Deciphering Mechanisms of Adipocyte Differentiation in Abdominal Fat of Broilers.

The excessive deposition of abdominal fat tissue (AFT) in broilers has emerged as a major concern in the poultry industry. Despite some progress in recent years, the molecular mechanisms underlying AFT development remain ambiguous. The current study combined RNA-seq with transposase-accessible chromatin sequencing (ATAC-seq) to map the dynamic profiling of chromatin accessibility and transcriptional reprogramming in AFT adipocyte differentiation in broilers at day 3 (D3) and D14. Our results found that the levels of CDK1 and PCNA were down-regulated at D14, D28, and D42 compared to D3, while the levels of C/EBPα and FABP4 were up-regulated at D14 and D42 compared to D3. Meanwhile, PPARγ was significantly up-regulated at D28 and D42. RNA-seq of AFT identified 1705 up-regulated and 1112 down-regulated differential expression genes (DEGs) between D3 and D14. Pathways based on up-regulated DEGs mainly enriched some pathways related to adipocyte differentiation, while down-regulated DEGs pointed to DNA replication, cell cycle, and gap junction. Gene set enrichment analysis (GSEA) revealed that DNA replication and the cell cycle were down-regulated at D14, while the insulin signaling pathway was up-regulated. In the OA-induced immortalized chicken preadipocyte (ICP2) model, protein dynamic changes were consistent with AFT from D3 to D14. Same pathways were enriched in ICP2. In addition, based on overlapped DEGs from AFT and ICP2, enriched pathways related to adipocyte differentiation or proliferation mentioned above were all involved. A total of 1600 gain and 16727 loss differential peaks (DPs) were identified in ICP2 by ATAC-seq. Predicted genes from DPs at the promoter regions were enriched in glycerophospholipid metabolism, TGF-ß signaling, FoxO signaling, and ubiquitin-mediated proteolysis. DNA motifs predicted 159 transcription factors (TFs) based on gain and loss peaks from the promoter regions, where 1 and 10 TFs were overlapped with up or down TFs from DEGs. Overall, this study presents a framework for the comprehension of the epigenetic regulatory mechanisms of adipocyte differentiation and identifies candidate genes and potential TFs involved in AFT adipocyte differentiation in broilers.

Predicting the Ki-67 proliferation index in cervical cancer: a preliminary comparative study of four non-Gaussian diffusion-weighted imaging models combined with histogram analysis.

Background: The prognosis for patients with cervical cancer (CC) is strongly correlated with the Ki-67 proliferation index (PI). However, the Ki-67 PI obtained through biopsy has certain limitations. The non-Gaussian distribution diffusion model of magnetic resonance imaging (MRI) may play an important role in characterizing tissue heterogeneity. At present, there are limited data available concerning the prediction of Ki-67 PI using models based on histogram features of non-Gaussian diffusion distribution. This study aimed to determine whether preoperative histogram features from multiple non-Gaussian models of diffusion-weighted imaging can predict the Ki-67 PI in patients with CC. Methods: Our cross-sectional prospective study recruited a total of 53 patients suspected of having CC who underwent 3.0-T MRI at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2022 and January 2023. Fifteen b values (0-4,000 s/mm2) were used for diffusion-weighted imaging. A total of nine parameters from four non-Gaussian diffusion-weighted imaging models, including continuous-time random walk (CTRW), diffusion kurtosis imaging (DKI), fractional order calculus (FROC), and intravoxel incoherent motion (IVIM), were used. Whole-tumor volumetric histogram analysis of these parameters was then obtained. In logistic regression, significant histogram characteristics were statistically examined across two groups to build the final prediction model. To assess diagnostic parameters of the proposed model in the diagnosis of the Ki-67 PI, along with the sensitivity, specificity, and diagnostic accuracy of these various parameters from the four models, receiver operating feature analysis was applied. Results: Among the 53 patients (55.3±9.6 years, ranging from 23 to 79 years) included in the study, 15 had a Ki-67 PI ≤50% and 38 had a Ki-67 PI >50%. Univariable analysis determined that 12 histogram features were statistically different between the two groups. In multivariable logistic regression, we ultimately selected 6 histogram features to construct the final prediction model, with CTRW_α_10th percentile [odds ratio (OR) =0.955; 95% confidence interval (CI): 0.92-0.99; P=0.019], CTRW_α_robust mean absolute deviation (OR =0.893; 95% CI: 0.81-0.99; P=0.028), and CTRW_α_uniformity (OR =0.000, 95% CI: 0.00-0.90, P=0.047) being the independent predictive variables. The area under the curve of the combined prediction model was 0.845 (95% CI: 0.74-0.95), with a sensitivity of 78.9% (95% CI: 0.63-0.90), a specificity of 86.7% (95% CI: 0.60-0.98), an accuracy of 81.1% (95% CI: 0.68-0.91), a positive predictive value of 93.8% (95% CI: 0.79-0.99), and a negative predictive value of 61.9% (95% CI: 0.38-0.82). Conclusions: The histogram features of multiple non-Gaussian diffusion-weighted imaging can help to predict the Ki-67 PI of CC, providing a new method for the noninvasive evaluation of critical biological features of CC.

