impact resistance, the PCCL is demonstrated to be an ideal armor for protecting curved vulnerable objects from impact attacks.

Whole-genome sequencing reveals genomic diversity and selection signatures in Xia'nan cattle.

BACKGROUND: The crossbreeding of specialized beef cattle breeds with Chinese indigenous cattle is a common method of genetic improvement. Xia'nan cattle, a crossbreed of Charolais and Nanyang cattle, is China's first specialized beef cattle breed with independent intellectual property rights. After more than two decades of selective breeding, Xia'nan cattle exhibit a robust physique, good environmental adaptability, good tolerance to coarse feed, and high meat production rates. This study analyzed the population genetic structure, genetic diversity, and genomic variations of Xia'nan cattle using whole-genome sequencing data from 30 Xia'nan cattle and 178 published cattle genomic data. RESULT: The ancestry estimating composition analysis showed that the ancestry proportions for Xia'nan cattle were mainly Charolais with a small amount of Nanyang cattle. Through the genetic diversity studies (nucleotide diversity and linkage disequilibrium decay), we found that the genomic diversity of Xia'nan cattle is higher than that of specialized beef cattle breeds in Europe but lower than that of Chinese native cattle. Then, we used four methods to detect genome candidate regions influencing the excellent traits of Xia'nan cattle. Among the detected results, 42 genes (θπ and CLR) and 131 genes (FST and XP-EHH) were detected by two different detection strategies. In addition, we found a region in BTA8 with strong selection signals. Finally, we conducted functional annotation on the detected genes and found that these genes may influence body development (NR6A1), meat quality traits (MCCC1), growth traits (WSCD1, TMEM68, MFN1, NCKAP5), and immunity (IL11RA, CNTFR, CCL27, SLAMF1, SLAMF7, NAA35, and GOLM1). CONCLUSION: We elucidated the genomic features and population structure of Xia'nan cattle and detected some selection signals in genomic regions potentially associated with crucial economic traits in Xia'nan cattle. This research provided a basis for further breeding improvements in Xia'nan cattle and served as a reference for genetic enhancements in other crossbreed cattle.

Single-cell analysis of ovarian myeloid cells identifies aging associated changes in macrophages and signaling dynamics.

The aging of mammalian ovary is accompanied by an increase in tissue fibrosis and heightened inflammation. Myeloid cells, including macrophages, monocytes, dendritic cells, and neutrophils, play pivotal roles in shaping the ovarian tissue microenvironment and regulating inflammatory responses. However, a comprehensive understanding of the roles of these cells in the ovarian aging process is lacking. To bridge this knowledge gap, we utilized single-cell RNA sequencing (scRNAseq) and flow cytometry analysis to functionally characterize CD45+ CD11b+ myeloid cell populations in young (3 months old) and aged (14-17 months old) murine ovaries. Our dataset unveiled the presence of five ovarian macrophage subsets, including a Cx3cr1 low Cd81 hi subset unique to the aged murine ovary. Most notably, our data revealed significant alterations in ANNEXIN and TGFß signaling within aged ovarian myeloid cells, which suggest a novel mechanism contributing to the onset and progression of aging-associated inflammation and fibrosis in the ovarian tissue.

Metabolically active neutrophils represent a permissive niche for Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb)-infected neutrophils are often found in the airways of patients with active tuberculosis (TB), and excessive recruitment of neutrophils to the lung is linked to increased bacterial burden and aggravated pathology in TB. The basis for the permissiveness of neutrophils for Mtb and the ability to be pathogenic in TB has been elusive. Here, we identified metabolic and functional features of neutrophils that contribute to their permissiveness in Mtb infection. Using single-cell metabolic and transcriptional analyses, we found that neutrophils in the Mtb-infected lung displayed elevated mitochondrial metabolism, which was largely attributed to the induction of activated neutrophils with enhanced metabolic activities. The activated neutrophil subpopulation was also identified in the lung granulomas from Mtb-infected non-human primates. Functionally, activated neutrophils harbored more viable bacteria and displayed enhanced lipid uptake and accumulation. Surprisingly, we found that interferon-γ promoted the activation of lung neutrophils during Mtb infection. Lastly, perturbation of lipid uptake pathways selectively compromised Mtb survival in activated neutrophils. These findings suggest that neutrophil heterogeneity and metabolic diversity are key to their permissiveness for Mtb and that metabolic pathways in neutrophils represent potential host-directed therapeutics in TB.

