BACKGROUND AND PURPOSE:Thrombosis, the leading cause of death worldwide, involves both platelet activation and coagulation reaction. Astaxanthin (ASX) is a carotenoid with potent antioxidant activity and beneficial effects to the cardiovascular system. This study aims to systematically elucidate the antithrombotic potential of ASX and the underlying mechanisms. EXPERIMENTAL APPROACH:Rats and mice were treated with ASX by gavage to examine the in vivo effects of ASX. Human platelets and liver cells were directly treated with ASX to evaluate its in vitro effects. Network pharmacology and immunoblotting were performed to analyse the targets of ASX. Thrombus components including platelets and fibrin were visualized by specific fluorescent antibodies using intravital microscopy. KEY RESULTS:ASX treatment led to attenuated platelet aggregation, adhesion, spreading, clot retraction and reduced integrin activation and granule secretion. ASX inhibited reactive oxygen species (ROS) production, and its downstream signalling pathways PI3K/Akt/mTOR and MAPK/ERK during platelet activation. ASX suppressed blood coagulation, both extrinsic and intrinsic, by interfering with hepatic transcription of coagulation factors through reducing hepatic ROS and ROS-responsive hepatocyte nuclear factor 4α (HNF4α). Treatment with ASX in human platelets and liver cells recapitulated the observations in animals. ASX and aspirin comparably inhibited FeCl3-induced arterial thrombosis and stenosis-induced venous thrombosis. However, unlike aspirin which targets only platelets, ASX inhibited both platelets and fibrin in the cremaster thrombosis model without causing excessive bleeding. CONCLUSION AND IMPLICATIONS:ASX exhibits multiple antithrombotic effects by suppressing platelet- and hepatic-ROS and the downstream responsive pathways. ASX represents a novel strategy for thrombosis prevention.

The NS1 protein of influenza A virus (IAV) is a multi-functional protein which can antagonize host immune system and facilitate viral replication by interacting with host factors. However, the novel partners in host cells interacting with NS1 need to be fully elucidated. In the current study, we identified hnRNPH1 as a novel binding partner of NS1 to regulate IAV replication. Notably, overexpression of hnRNPH1 decreased IAV multiplication, while knockdown of hnRNPH1 enhanced IAV replication. hnRNPH1 can interact with NS1 to change the intracellular localization and splicing function of NS1, and impact IAV replication through interacting with p53 to regulate cell apoptosis. In addition, the RBD domain of NS1 and the RRM and NLS regions of hnRNPH1 may be the major sites for their interaction. In summary, our studies identified hnRNPH1 as a novel NS1-binding protein and elucidated its regulatory roles in IAV replication, which will provide new insights into the roles of NS1 binding proteins, and give a reference for anti-IAV therapy based on NS1-host interaction.

Fat volume and obesity-related genes (e.g., the FTO gene) are important candidate genes affecting energy metabolism. Single nucleotide polymorphisms (SNPs) in the FTO gene are associated with carcass, growth and meat quality traits of pigs, cattle, sheep, rabbits and ducks. The purpose of this study was to detect the single nucleotide polymorphisms in the chicken FTO gene coding region by DNA sequencing and analyze its association with the carcass and growth traits of Heying black chickens. We detected polymorphisms in exons 5, 7, 8 and 9, respectively, g.57337C>A, g.64757T>G, g.97213G>A and g.220985G>A, which are synonymous mutations. g.57337C>A mutation site CA and AA genotype individuals were significantly higher than CC genotype individuals in live weights, head weights, breast muscle weights and leg muscle weights (p < 0.05), AA genotype individuals were significantly higher than CC genotype individuals in slaughter live weights and liver weights (p < 0.05) and CA and AA genotype individuals were significantly higher than CC genotype individuals in heart weights (p < 0.01). In terms of growth traits, the weights of individuals with genotype CA at 8 weeks were significantly higher than that of individuals with genotype CC (p < 0.05), and the weights of individuals with genotype AA and CA at 10 weeks and 16 weeks were significantly higher than that of individuals with genotype CC (p < 0.05). For the g.64757T > G mutation, individuals with the TT genotype exhibited significantly higher values (p < 0.05) than those with the TG genotype across multiple traits, including slaughter weight, live weight, eviscerated weight and semi-eviscerated weight. Individuals with GG genotypes were significantly higher than individuals with TG genotypes (p < 0.05) in slaughter weights and wing weights. In terms of growth traits, the 16-week-old body weight of individuals with TT genotype was significantly higher than that of individuals with TG genotype (p < 0.01). The GA genotype exhibited significantly higher slaughter weights in the g.97213G>A variant compared to the GG genotype (p < 0.01), and in live weights, eviscerated weights, semi-eviscerated weights, leg muscle weights and wing weights, GA genotype was significantly higher than in GG genotype (p < 0.05). In terms of growth traits, GA genotype was significantly higher in individuals 8 weeks old, 10 weeks old and 16 weeks old than GG genotype (p < 0.05). g.220985G>A was significantly higher in individuals with GG genotype than GA genotype (p < 0.05). In terms of growth traits, the weight of GG genotype was significantly higher than that of GA genotype (p < 0.05). The results showed that the FTO gene may be a candidate gene related to chicken growth and slaughter traits and lays a foundation for Heying black chicken assisted breeding.

