👤 Weiyi Song

The extensive co-occurrence of cardiovascular diseases (CVDs), as evidenced by epidemiological studies, is supported by positive genetic correlations identified in comprehensive genetic investigations, suggesting a shared genetic basis. However, the precise genetic mechanisms underlying these associations remain elusive. By assessing genetic correlations, genetic overlap, and causal connections, we aim to shed light on common genetic underpinnings among major CVDs. Employing multi-trait analysis, we pursue diverse strategies to unveil shared genetic elements, encompassing SNPs, genes, gene sets, and functional categories with pleiotropic implications. Our study systematically quantifies genetic overlap beyond genome-wide genetic correlations across CVDs, while identifying a putative causal relationship between coronary artery disease (CAD) and heart failure (HF). We then pinpointed 38 genomic loci with pleiotropic influence across CVDs, of which the most influential pleiotropic locus is located at the LPA gene. Notably, 12 loci present high evidence of multi-trait colocalization and display congruent directional effects. Examination of genes and gene sets linked to these loci unveiled robust associations with circulatory system development processes. Intriguingly, distinct patterns predominantly driven by atrial fibrillation, coronary artery disease, and venous thromboembolism underscore the significant disparities between clinically defined CVD classifications and underlying shared biological mechanisms, according to functional annotation findings. Show less

Intensive poultry farming has significantly increased the incidence of lipid metabolic disorders, severely compromising the economic benefits of poultry industry. Currently, gamma-aminobutyric acid (GABA) is primarily used to mitigate adverse effects of heat stress in poultry, while the effects and mechanisms of GABA on lipid metabolism disorders remain underexplored. Lactobacillus plantarum (L. plantarum) serves as a significant source of GABA and is widely used in the livestock industry. This study therefore examines the effects of postbiotic GABA and the GABA-producing probiotic L. plantarum 1-2-3 on abdominal adipose tissue of laying hens following corticosterone-induced stress. To this end, hens subjected to corticosterone subcutaneous injections (4 mg/kg of body weight) were respectively received GABA (100 mg/kg BW) or L. plantarum 1-2-3 (1 × 10⁹ CFU/day). Results demonstrated that both GABA and L. plantarum 1-2-3 alleviated corticosterone-induced lipid metabolism disorders and reduced adipocyte size in abdominal fat. Additionally, expression analyses of genes and proteins related to lipid metabolism (PPARγ, C/EBPα, CD36, LPL, ATGL, and HSL) further showed that GABA and L. plantarum 1-2-3 inhibited excessive deposition of abdominal lipids in laying hens by suppressing adipogenesis and lipogenesis, while promoting lipolysis. Moreover, GABA and L. plantarum 1-2-3 both mitigated lipid deposition-induced inflammation and oxidative damage by normalizing macrophage infiltration and improving antioxidative enzyme activities (GSH-Px, T-SOD, CAT). These findings demonstrate the efficacy of GABA and L. plantarum 1-2-3 in alleviating lipid metabolism disorders in the abdominal adipose tissue of laying hens, suggesting their promise as nutritional supplements for counteracting stress-induced metabolic dysfunction. Show less

Lymphoplasmacytic Lymphoma (LPL) with immunoglobulin (Ig)A paraprotein is rare. When plasma cells dominate, the diagnosis becomes more challenging. We reported a case of a 71-year-old male with elevated creatinine, splenomegaly, monoclonal IgA, and MYD88 mutation. Only monoclonal plasma cells were detected first, leading to a misdiagnosis of multiple myeloma. When progressive spleen enlargement was observed, re-evaluation revealed the emergence of monoclonal lymphocytes and the diagnosis was revised to LPL. The addition of rituximab to DVD regimen led to a partial response. For cases where an initial definitive diagnosis cannot be established, close follow-up is required for timely diagnosis revision and therapeutic adjustment. Show less

In peripheral tissues, an endothelial cell (EC) protein, GPIHBP1, captures lipoprotein lipase (LPL) from the interstitial spaces and transports it to the capillary lumen. LPL mediates the margination of triglyceride-rich (TG-rich) lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. TRL-derived fatty acids are used for fuel in oxidative tissues or stored in adipose tissue. In mice, GPIHBP1 is absent from capillary ECs of the brain (which uses glucose for fuel); consequently, LPL and TRL margination are absent in mouse brain capillaries. However, because fatty acids were reported to play signaling roles in the brain, we hypothesized that LPL-mediated TRL processing might occur within specialized vascular beds within the central nervous system. Here, we show that GPIHBP1 is expressed in capillary ECs of human and mouse choroid plexus (ChP) and that GPIHBP1 transports LPL (produced by adjacent ChP cells) to the capillary lumen. The LPL in ChP capillaries mediates both TRL margination and processing. Intracapillary LPL and TRL margination are absent in the ChP of Gpihbp1-/- mice. GPIHBP1 expression, intracapillary LPL, and TRL margination were also observed in the median eminence and subfornical organ, circumventricular organs implicated in the regulation of food intake. Show less