Conjugation through Si-O-Si bonds, silsesquioxane (SQ) half cage copolymers, extended examples via SiO0.5/SiO1.5 units: multiple emissive states in violation of Kasha's rule.

We previously reported that phenyl- and vinyl-silsesquioxanes (SQs), [RSiO1.5]8,10,12 (R = Ph or vinyl) functionalized with three or more conjugated moieties show red-shifted absorption- and emission features suggesting 3-D conjugation via a cage centered LUMOs. Corner missing [PhSiO1.5]7(OSiMe3)3 and edge opened, end capped [PhSiO1.5]8(OSiMe2)2 (double decker, DD) analogs also offer red shifted spectra again indicating 3-D conjugation and a cage centered LUMO. Copolymerization of DD [PhSiO1.5]8(OSiMevinyl)2 with multiple R-Ar-Br gives copolymers with emission red-shifts that change with degree of polymerization (DP), exhibit charge transfer to F4TNCQ and terpolymer averaged red-shifts suggesting through chain conjugation even with two (O-Si-O) end caps possibly via a cage centered LUMO. Surprisingly, ladder (LL) SQ, (vinylMeSiO2)[PhSiO1.5]4(O2SiMevinyl) copolymers offer emission red-shifts even greater for analogous copolymers requiring a different explanation. Here we assess the photophysical behavior of copolymers of a more extreme SQ form: the half cage [PhSiO1.5]4(OSiMe2Vinyl)4, Vy4HC SQs. We again see small red-shifted absorptions coupled with significant red-shifted emissions, even with just a half cage, thus further supporting the existence of pπ-dπ and/or σ*-π* conjugation through Si-O-Si bonds and contrary to most traditional views of Si-O-Si linked polymers. These same copolymers donate an electron to F4TCNQ generating the radical anion, F4TCNQ-. as further proof of conjugation. Column chromatographic separation of short from longer chain oligomers reveals a direct correlation between DP and emission λmax red-shifts as another indication of conjugation. Further, one- and two-photon absorption and emission spectroscopy reveals multiple excited fluorescence-emitting states in a violation of Kasha's rule wherein emission occurs only from the lowest excited state. Traditional modeling studies again find HOMO LUMO energy levels residing only on the aromatic co-monomers rather than through Si-O-Si bonds as recently found in related polymers.

Risk factors analysis and multidisciplinary team first-aid simulation training for umbilical cord prolapse can improve neonatal outcomes.

OBJECTIVE: In the present study, we sought to identify risk factors for umbilical cord prolapse (UCP) and adapt the multidisciplinary team (MDT) first-aid simulation training for UCP patients. We evaluated the usefulness of the MDT first-aid simulation by comparing delivery outcomes for UCP patients before and after its implementation. MATERIAL AND METHODS: A retrospective review was conducted on 149 UCP cases (48 overt and 101 occult) and 298 control deliveries that occurred at the Third Affiliated Hospital of Sun Yat-sen University from January 1998 to December 2022. Patient data were compared between the groups. One-way analysis of variance (ANOVA) was used for means comparison, and the chi-square test was used for categorical data. Univariate and multivariate logistic regression analyses were performed to identify factors significantly associated with UCP. RESULTS: Overt UCP was strongly associated with all adverse delivery outcomes. Both univariate and multivariate analyses identified multiparity, breech presentation, polyhydramnios, and low birth weight as independent risk factors for overt UCP (all odds ratios [OR] > 1; all p < 0.05). Preterm labor and abnormal placental cord insertion were identified as independent risk factors for occult UCP (all OR > 1; all p < 0.05). After 2014, when obstetrical staff received MDT first-aid simulation training, patients with overt UCP experienced shorter decision-to-delivery intervals due to more timely cesarean sections. They also had higher Apgar scores at 1, 5, and 10 min, and lower admission rates to the neonatal intensive care unit compared to patients before 2014 (all p < 0.05). CONCLUSION: MDT first-aid simulation training for overt UCP can improve neonatal outcomes. However, medical simulation training efforts should initially focus on the early identification of risk factors for both overt and occult UCP.