Mastitis is an important disease limiting milk production in dairy cows. Somatic cell score is commonly used as one of the main ways to gauge the level of mastitis in dairy cows, with higher somatic cell scores usually indicating possible mastitis. However, the main molecular markers affecting somatic cell scores remain unknown. The aim of this study was to investigate the association between single nucleotide polymorphisms in the SLC11A1 gene and somatic cell score in Chinese Holstein cows. In this study, 210 Chinese Holstein cows were genotyped and potential SNPs were detected by DNA sequencing, PCR-SSCP and PCR-RFLP analysis. Our results revealed two SNPs were identified in the CDS region of SLC11A1: c.723C>T and c.1144C>G. For the c.723C>T polymorphic site, two genotypes (AA, AB) were found and the genotype frequencies were 0.790 and 0.210, respectively. The results of the association analysis showed that the mean somatic cell score of the AA genotypes were significantly lower than those of the AB genotypes, suggesting that the A allele is a potential marker for improving mastitis resistance in Chinese Holstein cows. For the c.1144C>G polymorphic site, three genotypes (CC, CD, and DD) were found and the genotype frequencies were 0.629, 0.352 and 0.019, respectively. The association analysis revealed that the mean somatic cell score of CC genotypes was lower than that of CD and DD genotypes, however, no significant differences were observed among the various genotype groups when subjected to pair-wise comparisons. The bioinformatic analysis showed that these mutations affected the secondary and tertiary structure of SLC11A1 mRNA, suggesting that they may affect gene expression or protein translation and function. Finally, we predicted the SLC11A1 protein interaction network and found that SPI1, NOD2, TLR2 and S100A12 interacted with SLC11A1 and were reported as candidate genes associated with mastitis resistance. The results indicated that the SNP (c.723C>T) could be potential molecular marker for improving mastitis resistance traits in Chinese Holstein cows. We recommend further validation of this SNP in larger populations and its potential integration into breeding programs to enhance mastitis resistance in dairy cows.

Brucellosis is classified as a class II animal disease in China, with recent years seeing an increasing prevalence of Brucella infections in livestock, posing a significant threat to public health. In this study, a novel IFN-γ enzyme-linked immunospot (ELISpot; Brucella purified protein derivative, Br-PPD) assay specifically tailored for detecting Brucella-infected cattle and goats was developed. This assay employed bovine and goat IFN-γ monoclonal antibodies, 3E3 and biotinylated 8D3, respectively, for capturing and detecting IFN-γ. This method demonstrated high sensitivity and specificity. When 10 spot-forming units was selected as the cut-off value, the sensitivity and specificity of the method were 96.9% and 90.6%, respectively. Compared with the ELISA method, the IFN-γ ELISpot assay showed ∼30 times greater sensitivity in detecting IFN-γ release from peripheral blood mononuclear cells. When applied to clinical samples from both cattle and goats, the ELISpot results strongly correlated with traditional antibody-based diagnostic methods, including the serum agglutination test (SAT), rose bengal plate test (RBPT), and competitive ELISA. The positive agreement rate exceeded 80%, and the negative agreement rate surpassed 90%. Notably, employing Brucella-vaccinated goat models, our study has confirmed that the ELISpot assay can detect Brucella infections earlier than the SAT and offers a more extended diagnostic window. As a cellular immunology-based diagnostic tool, the IFN-γ ELISpot (Br-PPD) assay holds considerable potential to improve early detection of Brucella-infected cattle and goats, addressing existing diagnostic shortcomings.