Bacteroides-centric gut dysbiosis reported to exacerbates liver cirrhosis via inflammation and fibrosis, therefore utilizing Bacteroides species as microbiome-based therapeutic logical to mitigate disease progression. Feces were collected from 52 Healthy and 144 Liver cirrhosis individuals for V3-V4 dependent 16rRNA-bsed comparative metagenomics analysis, followed a by microbiome depleted and non-depleted DDC mice model to explain the role of Bacteroidetes phylum classified microbial species P. plebeius in liver fibrosis pathophysiological pathways. Bacteroides presented cirrhosis-dependent decrease in human and animal microbiome, and negatively correlated to key molecular pattern associated with cirrhosis. P. plebeius significantly reduced in abundance and identified as a microbial biomarker for cirrhosis (AUC = 0.73) and treatment with P. plebeius significantly improved the levels of cirrhosis-related phenotypical and biochemical markers in the microbiome-depleted cirrhosis group. P. plebeius decrease the expression of S100a9, CCR1, ADAM8, TREM2, ITGAM, and MYO5A which are primarily responsible for inducing inflammation in liver cirrhosis. P. plebeius downregulated the fibrosis related genes expression including CD51, PLAT, ITGA3, CXCR4, and TGFBR1 and gene related to extracellular matrix formation including COL1A1, LTBP2, S100A6, and SMCO2. Additionally, P. plebeius treatment decreased the expression of hepatotoxicity-related genes including LPL, KRT18, ALDOA, and MCM10, and increased the expression of FABP1 and RDX. Additionally, P. plebeius normalized the expression of genes connected to two pathophysiological process including TIMP4, TGFB3, S100A8, PLSCR1, MMP8, CXCL4, and BMP. Our study revealed P. plebeius as a multifaceted bio-therapeutic candidate that normalized dysregulated gene expression and reversed hepatic inflammation, fibrogenesis, and hepatotoxicity. Show less

Iodine is an essential micronutrient for developmental processes in the early stages; however, data on the effect of maternal iodine nutrition on milk lipids are limited. We aimed to explore the effect of inadequate and excessive iodine intake on milk lipid metabolism and its mechanisms preliminarily. Rats were treated with different concentrations of potassium iodide water to construct animal models of iodine deficiency and excess. Iodine excess reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels during lactation. Iodine deficiency had no significant effect on blood lipid indicators. In early and late lactation, iodine deficiency and excess inhibited triglyceride (TG) levels in milk; in mid-lactation, the inhibitory effect of iodine deficiency was attenuated. Under iodine deficiency and excess, the level of TG and the expression of THRα1, THRβ1, ACC1, FAS, THRSP, BTN1A1, and ADFP proteins in the mammary gland were decreased during lactation; a decrease in LPL protein expression was observed in early and late lactation; and a decline of XOR protein expression was reported in mid and late lactation. Blood lipid metabolism was less sensitive to iodine deficiency during lactation. Iodine excess has a more profound effect on blood lipid metabolism, causing dyslipidemia in lactating rats. Long-term iodine deficiency and excess may have a negative role in the mechanisms regulating milk lipid synthesis and secretion by affecting thyroid hormones to inhibit the milk TG level. Show less

Chicken meat quality directly influences consumer acceptability and is crucial for the economic success of the poultry industry. Genetics and nutrition are key determinants of the meat quality traits in broilers. This review summarizes the research advances in this field, with a focus on the genetic and nutritional foundations that regulate intramuscular fat (IMF) deposition and meat quality in chickens over the past decade. The effects of embryonic nutrition, both maternal nutrition and in ovo feeding (IOF), on skeletal muscle development, the IMF content, and meat quality traits in broilers are also discussed. In genetics, single-cell RNA sequencing revealed that de novo lipogenesis predominantly occurs in myocytes, which is key to the formation of IMF in chicken muscle tissue. Fatty acid synthase (FASN) is the key enzyme involved in this process. This discovery has reshaped the traditional understanding of intramuscular lipid metabolism in poultry. Key genes, proteins, and pathways, such as FASN, FABP4, PPARG, C/EBPα, SLC27A1; LPL, APOA1, COL1A1; PPAR and ECM-receptor interactions signaling, have been identified to regulate IMF content and distribution by modulating fatty acid metabolism and adipogenesis. LncHLFF was innovatively found to promote ectopic IMF deposition in chickens via exosome-mediated mechanisms without affecting abdominal fat deposition. MiR-27b-3p and miR-128-3p were found to inhibit adipogenic differentiation by targeting PPARG, thereby affecting IMF formation. In nutrition, nutrigenomics research has shown that fructose enhances IMF deposition by activating ChREBP, providing new targets for nutritional interventions. Adjusting dietary components, including energy, protein, amino acids, fatty acids, and phytochemicals (e.g., rutin), has been shown to significantly improve meat quality in broilers. Maternal nutrition (e.g., intake of energy, amino acids, vitamins, and trace elements) and IOF (e.g., N-carbamylglutamate) have also been confirmed to significantly impact offspring meat quality, opening new avenues for improving embryonic nutrition. Based on these significant advancements, this review proposes strategies that integrate genetic and nutritional approaches. These strategies aim to modulate the differentiation fate of paraxial mesenchymal stem cells toward myogenic or adipogenic lineages and the interaction between muscle and adipose tissues. These insights would help to improve meat quality while ensuring the growth performance of broiler chickens. Show less