Inhibition of HOXC11 by artesunate induces ferroptosis and suppresses ovarian cancer progression through transcriptional regulation of the PROM2/PI3K/AKT pathway.

BACKGROUND: Ferroptosis, a non-apoptotic form of regulated cell death, plays a critical role in the suppression of various tumor types, including ovarian cancer. Artesunate (ART), a derivative of artemisinin, exhibits extensive antitumor effects and is associated with ferroptosis. This study aimed to investigate the mechanisms through which ART induces ferroptosis to inhibit ovarian cancer. METHODS: RNA sequencing was conducted to identify differentially expressed genes associated with ART-induced ferroptosis. Dual-luciferase reporter assays and electrophoretic mobility shift assays were performed to confirm the interaction between Homeobox C11 (HOXC11) and the Prominin 2 (PROM2) promoter. Cell Counting Kit-8 (CCK-8) assays, flow cytometry, and wound healing assays were used to analyze the antitumor effects of ART. Western blot, biochemical assays and transmission electron microscope were utilized to further characterize ART-induced ferroptosis. In vivo, the effects of ART on ferroptosis were examined using a xenograft mouse model. RESULTS: RNA sequencing analysis revealed that the HOXC11, PROM2 and Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) pathways were downregulated by ART. HOXC11 was found to regulate PROM2 expression by binding to its promoter directly. HOXC11 overexpression reversed ART-induced effects on ovarian cancer cell proliferation, migration, apoptosis and ferroptosis by activating the PROM2/PI3K/AKT signaling axis. Conversely, silencing PROM2 in HOXC11-overexpressing cells restored ART-induced ferroptosis and its associated antitumor effects by inhibiting the PI3K/AKT pathway. Consistently, in vivo studies using a xenograft mouse model confirmed that ART-induced tumor inhibition was mediated by ferroptosis through the suppression of the HOXC11/PROM2/PI3K/AKT pathway. CONCLUSION: This study identifies the HOXC11/PROM2/PI3K/AKT axis as a novel regulatory mechanism underlying ART-induced ferroptosis in ovarian cancer. Targeting the HOXC11/PROM2 axis may represent a promising therapeutic strategy for enhancing ferroptosis, offering new insights for the treatment of ovarian cancer.

Genetic architectures of the human hippocampus and those involved in neuropsychiatric traits.