Background and aims. Undernutrition coexists with tuberculosis and is associated with adverse treatment outcomes. Nutrition packages have been incorporated into tuberculosis patient care in some regions but there are little data on its effectiveness. The aim of this study is to evaluate the effect of a nutrition package on the treatment response and nutritional status of tuberculosis patients. Methods. We conducted a double-blinded placebo-controlled randomized trial in 360 pulmonary tuberculosis patients with concurrent diabetes or prediabetes. The participants were randomly assigned to receive a daily nutrition package (112 kcal, 9 g protein, and micronutrients) or a daily placebo package (112 kcal, 3 g protein, and no micronutrients) during tuberculosis treatment. The intervention lasted for six months. All participants received standard pulmonary tuberculosis treatment. The clinical symptoms, sputum smear, chest computed tomography, and nutritional status were monitored during the intervention. Results. The nutrition package improved the expectoration (intervention vs. placebo: 34.1% vs. 48.3% in week 1, 27.8% vs. 45.0% in week 2, 25.9% vs. 38.6% in week 3, 25.6% vs. 35.4% in month 1, 15.3% vs. 22.9% in month 2) and chest pain (2.3% vs. 9.0% in week 3, 3.6% vs. 8.3% in month 1, 4.3% vs. 10.0% in month 2, 1.8% vs. 6.4% in month 4). The nutrition package also increased hemoglobin, albumin, and lymphocyte counts. The nutrition package did not influence the sputum smear conversion in the whole population [hazard ratio (95% CI): 1.031 (0.685, 1.550), P = 0.885], but accelerated the conversion in patients without cavity [2.583 (1.180, 5.656), P = 0.018]. Conclusions. The nutrition package improved the clinical symptoms (e.g. chest pain and expectoration) and alleviated undernutrition (e.g. anemia and hypoproteinemia) among tuberculosis patients. The study was registered at the China Clinical Trial Registry Center (no. ChiCTR1900022294; https://www.chictr.org.cn).

Background: Evidence links major depressive disorder (MDD) with aging, but it's unclear if MDD accelerates aging and what factors mediate this transition. Methods: Two-sample Mendelian randomization (MR) analyses were applied to estimate the causal association between MDD and frailty index (FI), telomere length (TL), and appendicular lean mass (ALM) from available genome-wide association studies in populations of European ancestry. Furthermore, we conducted mediation MR analyses to assess the mediating effects of 31 lifestyle factors or diseases on the causal relationship between MDD and aging. Results: MDD was significantly causally associated with increased FI (8IVW = 0.23, 95 % CI = 0.18 to 0.28, p = 1.20 x 10-17), shorter TL (8IVW = -0.04, 95 % CI = -0.07 to -0.01, p = 0.01), and decreased ALM (8IVW = -0.07, 95 % CI = -0.11 to -0.03, p = 3.54 x 10-4). The mediation analysis through two-step MR revealed smoking initiation (9.09 %), hypertension (6.67 %) and heart failure (5.36 %) mediated the causal effect of MDD on FI. Additionally, alcohol use disorders and alcohol dependence on the causal relationship between MDD and TL were found to be 17.52 % and 17.13 % respectively. Limitations: Confounding, statistical power, and Euro-centric focus limit generalization. Conclusion: Overall, individuals with MDD may be at a higher risk of experiencing premature aging, and this risk is partially influenced by the pathways involving smoking, alcohol use, and cardiovascular health. It underscores the importance of early intervention and comprehensive health management in individuals with MDD to promote healthy aging and overall well-being.