This study was conducted to investigate the effects of replacing fish meal with either whole-fat or defatted krill powder on the growth, body color, immunity, and related gene expression of red-white koi carp. A total of 630 red-white koi carp with an initial body mass of 13.5 ± 0.05 g were randomly divided into seven groups with three replicates per group and 30 fish per replicate. The control group was fed a basic diet (C0). The other six diets were supplemented with different levels of whole krill meal or defatted krill meal as replacements (10% whole fat, 20% whole fat, 30% whole fat, 10% defatted, 20% defatted, and 30% defatted) in the experimental groups, named W10, W20, W30, D10, D20, and D30, respectively, for a total duration of 60 days. The growth, body color, immunity and gene expression indexes were measured in the koi after completion. The results indicate the following. (1) Compared with C0, the experimental groups of koi showed a significant increase in the specific growth rate (SGR) ( Show less

The purpose of this paper is to comprehensively review the research progress of nattokinase in lowering blood lipid, including its source, structure and physicochemical properties, mechanisms of functions, clinical research status, and safety considerations, so as to provide reference for further research on the application of nattokinase in the treatment of dyslipidemia. Natto is a traditional Japanese fermented food, which is made from soybeans fermented by Bacillus natto. During the fermentation process, natto will produce a variety of biologically active substances, including nattokinase. Nattokinase (NK) is a serine protease with stable enzyme activity and good freeze-thaw tolerance, which exerts lipid-lowering and anti-atherosclerotic effects by activating hormone-sensitive lipase (HSL), inhibiting hydroxymethylglutaryl monoacyl coenzyme A reductase (HMG-CoA reductase), and enhancing lipoprotein lipase (LPL) activity. Large-scale clinical trials have confirmed that nattokinase significantly improves the lipid profile and reduces the atherosclerotic plaque area and intima-media thickness with a favorable safety profile. Compared with traditional lipid-lowering drugs (e.g., statins and fibrates), nattokinase has a multifaceted lipid-lowering mechanism and lower risk of side effects, which makes it suitable for patients intolerant of traditional drugs; when combined with natural products such as statins, fibrates, red yeast, and lifestyle interventions, it can play a synergistic role and further reduce the risk of cardiovascular disease. There are various types of nattokinase preparations on the market, and consumers should choose regular products with high activity and purity, and pay attention to their safety and applicable population. Show less

Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are persistent environmental contaminants linked to adverse health effects, including an increased risk of breast cancer. However, the molecular mechanisms through which PFAS contribute to breast cancer development remain poorly understood. In this study, we employed an integrated approach combining network toxicology, single-cell sequencing, spatial transcriptomics, and molecular simulation to investigate the effects of PFAS on breast cancer. By constructing a protein-protein interaction (PPI) network, we identified six core genes (PPARG, CD36, FABP4, PPARGC1A, LPL, and PCK1) that play a significant role in the development of breast cancer. These genes are involved in key cellular processes such as lipid metabolism, oxidative phosphorylation, and immune regulation, all of which are disrupted by PFAS exposure. Single-cell and spatial transcriptomic analyses revealed that these genes are predominantly expressed in endothelial, myeloid, and cancer-associated fibroblasts within the tumor microenvironment. Molecular simulation further confirmed strong binding energies between PFAS and these target proteins, suggesting direct interactions. Our findings provide novel insights into how PFAS may promote breast cancer progression at the molecular level and highlight the need for further research on environmental pollutants in cancer risk assessment and public health initiatives. Show less