BACKGROUND: The hippocampus, with its complex subfields, is linked to numerous neuropsychiatric traits. While most research has focused on its global structure or a few specific subfields, a comprehensive analysis of hippocampal substructures and their genetic correlations across a wide range of neuropsychiatric traits remains underexplored. Given the hippocampus's high heritability, considering hippocampal and subfield volumes (HASV) as endophenotypes for neuropsychiatric conditions is essential. METHODS: We analyzed MRI-derived volumetric data of hippocampal and subfield structures from 41,525 UK Biobank participants. Genome-wide association studies (GWAS) on 24 HASV traits were conducted, followed by genetic correlation, overlap, and Mendelian randomization (MR) analyses with 10 common neuropsychiatric traits. Polygenic risk scores (PRS) based on HASV traits were also evaluated for predicting these traits. RESULTS: Our analysis identified 352 independent genetic variants surpassing a significance threshold of 2.1 × 10-9 within the 24 HASV traits, located across 93 chromosomal regions. Notably, the regions 12q14.3, 17q21.31, 12q24.22, 6q21, 9q33.1, 6q25.1, and 2q24.2 were found to influence multiple HASVs. Gene set analysis revealed enrichment of neural differentiation and signaling pathways, as well as protein binding and degradation. Of 240 HASV-neuropsychiatric trait pairs, 75 demonstrated significant genetic correlations (P < 0.05/240), revealing 433 pleiotropic loci. Particularly, genes like ACBD4, ARHGAP27, KANSL1, MAPT, ARL17A, and ARL17B were involved in over 50 HASV-neuropsychiatric pairs. Leveraging Mendelian randomization analysis, we further confirmed that atrophy in the left hippocampus, right hippocampus, right hippocampal body, and right CA1-3 region were associated with an increased risk of developing Parkinson's disease (PD). Furthermore, PRS for all four HASVs were significantly linked to a higher risk of Parkinson's disease (PD), with the highest hazard ratio (HR) of 1.30 (95% CI 1.18-1.43, P = 6.15 × 10⁻8) for right hippocampal volume. CONCLUSIONS: These findings highlight the extensive distribution of pleiotropic genetic determinants between HASVs and neuropsychiatric traits. Moreover, they suggest a significant potential for effectively managing and intervening in these diseases during their early stages.

Multitype view of knowledge contrastive learning for recommendation.

Graph Neural Networks (GNNs) are playing an increasingly vital role in the field of recommender systems. To improve knowledge perception within GNNs, contrastive learning has been applied and has proven to be highly effective. GNNs have the ability to aggregate diverse knowledge and integrate topologies, while contrastive learning seeks supervisory signals from the model data. The combination of GNNs and contrastive learning can improve recommendations. However, thoughtless or incomplete contrastive learning settings limit the effectiveness of GNNs-based recommender systems in learning knowledge from knowledge and interaction graphs. To better exploit the valuable information within knowledge graphs, we propose a novel multitype view of knowledge contrastive learning for recommendations (MVKC) model. The MVKC model generates hierarchical views and augmented views in two modules, performing cross-hierarchical-view and cross-augmented-view contrastive learning and mining graph features in a self-supervised manner. The hierarchical views consist of global and local parts at multiple levels, while the augmented views are fused from the augmented knowledge graph and augmented interaction graph in our augmented processing. These features allow the MVKC model to alleviate the sparsity of user-item interaction graphs, suppress knowledge graph noise, and filter long-tail entities, which has been proven extremely important for a recommendation. The MVKC model also has strong anti-interference ability and robustness, which is crucial for a well-established model. Our experiments with three public datasets demonstrate that the MVKC model outperforms current state-of-the-art methods.

Poultry Nutrition: Achievement, Challenge and Strategy.

Poultry, a vital economic animal, provide a high quality protein source for human nutrition. Over the past decade, the poultry industry has witnessed substantial achievements in breeding, precision feeding, and welfare farming. However, there are still many challenges restricting the sustainable development of the poultry industry. Firstly, overly focused breeding strategies on production performance have been shown to induce metabolic diseases in poultry. Secondly, a lack of robust methods for assessing the nutritional requirements poses a challenge to the practical implementation of precision feeding. Thirdly, antibiotic alternatives and feed safety management remain pressing concerns within the poultry industry. Lastly, environmental pollution and inadequate welfare management in farming have a negative effect on poultry health. Despite numerous proposed strategies and innovative approaches, each faces its own set of strengths and limitations. In this review, we aim to provide a comprehensive understanding of the poultry industry over the past decade, by examining its achievements, challenges, and strategies, in order to guide its future direction.