Radiotherapy is the conventional treatment for pelvic abdominal tumors. However, it can cause some damage to the small intestine and colorectal, which are very sensitive to radiation. Radiation-induced intestinal injury (RIII) affects the prognosis of radiotherapy, causing sequelae of loss of function and long-term damage to patients’ quality of life. Swertiamarin is a glycoside that has been reported to prevent a variety of diseases including but not limited to diabetes, hypertension, atherosclerosis, arthritis, malaria, and abdominal ulcers. However, its therapeutic effect and mechanism of action on RIII have not been established. We investigated whether swertiamarin has a protective effect against RIII. In this article, we use irradiator to create cellular and mouse models of radiation damage. Preventive administration of swertiamarin could reduce ROS and superoxide anion levels to mitigate the cellular damage caused by radiation. Swertiamarin also attenuated RIII in mice, as evidenced by longer survival, less weight loss and more complete intestinal barrier. We also found an increase in the relative abundance of primary bile acids in irradiated mice, which was reduced by both FXR agonists and swertiamarin, and a reduction in downstream interferon and inflammatory factors via the cGAS-STING pathway to reduce radiation-induced damage.

Background and purposeNutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury.MethodsThis cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA).ResultsThe CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40–0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35–0.64)] in the multivariate logistic model. A positive association between “Organ meat, poultry, and vegetable oil” dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42–6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09–3.05)] was observed.ConclusionIn conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the “Organ meat, poultry, and vegetable oil” dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.

AbstractHyperglycemia is prevalent and closely associated with pulmonary tuberculosis (PTB). This study aimed to investigate the effects of hyperglycemia on the outcomes of PTB treatment. This study comprised 791 patients with PTB in total. Patients with fasting plasma glucose levels of ≥ 6.1 mmol/L were diagnosed with hyperglycemia. Anthropometric and baseline demographic data were also collected. The treatment response was assessed based on clinical symptoms (sputum production, cough, chest pain, fever, hemoptysis, night sweats, loss of appetite, and fatigue), sputum smear, chest computed tomography (CT), and adverse gastrointestinal responses (vomiting, nausea, abdominal distension, diarrhea, and constipation). A generalized estimating equation (GEE) was used to evaluate these relationships. Hyperglycemia affected 266 (33.6%) of the 791 patients with PTB. In GEE analyses, patients with hyperglycemia exhibited a greater incidence of elevated tuberculosis (TB) scores (odds ratio (OR) 1.569; 95% CI 1.040–2.369), cough (OR 1.332; 95% CI 1.050–1.690), and night sweats (OR 1.694; 95% CI 1.288–2.335). Hyperglycemia was linked with a higher risk of positive sputum smears (OR 1.941; 95% CI 1.382–2.727). During therapy, hyperglycemia was also associated with an increased incidence of vomiting (OR 2.738; 95% CI 1.041–7.198), abdominal distension (OR 2.230; 95% CI 1.193–4.171), and constipation (OR 2.372; 95% CI 1.442–3.902). However, the CT results indicated that hyperglycemia did not affect pulmonary lesions in patients with TB. Patients with TB and hyperglycemia are at a higher risk of severe clinical manifestations, positive sputum smears, and adverse gastrointestinal effects and, therefore, the special situation of hyperglycemic patients should be considered in the prevention and treatment of TB.

Abstract Objective The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). Methods Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. Results At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). Conclusions The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.

Plasmid-mediated quinolone resistance (PMQR) genes and mobile colistin resistance (MCR) genes in Escherichia coli (E. coli) have been widely identified, which is considered a global threat to public health. In the present study, we conducted an analysis of MCR genes (mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5) and PMQR genes [qnrA, qnrB, qnrC, qnrD, qnrE1, qnrVC, qnrS, aac(6')-Ib-cr, qepA, and oqxAB] in E. coli from China, 1993-2019. From the 3,663 E. coli isolates examined, 1,613 (44.0%) tested positive for PMQR genes, either individually or in combination. Meanwhile, 262 isolates (7.0%) carried the MCR genes. Minimum inhibitory concentration (MIC) analyses of 17 antibiotics for the MCR gene-carrying strains revealed universal multidrug resistance. Resistance to polymyxin varied between 4 μg/mL and 64 μg/mL, with MIC50 and MIC90 at 8 μg/mL and 16 μg/mL, respectively. In addition, fluctuations in the detection rates of these resistant genes correlated with the introduction of antibiotic policies, host origin, temporal trends, and geographical distribution. Continuous surveillance of PMQR and MCR variants in bacteria is required to implement control and prevention strategies.