Beef quality is critically determined by intramuscular fat (IMF) deposition. Retinoic acid (RA), the active metabolite of vitamin A, plays an essential regulatory role in IMF development. To systematically investigate RA-mediated regulation of IMF formation in cattle, we established a concentration gradient of RA supplementation and employed a systematic screening approach to identify the optimal dosage for modulating bovine intramuscular adipocytes (IMAs) proliferation and differentiation. Subsequently, leveraging integrated multi-omics approaches, we screened the key downstream molecular targets through which RA governs IMF biosynthesis, and clarified the potential regulatory mechanism of this target. Our experimental data establish that RA promotes the proliferation of IMAs through modulation of G1/S phase progression. Concurrently, RA enhances triglyceride biosynthesis in IMAs by activating PPARγ-mediated cell differentiation and LPL-mediated intracellular lipid accumulation. Integrated transcriptomics and metabonomics analyses identified FABP4, CD36, EBF2, LRP1 and CAV1 as key candidate genes involved in RA-mediated IMF production. Functional interrogation revealed that FABP4 knockdown markedly attenuated lipid accumulation in IMAs, a phenotype rescued through RA supplementation, confirming FABP4 as the critical effector mediating vitamin A's regulation of bovine IMF deposition. These results provide a new understanding of how nutritional factors affect beef quality at the molecular level. Show less

Metabolism alteration is a common complication of rheumatic arthritis (RA). This work investigated the reason behind RA-caused triglyceride (TG) changes. Fresh RA patients' whole blood was transfused into NOD-SCID mice. Metabolism-regulatory tissues were examined after sacrifice. To verify the findings, tissues of the rats with long-lasting adjuvant-induced arthritis (AIA) were analyzed. Some rats were injected with human plasma and GPIHBP1, and their blood TG was monitored. Various cells were stimulated by cytokines or rheumatic subjects' serum. Some pre-adipocytes were cultured by human serum or in the presence of HUVEC cells and GPIHBP1. TG decrease occurred in blood and white adipose tissues (WAT) of the RA blood-transfused NOD-SCID mice and chronic AIA rats. Fatty acids (FA) oxidation in muscles was accelerated a bit, while TG catabolism status in their livers was varied. TNF-α, IL-1β, IL-6 and RA/AIA serum promoted expression of TG utilization-related enzymes and FA uptake transporters in pre-adipocytes, but barely affected LPL. Mild IL-6 stimulus promoted GPIHBP1 release of HUVEC cells. GPIHBP1 was increased in RA serum. This change can decrease blood TG in rats, which was overshadowed by an injection of excessive GPIHBP1. RA serum slightly inhibited LPL secretion in pre-adipocytes. Both HUVEC cells co-culture and GPIHBP1 supplement reduced LPL distribution on pre-adipocytes, and eliminated LPL activity difference between normal and RA serum-treated cells. No TG uptake difference was observed in these circumstances. RA-associated inflammation induces GPIHBP1 secretion of endothelial cells, which facilitates blood TG hydrolysis and uptake to compensate the loss in WAT. Show less

Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (PZI) and trioxytriphenylamine (TOT) ligands, was synthesized. PZI-Au-TOT displays decent thermally activated delayed fluorescence (TADF) with a quantum yield of 93 % in doped film. The crystals of PZI-Au-TOT show simultaneous TADF, polymorphism, and linearly polarized luminescence (LPL). The polymorph-dependent emission properties with widely varied peaks from 560 to 655 nm are attributed to different packing modes in terms of isolated monomers, discrete π-π stacked dimers or dimer PLUS. Two well-defined microcrystals of PZI-Au-TOT exhibit linearly polarized thermally activated delayed fluorescence with a degree of polarization up to 0.64. This work demonstrates that the molecular rotational flexibility of D-M-A type complexes endows an integration of multiple functions into one complex through manipulation of supramolecular aggregation. This type of complexes is expected to serve as a versatile platform for the fabrication of crystal materials for advanced photonic applications. Show less

The microtubule actin crosslinking factor 1 ( Trios-based whole-exome sequencing was performed on a cohort with generalised epilepsy from the China Epilepsy Gene 1.0 project. The spatial-temporal expression, single-cell sequencing and genotype-phenotype correlation were analysed to explore the role of Two de novo heterozygous and eight biallelic Show less

To determine whether insulin controls hepatic de novo lipogenesis (DNL) through an HCF-1-dependent modulation of ChREBP that is distinct from the canonical SREBP1c pathway. AML-12 mouse hepatocytes were subjected to 10 μg/mL insulin and 25 mM glucose for 6 h. IRβ or HCF-1 was knocked down with lentiviral shRNA (≈80 % efficiency). Lipid droplets were quantified by Nile-Red staining; mRNA and protein levels were measured by RT-qPCR, Western blot, immunofluorescence and RNA-seq. Co-immunoprecipitation was used to test complex formation. Insulin reduced lipid accumulation and suppressed ChREBP protein and its nuclear localization in AML-12 hepatocytes without altering SREBP1c. Knock-down of IRβ or HCF-1 abolished insulin-mediated ChREBP suppression, increased lipid droplets and up-regulated lipogenic genes. HCF-1 co-immunoprecipitated with IRβ, indicating formation of an insulin-responsive IRβ/HCF-1 complex that restrains ChREBP-driven lipogenesis. We identify an IRβ/HCF-1/ChREBP regulatory node in hepatocytes that can repress lipogenic genes independently of SREBP1c. The axis constitutes a testable target for understanding selective insulin action on hepatic lipid metabolism and for future in-vivo studies of fatty-liver disease. Show less