Eukaryotic plankton species diversity and community structure in the Xiao Jiang River (the primary tributary of Upper Yangtze River), Yunnan.

The Xiao Jiang River, as a crucial element of ecological restoration in the upper reaches of the Yangtze River, plays an indispensable role in agricultural water utilization and water ecology within its watersheds. The water quality status of the Xiao Jiang River not only impacts local water-ecological equilibrium and economic benefits but also holds paramount importance for sustaining ecosystem health in the Yangtze River basin. Plankton surveys and environmental physicochemical detection were conducted in the major channel region of the Xiao Jiang River in dry and wet periods in 2022 to better understand the diversity of eukaryotic plankton and its community structure characteristics. Environmental DNA is an emerging method that combines traditional ecology with second-generation sequencing technology. It can detect species from a single sample that are difficult to find by traditional microscopy, making the results of plankton diversity studies more comprehensive. For the first time, environmental DNA was used to investigate eukaryotic plankton in the Xiao Jiang River . The results showed that a total of 881 species of plankton from 592 genera in 17 phyla were observed. During the dry period, 480 species belonging to 384 genera within17 phyla were detected, while, during the wet period, a total of 805 species belonging to 463 genera within 17 phyla were recorded. The phylum Ciliophora dominated the zooplankton, while the phylum Chlorophyta and Bacillariophyta dominated the phytoplankton. The presence of these dominant species indicate that the water quality conditions in the study area are oligotrophic and mesotrophic. Principal coordinate analysis and difference test showed that the number of plankton ASVs, abundance, species richness, dominating species, and diversity indices differed between the dry and wet periods. Spearman correlation analysis and redundancy analysis (RDA) of relative abundance data with environmental physicochemical factors revealed that water temperature (WT), dissolved oxygen (DO), potential of hydrogenacidity (pH), ammonia nitrogen (NH3-N), total nitrogen (TN), electrical conductivity (EC) and the determination of redox potential (ORP) were the main environmental physicochemical factors impacting the plankton community structure. The results of this study can serve as a provide data reference at the plankton level for water pollution management in the Xiao Jiang River, and they are extremely important for river ecological restoration and biodiversity recovery in the Yangtze River basin.

An atlas of genetic effects on cellular composition of the tumor microenvironment.

Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.

Lactiplantibacillus plantarum JM113 alleviates deoxynivalenol induced intestinal damage by microbial modulation in broiler chickens.

Deoxynivalenol (DON) contamination causes the grievous injury in public and animal health, poultry suffer from the greater toxin challenge. Probiotic have been considered as a potential way to mitigate the deleterious effects of DON. In this study, a total of 144 1-day-old Arbor Acres chickens were randomly assigned into 3 groups: control group, DON group (5 mg/kg DON diet), DJ group (1×109 cfu Lactiplantibacillus plantarum JM113/kg DON diet). The results showed that Lactiplantibacillus plantarum JM113 (L. plantarum JM113) increased the growth performance of 21-day-old broilers that challenged by the DON (P < 0.05), and the DON-induced disorder of jejunal morphology was recovered in DJ group (P < 0.05). Compared with the DON group, the mRNA and protein levels of Nrf2 and NQO-1 were upregulated in jejunum of DJ group broilers (P < 0.05). Meanwhile, administration of L. plantarum JM113 effectively increased the expression level of barrier-related genes, and the protein abundance of occludin and claudin1 (P < 0.05). L. plantarum JM113 restored the mRNA and protein abundance of PCNA, and proliferation-linked gene (Lgr5 and Bmi1) expression levels in jejunum of DON-insulted broilers (P < 0.05). Furthermore, administration of L. plantarum JM113 significantly enhanced the relative abundance of s_Limosilactobacillus_reuteri in jejuna of DON-challenged broilers (P < 0.05). Spearman correlation analysis showed that s_Limosilactobacillus_reuteri was positively associated with the jejunal barrier related genes (P < 0.05). In conclusion, L. plantarum JM113 alleviated the toxic effects of DON by regulating the jejunal function through microbial adjustment. Our findings proposed a viable approach to mitigating the adverse effects of deoxynivalenol exposure in broilers.