Plasmid-mediated quinolone resistance (PMQR) genes and mobile colistin resistance (MCR) genes in Escherichia coli ( E. coli ) have shown an increasing prevalence in recent years. This rise is particularly notable in China and several Southeast Asian countries, representing a significant threat to public health. In the present study, we conducted a retrospective analysis of MCR genes ( mcr-1 , mcr-2 , mcr-3 , mcr-4 , and mcr-5 ) and PMQR genes ( qnrA , qnrB , qnrC , qnrD , qnrE1 , qnrVC , qnrS , aac(6’)-Ib-cr , qepA , and oqxAB ). From the 3,663 E. coli isolates examined, 1,613 (44.0%) tested positive for PMQR genes, either individually or in combination. Meanwhile, 262 isolates (7.0%) carried MCR genes. Minimum inhibitory concentration (MIC) analyses of 17 antibiotics for the MCR gene-carrying strains revealed universal multidrug resistance. Resistance to polymyxin varied between 4 μg/mL and 64 μg/mL, with MIC50 and MIC90 values at 8 μg/mL and 16 μg/mL, respectively. Additionally, fluctuations in the detection rates of these resistant genes correlated with the introduction of antibiotic policies, host origin, temporal trends, and geographical distribution.IMPORTANCE Antimicrobial resistance (AMR) has emerged as a threat to global health and development, and E. coli resistance remains an ongoing clinical challenge. However, the efficacy of colistin and quinolones has been compromised by the presence of various MCR and PMQR genes. To elucidate the prevalence and distribution of MCR and PMQR genes in E. coli isolates, we analyzed 3,663 E. coli isolates from 29 provinces in China from 1993 to 2019. The results show that 1,613 (44.0%) tested positive for PMQR genes, 262 isolates (7.0%) carried MCR genes. And MICs analyses of 17 antibiotics for the MCR gene-carrying strains revealed universal multidrug resistance. These indicated prohibiting or strictly curtailing antimicrobial use in animal or human is urgently needed to reduce the growing threat from AMR.

Liver injury is a main adverse effect of first-line tuberculosis drugs. Current management of tuberculosis-drug-induced liver injury (TBLI) mainly relies on withdrawing tuberculosis drugs when necessary. No effective treatment exists. Various nutrients and functional food ingredients may play a protective role in TBLI. However, a comprehensive review has not been conducted to compare the effects of these nutrients and functional food ingredients. We searched Pubmed and Web of Science databases from the earliest date of the database to March 2023. All available in-vitro , animal and clinical studies that examined the effects of nutritional intervention on TBLI were included. The underlying mechanism was briefly reviewed. Folic acid, quercetin, curcumin, Lactobacillus casei , spirulina and Moringa oleifera possessed moderate evidence to have a beneficial effect on alleviating TBLI mostly based on animal studies. The evidence of other nutritional interventions on TBLI was weak. Alleviating oxidative stress and apoptosis were the leading mechanisms for the beneficial effects of nutritional intervention on TBLI. In conclusion, a few nutritional interventions are promising for alleviating TBLI including folic acid, quercetin, curcumin, L. casei , spirulina and M. oleifera , the effectiveness and safety of which need further confirmation by well-designed randomized controlled trials. The mechanisms for the protective role of these nutritional interventions on TBLI warrant further study, particularly by establishing the animal model of TBLI using the tuberculosis drugs separately.