Overt umbilical cord prolapse (UCP) is an obstetric emergency that can lead to adverse delivery outcomes. Early identification of risk factors for both overt and occult UCP is beneficial for facilitating early interventions. Multidisciplinary team first-aid simulation training specifically for overt UCP has been shown to effectively improve neonatal outcomes.

POLB Regulates Proliferation and Apoptosis of Bovine Primary Myocytes.

DNA polymerase ß (DNA polymerase beta (POLB)) belongs to a member of the DNA polymerase X family, mainly involved in various biological metabolic processes, such as eukaryotic DNA replication, DNA damage repair, gene recombination, and cell cycle regulation. In this study, the muscle development-related gene POLB was screened by selection signature and RNA-seq analysis and then validated for the proliferation and apoptosis of bovine primary myocytes. It was also found that overexpression of the POLB gene had a pro-apoptosis effect, but interfering with the expression of the gene had no significant effect on cells. Then, the analysis of related apoptotic genes revealed that POLB overexpression affected CASP9 gene expression.

Reactive Oxygen Species-Responsive Delivery of a Notch Inhibitor to Alleviate Nonalcoholic Steatohepatitis by Inhibiting Hepatic de Novo Lipogenesis and Inflammation.

With the increased prevalence of nonalcoholic steatohepatitis (NASH) in the world, effective pharmacotherapy in clinical practice is still lacking. Previous studies have shown that dibenzazepine (DBZ), a Notch inhibitor, could alleviate NASH development in a mouse model. However, low bioavailability, poor water solubility, and extrahepatic side effects restrict its clinical application. To overcome these barriers, we developed a reactive oxygen species (ROS)-sensitive nanoparticle based on the conjugation of bilirubin to poly(ethylene glycol) (PEG) chains, taking into account the overaccumulation of hepatic ROS in the pathologic state of nonalcoholic steatohepatitis (NASH). The PEGylated bilirubin can self-assemble into nanoparticles in an aqueous solution and encapsulate insoluble DBZ into its hydrophobic cavity. DBZ nanoparticles (DBZ Nps) had good stability, rapidly released DBZ in response to H2O2, and effectively scavenged intracellular ROS of hepatocytes. After systemic administration, DBZ Nps could accumulate in the liver of the NASH mice, extend persistence in circulation, and improve the bioavailability of DBZ. Furthermore, DBZ Nps significantly improved glucose intolerance, relieved hepatic lipid accumulation and inflammation, and ameliorated NASH-induced liver fibrosis. Additionally, DBZ Nps had no significant extrahepatic side effects. Taken together, our results highlight the potential of the ROS-sensitive DBZ nanoparticle as a promising therapeutic strategy for NASH.

Antibiotic exposure alters the honeybee gut microbiota and may interfere with the honeybee behavioral caste transition.

Behavioral division is essential for the sustainability and reproduction of honeybee populations. While accumulating evidence has documented that antibiotic exposure interferes with bee behavioral divisions, how the gut microbiome, host physiology, and genetic regulation are implicated in this process remains understudied. Here, by constructing single-cohort colonies, we validated that the gut microbiota varied in composition between age-matched nurse and forager bees. Perturbing the gut microbiota with a low dose of antibiotic retained the gut bacterial size, but the structure of the microbial community continuously diverged from the control group after antibiotic treatment. Fewer foragers were observed in the antibiotic groups in the field experiment. A combinatorial effect of decreased gut metabolic gene repertoires, reduced brain neurotransmitter titers, and downregulated brain immune genes could potentially be related to behavioral tasks transition delay. This work indicates that the disturbance to both the gut microbiome and host physiologies after antibiotic exposure may have implications on social behavior development, highlighting the need for further research focusing on antibiotic pollution threatening the honeybee population's health.

Litchi aspartic protease LcAP1 enhances plant resistance via suppressing cell death triggered by the pectate lyase PlPeL8 from Peronophythora litchii.