Recent advancements in transcriptomic analysis, combined with single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics, have deepened our understanding of the tumor microenvironment and cellular heterogeneity, laying the groundwork for personalized therapies. The aim of this research is to explore the heterogeneity of tumor cells in colorectal cancer (CRC) and evaluate their prognostic value in different therapeutic contexts, emphasizing the impact of tumor cell heterogeneity on disease progression. scRNA-seq alongside spatial transcriptomics was employed to analyze the heterogeneity of tumor cells in CRC, the spatial distribution of tumor cells, and their interactions with the microenvironment. We identified nine distinct tumor cell subtypes, with MLXIPL + neoplasm prevalent in advanced CRC, while ADH1C + and MUC2 + neoplasms were more common in early-stage CRC. MLXIPL + neoplasm was significantly associated with chemotherapy and targeted therapy efficacy. Analysis of spatial transcriptomics indicated that MLXIPL + neoplasm is located in the core area of the tumor cells. We developed a 13-gene prognostic signature (PS) using machine learning algorithm (StepCox backward), which predicts the prognosis of CRC patients. Furthermore, the patients with low PS score demonstrated higher immune cell infiltration and immune regulatory factors, suggesting enhanced immune surveillance and treatment response. The findings highlight the critical role of tumor cell heterogeneity in CRC progression and treatment response, suggesting the need for personalized therapeutic strategies targeting different subpopulations. The constructed PS demonstrates significant clinical application value in predicting patient prognosis. Show less

Hypertrophic cardiomyopathy (HCM), characterized by ventricular hypertrophy and fibrosis, frequently progresses to heart failure. Although metabolic dysregulation is implicated in HCM pathophysiology, the role of PDK4 (pyruvate dehydrogenase kinase 4), a key regulator of cardiac glucose and fatty acid oxidation, in HCM-related heart failure remains unknown. Single-nucleus RNA sequencing was performed to analyze gene expression in patients with HCM (n=12), categorized into the following groups: normal, reduced, and heart failure. We validated our findings in additional cohorts of patients undergoing septal resection or heart transplantation. Cardiac-specific Single-nucleus RNA sequencing identified distinct cardiomyocyte clusters, with cardiomyocyte cluster 4 ( Our findings highlight metabolic disturbance, specifically PDK4-driven suppression of glucose oxidation, as crucial in HCM progression to heart failure. PDK4 represents a promising therapeutic target for preventing or treating heart failure in patients with HCM. Show less

To investigate the genetic etiology of six adult patients with Dilated cardiomyopathy (DCM), and analyze the structure of the identified variants, for providing reference for the diagnosis of DCM. Six adult patients with DCM (patients 1-6) admitted to the Department of Cardiology of Zhumadian Central Hospital from January 2023 to December 2023 were recruited. Clinical data of the patients were retrospectively collected. And 5 mL of peripheral blood was collected from each patient. Pathogenic variants of the patients were detected by whole exome sequencing (WES), and candidate variants were verified by Sanger sequencing. The possible functional significance of the identified missense variants was evaluated using software including SIFT, PolyPhen-2 and Mutation Taster. Specific regions of the MYBPC protein encoded by the MYBPC3 gene from different species were aligned using Mutation Taster. The wild-type and mutant MYBPC proteins were constructed using homologous modeling software MODELLER v10.4 and three-dimensional structures were visualized using PyMOL software. The molecular interaction between MYBPC-C5 domain and myosin with or without the mutation was further analyzed using ZDOCK module in Discovery Studio 2019 software. Pathogenicity ratings for the detected variant sites were performed in accordance with the Standards and Guidelines for the Interpretation of Sequence variants by the American College of Medical Genetics and Genomics (ACMG) (hereafter referred to as the ACMG Guidelines). This study was reviewed and approved by the Ethics Committee of Zhumadian Central Hospital (Approval No. 2022092007). The six DCM patients had typical symptoms of heart failure, and echocardiography showed whole-heart dilation and decreased ventricular wall motion, left ventricular end-diastolic dimension (LVEDD) was 59-74 mm, left ventricular ejection fraction (LVEF) was 35%-43%, and left ventricular fractional shortening (LVFS) was 17%-28%. Variations of the DCM related genes, including a c.98473A>T (p.Lys32825*) variation of the TTN gene and a c.1976T>C (p.Ile659Thr) variation of the MYBPC3 gene, were identified in two patients. Multiple software predicted that both mutations were deleterious. MYBPC3-Ile659Thr mutation affected the highly conserved residue within the C5 domain of MYBPC. Three-dimensional structural analysis of homologous modeling revealed the alterations in amino acid properties and interactions with surrounding amino acids caused by the MYBPC3-Ile659Thr mutation. Further molecular docking analysis showed that the Ile659Thr mutation altered both the hydrogen bond and salt-bridge interactions between the MYBPC-C5 domain and the ligand myosin. Two mutations associated with DCM were identified in this study. The abnormal conformation of the mutant protein further affected its interaction with the ligand myosin, resulting in the phenotype of DCM. Show less