Observational study indicated that folic acid (FA) supplementation may protect against tuberculosis-drug-induced liver injury (TBLI). The aim is to investigate the effect and mechanism of FA on TBLI in rats. Liver injury was induced by a daily gavage of isoniazid (INH) and rifampicin (RIF) in the model and FA groups. Rats in the FA group were also treated with 2.5 mg/kg body weight FA. Rats in the control group were not treated. Eight rats were used in each group. The severity of liver injury was measured by the serum levels of hepatic enzymes and histological score. The metabolites in serum and liver tissues were analyzed by HPLC-Q-TOF-MS/MS. FA treatment significantly reduced alanine aminotransferase and liver necrosis. Seventy-nine differential metabolites in the serum and liver tissues were identified among the three groups. N-acylethanolamines, INH and RIF metabolites, phosphatidylcholines, lysophosphatidylcholines, monoglycerides, diglycerides and bile acids were regulated by FA treatment, involving key metabolic pathways, such as N-acylethanolamine metabolism, INH and RIF metabolism, liver regeneration, inflammation alleviation and bile acid metabolism. RT-PCR and western blotting results confirmed the altered N-acylethanolamine metabolism and improved drug metabolism by FA. In conclusion, FA was protective against TBLI, which may be related to the regulation of N-acylethanolamine metabolism and drug detoxification by FA.

Understanding the molecular mechanism of mammalian reproduction (puberty and prolificacy) will play a part in improving animal reproductive performance. GLUD1 (glutamate dehydrogenase 1) is important for mammalian reproduction, as shown in previous studies; however, its roles in puberty and prolificacy have rarely been reported. In this study, we designed seven pairs of primers (P1 to P7) for cloning and sequencing genomic DNA of Jining Grey goats and Liaoning Cashmere goats. Primer 8 (P8) was designed to detect single nucleotide polymorphism (SNP) of the GLUD1 in both sexually precocious and high-fecundity breeds (Jining Grey, Nanjiang Brown and Matou goats) and sexually late-maturing and low-fecundity breeds (Liaoning Cashmere, Inner Mongolia Cashmere and Taihang goats) by PCR-RFLP (restriction fragment length polymorphism). The real-time quantitative polymerase chain reaction (RT-qPCR) technique was used to detect the expression of GLUD1 in a variety of tissues. The results showed that the A197C mutation was only found in the amplification product of P6. For this SNP locus, only two genotypes (AA and AC) were detected in Nanjiang Brown goats, while three genotypes (AA, AC and CC) were detected in the other five breeds. In Jining Grey goats, the frequency of genotypes AA, AC and CC was 0.69, 0.26 and 0.05, respectively. In Jining Grey goats, AA genotype had 0.54 (P<0.05) and 0.3 (P<0.05) more kids than the CC and AC genotype, respectively, and no significant difference (P>0.05) was found in kidding number between the AC and CC genotype. GLUD1 was expressed in five tissues of different developmental stages. The expression level of GLUD1 in the hypothalamus was higher than that in the other four tissues except during puberty of Liaoning Cashmere goats. In puberty in goats, GLUD1 expression was significantly higher in ovaries than that in the juvenile period (P<0.01). RT-qPCR results showed that the expression of GLUD1 in ovaries may relate to the puberty of goats. The present study preliminarily indicated that there might be an association between the 197 locus of GLUD1 and sexual precocity in goats, and allele A of GLUD1 was a potential DNA marker for improving kidding number in Jining Grey goats.

Skeletal muscle growth and development from embryo to adult consists of a series of carefully regulated changes in gene expression. This study aimed to identify candidate genes involved in Haiyang Yellow Chickens' growth and to understand the regulatory role of the key gene ALOX5 (arachidonate 5-lipoxygenase) in myoblast proliferation and differentiation. In order to search the key candidate genes in the process of muscle growth and development, RNA sequencing was used to compare the transcriptomes of chicken muscle tissues at four developmental stages and to analyze the effects of ALOX5 gene interference and overexpression on myoblast proliferation and differentiation at the cellular level. The results showed that 5743 differentially expressed genes (DEGs) (|fold change| ≥ 2; FDR ≤ 0.05) were detected by pairwise comparison in male chickens. Functional analysis showed that the DEGs were mainly involved in the processes of cell proliferation, growth, and developmental process. Many of the DEGs, such as MYOCD (Myocardin), MUSTN1 (Musculoskeletal Embryonic Nuclear Protein 1), MYOG (MYOGenin), MYOD1 (MYOGenic differentiation 1), FGF8 (fibroblast growth factor 8), FGF9 (fibroblast growth factor 9), and IGF-1 (insulin-like growth factor-1), were related to chicken growth and development. KEGG pathway (Kyoto Encyclopedia of Genes and Genomes pathway) analysis showed that the DEGs were significantly enriched in two pathways related to growth and development: ECM-receptor interaction (Extracellular Matrix) and MAPK signaling pathway (Mitogen-Activated Protein Kinase). With the extension of differentiation time, the expression of the ALOX5 gene showed an increasing trend, and it was found that interference with the ALOX5 gene could inhibit the proliferation and differentiation of myoblasts and that overexpression of the ALOX5 gene could promote the proliferation and differentiation of myoblasts. This study identified a range of genes and several pathways that may be involved in regulating early growth, and it can provide theoretical research for understanding the regulation mechanism of muscle growth and development of Haiyang Yellow Chickens.