Plant cell death is regulated in plant-pathogen interactions. While some aspartic proteases (APs) participate in regulating programmed cell death or defense responses, the defense functions of most APs remain largely unknown. Here, we report on a virulence factor, PlPeL8, which is a pectate lyase found in the hemibiotrophic pathogen Peronophythora litchii. Through in vivo and in vitro assays, we confirmed the interaction between PlPeL8 and LcAP1 from litchi, and identified LcAP1 as a positive regulator of plant immunity. PlPeL8 induced cell death associated with NbSOBIR1 and NbMEK2. The 11 conserved residues of PlPeL8 were essential for inducing cell death and enhancing plant susceptibility. Twenty-three LcAPs suppressed cell death induced by PlPeL8 in Nicotiana benthamiana depending on their interaction with PlPeL8. The N-terminus of LcAP1 was required for inhibiting PlPeL8-triggered cell death and susceptibility. Furthermore, PlPeL8 led to higher susceptibility in NbAPs-silenced N. benthamiana than the GUS-control. Our results indicate the crucial roles of LcAP1 and its homologs in enhancing plant resistance via suppression of cell death triggered by PlPeL8, and LcAP1 represents a promising target for engineering disease resistance. Our study provides new insights into the role of plant cell death in the arms race between plants and hemibiotrophic pathogens.

Iron-catalyzed stereoselective C-H alkylation for simultaneous construction of C-N axial and C-central chirality.

The assembly of chiral molecules with multiple stereogenic elements is challenging, and, despite of indisputable advances, largely limited to toxic, cost-intensive and precious metal catalysts. In sharp contrast, we herein disclose a versatile C-H alkylation using a non-toxic, low-cost iron catalyst for the synthesis of substituted indoles with two chiral elements. The key for achieving excellent diastereo- and enantioselectivity was substitution on a chiral N-heterocyclic carbene ligand providing steric hindrance and extra represented by noncovalent interaction for the concomitant generation of C-N axial chirality and C-stereogenic center. Experimental and computational mechanistic studies have unraveled the origin of the catalytic efficacy and stereoselectivity.

A review on recent taxonomic updates of gut bacteria associated with social bees, with a curated genomic reference database.

Honeybees and bumblebees play a crucial role as essential pollinators. The special gut microbiome of social bees is a key factor in determining the overall fitness and health of the host. Although bees harbor relatively simple microbial communities at the genus level, recent studies have unveiled significant genetic divergence and variations in gene content within each bacterial genus. However, a comprehensive and refined genomics-based taxonomic database specific to social bee gut microbiomes remains lacking. Here, we first provided an overview of the current knowledge on the distribution and function of social bee gut bacteria, as well as the factors that influence the gut population dynamics. We then consolidated all available genomes of the gut bacteria of social bees and refined the species-level taxonomy, by constructing a maximum-likelihood core genome phylogeny and calculating genome-wide pairwise average nucleotide identity. On the basis of the refined species taxonomy, we constructed a curated genomic reference database, named the bee gut microbe genome sequence database (BGM-GDb). To evaluate the species-profiling performance of the curated BGM-GDb, we retrieved a series of bee gut metagenomic data and inferred the species-level composition using metagenomic intra-species diversity analysis system (MIDAS), and then compared the results with those obtained from a prebuilt MIDAS database. We found that compared with the default database, the BGM-GDb excelled in aligned read counts and bacterial richness. Overall, this high-resolution and precise genomic reference database will facilitate research in understanding the gut community structure of social bees.

SARS-CoV-2 Infection Causes Heightened Disease Severity and Mortality in a Mouse Model of Down Syndrome.

Recent epidemiological studies suggest that individuals with Down syndrome are more susceptible to SARS-CoV-2 infection and have higher rates of hospitalization and mortality than the general population. However, the main drivers behind these disparate health outcomes remain unknown. Herein, we performed experimental infections with SARS-CoV-2 in a well-established mouse model of Down syndrome. We observed similar SARS-CoV-2 replication kinetics and dissemination in the primary and secondary organs between mice with and without Down syndrome, suggesting that both groups have similar susceptibilities to SARS-CoV-2 infection. However, Down syndrome mice exhibited more severe disease as defined by clinical features including symptoms, weight loss, pulmonary function, and survival of mice. We found that increased disease severity in Down syndrome mice could not be attributed solely to increased infectivity or a more dramatic pro-inflammatory response to infection. Rather, results from RNA sequencing suggested that differences in the expression of genes from other physiological pathways, such as deficient oxidative phosphorylation, cardiopulmonary dysfunction, and deficient mucociliary clearance in the lungs may also contribute to heightened disease severity and mortality in Down syndrome mice following SARS-CoV-2 infection.