Urban Flood Resilience Evaluation Based on Heterogeneous Data and Group Decision-Making.

In recent years, urban floods have occurred frequently in China. Therefore, there is an urgent need to strengthen urban flood resilience. This paper proposed a hybrid multi-criteria group decision-making method to assess urban flood resilience based on heterogeneous data, group decision-making methodologies, the pressure-state-response model, and social-economic-natural complex ecosystem theory (PSR-SENCE model). A qualitative and quantitative indicator system is formulated using the PSR-SENCE model. Additionally, a new weighting method for indicators, called the synthesis weighting-group analytic hierarchy process (SW-GAHP), is proposed by considering both intrapersonal consistency and interpersonal consistency of decision-makers. Furthermore, an extensional group decision-making technology (EGDMT) based on heterogeneous data is proposed to evaluate qualitative indicators. The flexible parameterized mapping function (FPMF) is introduced for the evaluation of quantitative indicators. The normal cloud model is employed to handle various uncertainties associated with heterogeneous data. The evaluations for Beijing from 2017 to 2021 reveal a consistent annual improvement in urban flood resilience, with a 14.1% increase. Subsequently, optimization recommendations are presented not only for favorable indicators such as regional economic status, drainability, and public transportation service capacity but also for unfavorable indicators like flood risk and population density. This provides a theoretical foundation and a guide for making decisions about the improvement of urban flood resilience. Finally, our proposed method shows superiority and robustness through comparative and sensitivity analyses.

Silver Nanoparticles Exposure Impairs Cardiac Development by Suppressing the Focal Adhesion Pathway in Zebrafish.

Introduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood. Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h. Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish. Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.

Butyric acid reduced lipid deposition in immortalized chicken preadipocyte by inhibiting cell proliferation and differentiation.

The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 µM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins.

Dietary betaine supplementation improved egg quality and gut microbes of laying hens under dexamethasone-induced oxidative stress.

Oxidative stress is a frequent concern in the breeding of laying hens, and limit the healthy development of poultry. Dexamethasone (DXM) has been demonstrated to induce oxidative stress. Conversely, betaine is an alkaloid with a potent antioxidant activity. The study was designed to investigate the ameliorative effect of betaine on DXM-induced oxidative stress in laying hens. The results revealed that DXM treatment significantly decreased laying rate, shell strength, albumen height, Haugh unit, egg weight, folk weight and albumen weight, alongside increased malondialdehyde (MDA) and decreased total antioxidant capacity (T-AOC) in serum and liver (P < 0.05). In contrast, dietary betaine addition reversed those parameters mentioned above (P < 0.05). Hepatic RNA-seq analysis showed that there existed 110 up- and 88 down-regulated genes in DXM group when compared with the control. Meanwhile there were 117 upregulation and 169 downregulation genes in BT group when compared with DXM group. Besides, we found that dietary betaine addition significantly down-regulated cell adhesion molecules, glycerolipid metabolism and glycolysis gluconeogenesis pathways. In addition, a total of 44 and 94 differential metabolites were identified respectively from Con vs. DXM and DXM vs BT. More importantly, dietary betaine addition significantly increased the levels of pantothenic acid, gamma-Aminobutyric acid, equol and choline, all of which were related to antioxidant and anti-inflammatory properties. Furthermore, gut microbiota analysis indicated that the Chao and Observed_species indexes were remarkably higher in BT group (P<0.05). Heatmap analysis revealed that Subdoligranulum, Prevotella, Blautia, YRC22, Bacteroides, Ruminococcus and Coprococcus were notably restored in BT group (P<0.05). Taken together, our findings collectively illustrate that dietary betaine addition could attenuate DXM-induced oxidative stress, improve egg quality and gut microbes of laying hens.

The synergistic effect of triglyceride-glucose index and HbA1c on blood pressure control in patients with hypertension: a retrospective cohort study.