MicroRNAs are involved in a series of biological processes, such as proliferation, differentiation and apoptosis of primary myoblasts. The research group found that miR-214 is highly expressed in chicken primary myoblasts (CPMs), so we used miR-214 as a starting point to explore the biological function of miR-214 in skeletal muscle growth and development. In this experiment, CPMs were cultured in vitro; miR-214 was overexpressed in CPMs; and cell samples were collected for subsequent transcriptome sequencing (RNA-seq). After miR-214 overexpression, we identified 97 differentially expressed genes (DEGs), of which 21 DEGs were up-regulated and 76 DEGs were down-regulated. After bioinformatics analysis, these DEGs were found to be significantly enriched in myofibrils, muscle system processes, myofibril assembly and other biological processes related to muscle development. The significantly enriched KEGGs include focal adhesion and type II diabetes mellitus. The protein network of DEGs was drawn by STRING and Cytoscape software, and 5 DEGs were randomly selected to verify the sequencing results by real-time fluorescence quantification. CAV3 is not only an important node protein in the protein network but also a member of the focal adhesion signaling pathway. It is speculated that miR-214 may regulate muscle development through the focal adhesion signaling pathway.

In the design of retail counter layout, visitor flow is crucial as it greatly impacts the product exposure, sales expectation, and shopping experience.These factors can be expressed through crowd flow-related indicators, including flow speed, acceleration, visit count, and demand fulfillment degree.Although these indicators can be obtained through crowd simulation and be optimized with genetic algorithm, layout optimization may require hundreds of iterations.This means that simulation can take a long time, hindering the efficiency of layout optimization.To address this issue, we accelerated simulation through a surrogate model and proposed a data-driven layout design and optimization workflow.Firstly, we generalized common plan in the real world and designed an automatic generative parametric model to generate random layouts.Next, we obtained multiple crowd flow-related indicators through batch simulation with PedSim Pro.We then collected data and trained a generative adversarial network (GAN) as a surrogate model to capture the relationship between multiple indicators at different positions of regions of interest and the geometric features of counter layout.The trained model can be used with genetic algorithms for automatic optimization to assist designers in obtaining the best layout.Compared to crowd simulation, our trained GAN model is hundreds of times faster in predicting crowd flow-related indicators and has a high predictive accuracy performance with R 2 =0.7.The proposed workflow can significantly improve the optimization process in retail counter layout design.

Major depression (MDD) and generalized anxiety disorder (GAD) have become one of the leading global causes of disability and both are characterized by marked interpersonal and social impairments. However, despite high comorbidity and overlapping social-emotional deficits, it remains unclear whether MDD and GAD share a common neural basis during interpersonal processing. In the present study, we combined an emotional face processing paradigm with fMRI and dimensional and categorical analyses in a sample of unmedicated MDD and GAD patients (N = 72) as well as healthy controls (N = 35). No group differences were found in categorical analyses. However, the dimensional analyses revealed that dorsolateral prefrontal cortex (dlPFC) reactivity to sad facial expressions was positively associated with depression symptom load, yet negatively associated with anxiety symptom load in the entire sample. On the network level depression symptom load was positively associated with functional connectivity between the bilateral amygdala and a widespread network including the anterior cingulate and insular cortex. Together, these findings suggest that the dlPFC - engaged in cognitive and emotional processing - exhibits symptom- and emotion-specific alteration during interpersonal processing. Dysregulated communication between the amygdala and core regions of the salience network may represent depression-specific neural dysregulations.