Individuals with diabetes are susceptible to cardiac dysfunction and heart failure, potentially resulting in mortality. Metabolic disorders frequently occur in patients with diabetes, and diabetes usually leads to remodeling of heart structure and cardiac dysfunction. However, the contribution and underlying mechanisms of metabolic and structural coupling in diabetic cardiac dysfunction remain elusive. Two mouse models of type 2 diabetes (T2DM) were used to assess alterations in glucose/lipid metabolism and cardiac structure. The potential metabolic-structural coupling molecule ACBP (acyl-coenzyme A-binding protein) was screened from 4 published datasets of T2DM-associated heart disease. In vivo loss-of-function and gain-of-function approaches were used to investigate the role of ACBP in diabetic cardiac dysfunction. The underlying mechanisms of metabolic and structural coupling were investigated by stable-isotope tracing metabolomics, coimmunoprecipitation coupled with mass spectrometry, and chromatin immunoprecipitation sequencing. Diabetic mouse hearts exhibit enhanced lipid metabolism and impaired ultrastructure with marked cardiac systolic and diastolic dysfunction. Analysis of 4 T2DM public datasets revealed that Our findings demonstrated that ACBP mediates the bidirectional regulation of cardiomyocyte metabolic and structural associations and identified a promising therapeutic target for ameliorating cardiac dysfunction in patients with T2DM. Show less

Sex differences in patients with hypertrophic cardiomyopathy have been elaborated by many studies. However, large studies of the association of patient sex with outcomes after surgical myectomy are scarce. This study evaluated sex disparities in a large Chinese cohort undergoing hypertrophic cardiomyopathy surgery. The cohort encompassed 1613 patients, including 627 (38.9%) women who underwent septal myectomy between 2009 and 2018. At the time of surgery, women were 6 years older and had 1 year longer disease onset-to-surgery delay than men. They were more frequently in New York Heart Association class III/IV and had more severe left ventricular outflow tract obstruction. Compared with men, women had a notably higher left ventricular wall thickness index and a lower extent of late gadolinium enhancement. Women also had more mutations in In patients with obstructive hypertrophic cardiomyopathy, women had a similar fatal outcome but a worse nonfatal outcome than men after surgery. Measures improving quality of life may further enhance the event-free survival of female patients. Close monitoring and follow-up are warranted, especially in younger men and older women. Show less

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation. Show less

Polygonum multiflorum Thunb., a plant rich in diverse bioactive constituents, has been widely used in East Asia in functional foods and medicine to ameliorate inflammatory disorders through its multi-component activity. The effectiveness of these botanical extracts is thought to involve complex interactions among diverse constituents; however, the molecular basis of such interactions remains insufficiently understood. In this study, we explored the anti-inflammatory properties of the ethanol extract of Polygonum multiflorum (PME) through a combination of chemical profiling and computational analysis. PME was found to reduce the production of nitric oxide, inducible nitric oxide synthase, and interleukin-6 in LPS-stimulated RAW 264.7 macrophages. Using HS-SPME-GC-MS in conjunction with network pharmacology, we identified 32 volatile constituents, among which five core compounds were predicted to be associated with three inflammation-related targets: ESR1, FASN, and NR1H3. Dual-ligand molecular docking and molecular dynamics simulations suggested that the sequence of ligand binding may influence the stability and interaction patterns of protein-ligand complexes, offering insights into possible mechanisms of synergy and antagonism mediated by key residues such as ARG394 in ESR1. Overall, these findings contribute to a better understanding of how binding order and structural context may shape constituent-target interactions, providing a basis for the further development of multi-component natural product strategies against inflammation. This study underscores the relevance of incorporating multi-ligand dynamics into natural product research and presents an integrated experimental-computational framework to investigate the cooperative or competitive behaviors of functional food constituents, thereby supporting the rational design of optimized multi-target formulations. Show less