Triglyceride-Glucose Index (TyG index) and HbA1c are metabolic risk factors associated with insulin resistance (IR), which have been confirmed to be independently correlated with the incidence of hypertension. However, there is limited research specifically focusing on the interaction between these two metabolic risk factors in hypertensive populations. Currently, it remains unclear how the metabolic indicators TyG index and HbA1c affect BP control in individuals with hypertension. This study aims to investigate the value and interaction of TyG index and HbA1c in blood pressure (BP) control among hypertensive patients. The results are conducive to enhancing the effectiveness of clinical BP control for individuals with hypertension. This cohort study included 99,336 adults diagnosed with hypertension. Participants were grouped according to the median of TyG index and HbA1c. The main endpoint is inadequate BP control. Multivariable-adjusted risk ratios and multivariable Cox regression analysis were used to represent the relationship between BP control levels and metabolic risk factors. Finally, we evaluated the interaction between TyG index and HbA1c in the population with inadequate BP control. This study confirmed that TyG index and HbA1c, as metabolic risk factors, are independently associated with poor BP control (P < 0.05). In multivariable Cox regression analysis, it was found that TyG index and HbA1c were significantly associated with poor BP control. In the male elderly population, HbA1c was significantly associated with poor BP control (P = 0.029).

The potential toxic effects of estrogen exposure on neural and vascular development in zebrafish.

Estrogens and estrogenic chemicals are endocrine-disrupting chemicals (EDCs). The potential toxicity of EDCs to humans and aquatic organisms has become increasingly concerning. However, at present, the potential toxic mechanisms of EDCs on neural and vascular development are still being fully investigated. During the study, we utilized zebrafish to assess the developmental neural and vascular toxicity of different estrogens. The results indicated that zebrafish treated with different estrogens, especially E2, exhibit developmental malformations, including increased mortality, decreased body length, decreased heart rate, aberrant swimming behavior, and increased developmental malformations, including spinal curvature (SC), yolk edema (YE) and pericaidial edema (PE), in a dose-dependent manner with 72 h-treated. Further morphological evaluation revealed that E2 exposure significantly induced motor neural abnormalities in zebrafish embryos. In addition, treated with these three estrogens also impaired the vascular development in the early stage of zebrafish embryos. Mechanistically, the identification of downstream factors revealed that several key neural and vascular development-related genes, including syn2a, gfap, gap43, shha, kdr, flt1 and flt4, were transcriptionally downregulated after estrogen exposure in zebrafish, suggesting that estrogen exposure might cause neural and vascular toxicity by interfering the mRNA levels of genes relevant to neural and vascular development.

Acute indomethacin exposure impairs cardiac development by affecting cardiac muscle contraction and inducing myocardial apoptosis in zebrafish (Danio rerio).

The accumulation of the active pharmaceutical chemical in the environment usually results in environmental pollution to increase the risk to human health. Indomethacin is a non-steroidal anti-inflammatory drug that potentially causes systemic and developmental toxicity in various tissues. However, there have been few studies for its potential effects on cardiac development. In this study, we systematically determined the cardiotoxicity of acute indomethacin exposure in zebrafish at different concentrations with morphological, histological, and molecular levels. Specifically, the malformation and dysfunction of cardiac development, including pericardial oedema, abnormal heart rate, the larger distance between the venous sinus and bulbus arteriosus (SV-BA), enlargement of the pericardial area, and aberrant motor capability, were determined after indomethacin exposure. In addition, further investigation indicated that indomethacin exposure results in myocardial apoptosis in a dose-dependent manner in zebrafish at early developmental stage. Mechanistically, our results revealed that indomethacin exposure mainly regulates key cardiac development-related genes, especially genes related to the cardiac muscle contraction-related signaling pathway, in zebrafish embryos. Thus, our findings suggested that acute indomethacin exposure might cause cardiotoxicity by disturbing the cardiac muscle contraction-related signaling pathway and inducing myocardial apoptosis in zebrafish embryos.