Nickel-Catalyzed Atroposelective C-H Alkylation Enabled by Bimetallic Catalysis with Air-Stable Heteroatom-Substituted Secondary Phosphine Oxide Preligands.

The catalytic asymmetric construction of axially chiral C-N atropisomers remains a formidable challenge due to their low rotational barriers and is largely reliant on toxic, cost-intensive, and precious metal catalysts. In sharp contrast, we herein describe the first nickel-catalyzed atroposelective C-H alkylation for the construction of C-N axially chiral compounds with the aid of a chiral heteroatom-substituted secondary phosphine oxide (HASPO)-ligated Ni-Al bimetallic catalyst. A wide range of alkenes, including terminal and internal alkenes, were well compatible with the reaction, providing a variety of benzimidazole derivatives in high yields and enantioselectivities (up to 97:3 e.r.). The key to success was the identification of novel HASPOs as highly effective chiral preligands. Mechanistic studies revealed the catalyst mode of action, and in-depth data science analysis elucidated the key features of the responsible chiral preligands in controlling the enantioselectivity.

The Identification of Goat KCNJ15 Gene Copy Number Variation and Its Association with Growth Traits.

(1) Background: Copy number variation (CNV) is a critical component of genome structural variation and has garnered significant attention. High-throughput screening of the KCNJ15 gene has revealed a correlation between the CNV region and the growth traits of goats. We aimed to identify the CNV of the KCNJ15 gene in five goat breeds and analyze its association with growth characteristics. (2) Methods: We utilized 706 goats from five breeds: Guizhou black goat (GZB), Guizhou white goat (GZW), Bohuai goat (BH), Huai goat (HH), and Taihang goat (TH). To evaluate the number of copies of the KCNJ15 gene using qPCR, we analyzed the correlation between the CNV and growth characteristics and then used a universal linear model. The findings revealed variations in the distribution of different copy number types among the different goat breeds. (3) Results: Association analysis revealed a positive influence of the CNV in the KCNJ15 gene on goat growth. In GZB, individuals with duplication types exhibited superior performance in terms of cannon bone circumference (p < 0.05). In HH, individuals with duplication types exhibited superior performance in terms of body slanting length (p < 0.05). Conversely, normal TH demonstrated better body height and body weight (p < 0.05), while in GZW, when CN = 3, it performed better than other types in terms of body weight and chest circumference (p < 0.05). However, in BH, it had no significant effect on growth traits. (4) Conclusions: We confirmed that the CNV in the KCNJ15 gene significantly influences the growth characteristics of four distinct goat breeds. The correlation between KCNJ15 gene CNVs and goat growth traits offers valuable insights to breeders, enabling them to employ precise and efficient breeding methods that enhance livestock welfare, productivity, and overall economic benefits in the industry.

HNF4A as a potential target of PFOA and PFOS leading to hepatic steatosis: Integrated molecular docking, molecular dynamic and transcriptomic analyses.

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are indeed among the most well known and extensively studied Per- and polyfluoroalkyl substances (PFASs), and increasing evidence confirm their effects on human health, especially liver steatosis. Nonetheless, the molecular mechanisms of their initiation of hepatic steatosis is still elusive. Therefore, potential targets of PFOA/PFOS must be explored to ameliorate its adverse consequences. This research aims to investigate the molecular mechanisms of PFOA and PFOS-induced liver steatosis, with emphasis on identifying a potential target that links these PFASs to liver steatosis. The potential target that causes PFOA and PFOS-induced liver steatosis have been explored and determined based on molecular docking, molecular dynamics (MD) simulation, and transcriptomics analysis. In silico results show that PFOA/PFOS can form a stable binding conformation with HNF4A, and PFOA/PFOS may interact with HNF4A to affect the downstream conduction mechanism. Transcriptome data from PFOA/PFOS-induced human stem cell spheres showed that HNF4A was inhibited, suggesting that PFOA/PFOS may constrain its function. PFOS mainly down-regulated genes related to cholesterol synthesis while PFOA mainly up-regulated genes related to fatty acid ß-oxidation. This study explored the toxicological mechanism of liver steatosis caused by PFOA/PFOS. These compounds might inhibit and down-regulate HNF4A, which is the molecular initiation events (MIE) that induces liver steatosis.