Impaired excretion of lipid deposits within vascular smooth muscle cell-derived foam cells (VSMC-FCs) contributes to the ongoing expansion of the plaque necrotic core. This study aims to explore the effects and underlying mechanisms of exosomes secreted by M2 macrophage (M2-exos) on lipid metabolism of VSMC-FCs and plaque stability. First, immunofluorescence was used to detect the expression levels of CD45 (a recognized differentially-expressed molecule of myeloid and VSMC-FCs) and the key proteins of cholesterol efflux pathway, ABCA1 and ABCG1, in human early and late plaques. Next, an in vitro foam cell model was used to assess the effect and mechanism of M2-exos on lipid metabolism in vascular smooth muscle cells by western blot, Oil red O staining and cell total cholesterol assays. RNA-seq and quantitative real-time PCR were employed to characterize the miRNA profiles within M2-exos. The dual-luciferase reporting system and gene silencing approaches were utilized to assess the regulatory effect of candidate miRNA on target genes and signaling pathways. Subsequently, the effect of M2-exos on plaque progression and stability in ApoE Immunofluorescence revealed that compared to early plaques, VSMC-FCs (CD45 M2-exos exerted an obvious atherosclerotic protective effect, and the underlying mechanism was closely related to MiR-7683-3p, which targeted the 3'UTR of HOXA1 mRNA and activated the PPARγ-LXRα-ABCG1 mediated cholesterol efflux in VSMC-FCs. Show less

To investigate the molecular mechanisms underlying EA(elaidic acid)-induced lipid accumulation in VSMCs(vascular smooth muscle cells). CCK-8 assay determined the effects of EA(0-2.8 mmol/L) on MOVAS(murine aortic vascular smooth muscle cells)to select experimental concentrations. Oil Red O staining combined with quantitative lipid droplet analysis was conducted to examine the effects of EA on intracellular lipid droplet accumulation. Intracellular total cholesterol(TC) and triglyceride(TG) levels were quantified spectrophotometrically to assess EA's effects on intracellular lipid levels. Western blot analyzed protein expression of PPARγ, LXRα, ABCA1, and ABCG1 to delineate EA's pro-foamogenic mechanism. EA dose-dependently suppressed MOVAS viability(P<0.01). EA-treated groups exhibited significant increases in lipid droplet area/number and TC/TG content versus controls(P<0.01). EA downregulated PPARγ and LXRα protein expression(P<0.05), subsequently suppressing downstream targets ABCA1 and ABCG1(P<0.05). EA disrupts lipid metabolism in VSMCs by inhibiting the PPARγ-LXRα-ABCA1/ABCG1 signaling pathway, thereby inducing lipid accumulation and promoting foam cell formation. Show less

Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Fritillariae Thunbergii Bulbus, Leonuri Herba, and Forsythiae Fructus, has shown efficacy in treating cardiovascular diseases, although its mechanisms are unclear. This study aimed to explore the protective effects of QRSJF against atherosclerosis and the mechanisms involved. The composition of QRSJF was analyzed using Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. An 8-week high-fat diet (HFD)-induced atherosclerosis model was established in ApoE Both low- and high-dose QRSJF effectively attenuated dyslipidemia and decreased serum inflammatory cytokine levels in HFD-fed ApoE QRSJF improves dyslipidemia and reduces atherosclerotic plaque in ApoE Show less

Aralia continentalis Kitag roots (ACKRs) have been regarded as a nutritional natural resource for treating different diseases, including type 2 diabetes mellitus (T2DM), and its complications (heart attack; HA, diabetic nephropathy; DN). Nonetheless, an extensive investigation of T2DM-derived complications has yet to be performed. Accordingly, we adopted gas chromatography-mass spectrometry (GC-MS) to identify the molecules of ACKRs, followed by the use of cheminformatics (Similarity Ensemble Approach; SEA, SwissTargetPrediction; STP), bioinformatics (STRING, DisGeNET, and OMIM), and computer screening tools to investigate its corresponding targets, in T2DM diseases and its complications. The primary targets (PPARG, and IL6) were confirmed via a protein-protein interaction (PPI) network, suggesting that IL6- Andrographolide, PPARA-Germacrene D, PPARD- Kaurenoic acid, PPARG- Kaurenoic acid, NR1H3- 1-Naphthalenepropanol, α-ethenyldecahydro-5-(hydroxymethyl)-α,2,5,5,8a-pentamethyl-, and FABP4- Kaurenoic acid conformers on PPAR signaling pathway might exert agonistic mode. These findings underline that ACKRs' bioactives filtered by the devised platform could prevent T2DM-derived complications through multiple-target. Show less

Hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia are interconnected metabolic disorders. This study is designed to characterize how microRNA-206-3p (miR-206) simultaneously prevents de novo lipogenesis (DNL), cholesterol synthesis, and VLDL production in hepatocytes while promoting cholesterol efflux in macrophages. MiR-206 levels were reduced in hepatocytes and macrophages of mice subjected to a high-fat, high-cholesterol diet. A negative feedback between LXRα (liver X receptor alpha) and miR-206 is formed to maintain high LXRα and low miR-206 in hepatocytes. Systemic administration of miR-206 alleviated hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia in mice. A significant reduction in LDL cholesterol and VLDL cholesterol but unaltered HDL cholesterol was observed in miR-206-treated mice. Mirroring these findings, miR-206 reprogrammed the transcriptome of hepatocytes towards the inhibition of DNL, cholesterol synthesis, and assembly and secretion of VLDL. In macrophages, miR-206 activated the expression of genes regulating cholesterol efflux. Hepatocyte-specific expression of miR-206 reduced hepatic and circulating triglycerides and cholesterol, as well as VLDL production, while transplantation of macrophages bearing miR-206 facilitated cholesterol efflux. Mechanistically, miR-206 directly targeted Lxrα and Hmgcr in hepatocytes but facilitated expression of Lxrα in macrophages by targeting macrophage-specific tricho-rhino-phalangeal syndrome 1 (TRPS1), a transcription repressor of Lxrα . By targeting Hmgc r and Lxrα , miR-206 inhibited DNL, VLDL production, and cholesterol synthesis in hepatocytes, whereas it drove cholesterol efflux by activating the TRPS1-LXRα axis. MiR-206, through differentially modulating LXRα signaling in hepatocytes and macrophages, inhibits DNL, promotes cholesterol efflux, and concurrently hinders cholesterol synthesis and VLDL production. MiR-206 simulates the functions of lipid-lowering medications, statins, and LXRα agonists. Show less

While spermatogenesis has been extensively characterized in mammals, its molecular underpinnings in avian species remain largely unexplored. To address this knowledge gap, we performed single-cell transcriptomic profiling of duck testes across developmental stages (10-week immature vs. 23-week mature). Our analysis generated a comprehensive cellular atlas comprising 54,702 cells, resolving eight germ cell clusters (three spermatogonia [SPG], three spermatocytes [SPC], two spermatozoa [SPT]) and nine somatic populations, including peritubular myoid cells, immune subsets (T cells, macrophages, granulocytes), endothelial cells, Leydig cells, and three Sertoli cell subtypes, each defined by unique marker gene signatures. Furthermore, novel marker genes were identified, including EXFABP for granulocyte, ARHGAP15 for T cell regulation, FDX1 specific to Leydig cells (LC), and TSSK3/TSSK2 linked to elongated spermatid formation (SPT). Notably, we identified some novel molecular markers distinguishing these populations. Pseudotemporal trajectory reconstruction of germline development revealed stage-specific enrichment of ribosome, endoplasmic reticulum protein processing, and autophagy pathways. Core regulators MRPL13, MRPL2, MRPL22, MRPS14, MRPS7 (ribosome), HSPA5 (ER stress response), and PIK3C3 (autophagy) emerged as molecular hubs showing progressive downregulation during differentiation. Comparative transcriptomic analysis of germ cells and Sertoli cells between immature (IMT) and mature (MT) testes revealed significant enrichment of the spliceosome pathway in both germ and Sertoli cells. Critical spliceosome components SNRPG, SF3B3, and SNRPF exhibited coordinated downregulation during testicular maturation, suggesting their role as negative regulators of spermatogenic progression. This study establishes the first high-resolution cellular blueprint of avian spermatogenesis, delineating regulatory networks of duck testis cell development. Our findings provide valuable datasets and mechanistic insights into the evolutionary specialization of reproductive strategies in poultry. Show less

Fibromyalgia (FM) is a complex autoimmune disorder characterized by widespread pain and fatigue, with significant diagnostic challenges due to the absence of specific biomarkers. This study aims to identify and validate potential genetic markers for FM to facilitate earlier diagnosis and intervention. We analyzed gene expression data from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) associated with FM. Comprehensive enrichment analyses, including Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathways, were performed to elucidate the biological functions and disease associations of the candidate genes. We used the eXtreme Gradient Boosting (XGBoost) algorithm to develop a diagnostic model, which was validated using independent datasets. Three genes, namely, dual-specificity tyrosine phosphorylation-regulated kinase 3 The study successfully identifies three diagnostic biomarkers for FM, supported by both bioinformatics analysis and machine learning models. These findings could significantly improve diagnostic accuracy for FM, leading to better patient management and treatment outcomes. Show less