To investigate the effects of Qihuang Jianpi Zishen Granules (QJZG) on renal injury in SLE mice, focusing on macrophage M1/M2 polarisation mediated by the AMPK/ULK1 signalling pathway. Parameters of r Show more
To investigate the effects of Qihuang Jianpi Zishen Granules (QJZG) on renal injury in SLE mice, focusing on macrophage M1/M2 polarisation mediated by the AMPK/ULK1 signalling pathway. Parameters of renal function and proteinuria were assessed. Pathological changes in the kidney were examined using H&E, periodic acid-Schiff and Masson's trichrome staining. Serum inflammatory factor levels were quantified using ELISA. The expression levels of the glycolysis rate-limiting enzymes hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) were determined, and the transcriptional levels of AMPK/ULK1 pathway components were measured using quantitative PCR. The abundance of proteins associated with AMPK/ULK1 signalling was assessed via immunoblotting. Flow cytometry was used to quantify CD86+ M1 type and CD206+ M2 type macrophage populations. Dual immunofluorescence staining was employed to visualise F4/80+CD86+ and F4/80+CD206+ coexpression patterns. Compared with the Untreated group, mice in the PRED (prednisone acetate), QJZG and 2-Deoxy-D-glucose groups exhibited improved renal histopathology, reduced levels of creatinine, blood urea nitrogen, 24-hour RRO (24-hour urinary protein), ACR (Albumin-to-Creatinine Ratio), TPCR (Urine Total Protein-to-Creatinine Ratio), tumour necrosis factor alpha, interleukin (IL)-1β, IL-12, IL-23, IL-27, HK2, GLUT1, mTOR, CD86 and iNOS messenger RNA (mRNA), CD86 and iNOS proteins, M1 macrophages, M1/M2 macrophages and F4/80+CD86 expression (p<0.05). They also displayed increased expression of transforming growth factor-beta, IL-4, IL-10, C-C motif chemokine ligand 18, AMPK, ULK1, Atg13, CD206 and Arg-1 mRNA, AMPK, ULK1, CD206 and Arg-1 proteins, M2 macrophages and F4/80+CD206 (p<0.05). QJZG effectively improved renal injury in SLE by reducing inflammation and modulating the AMPK/ULK1 signalling pathway to suppress M1 macrophage polarisation. Show less
Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfuncti Show more
Palmitic acid (PA), being the most prevalent free fatty acid in the human, holds significant implications as a risk factor for atherosclerosis (AS) due to its ability to induce physiological dysfunction in endothelial cells (ECs). Endothelial cell-specific molecule 1 (ESM1), has been identified as a marker for activated ECs. Nevertheless, the mechanisms underlying ESM1-induced endothelial cell proliferation remain elusive. The expression of ESM1, ANGPTL4 and autophagy related protein were confirmed by western blot. Proliferation ability was tested by MTT and EdU. Lipids level was confirmed by Oil red staining. Autophagic flux was confirmed by Monodansylcadaverine (MDC) staining and pCMV-mCherry-GFP-LC3B fluorescence staining assay. The mouse model of AS was used to observe the effect of PA on the ESM1-ANGPTL4-autophagy signaling axis. This study elucidates ESM1-ANGPTL4 axis in maintaining proliferation of ECs and lipid reprogramming. Furthermore, it has been observed that PA has the ability to stimulate EC to autonomously increase the expression of ESM1, which in turn can counteract the detrimental effects of PA on ECs. Conversely, when ESM1 is suppressed, the damaging effects of PA on ECs are exacerbated. Mechanistically, our findings indicate that ESM1 facilitates EC proliferation and lipids homeostasis by up-regulating autophagy through ANGPTL4. This effect of ESM1 on ECs can be attenuated by ATG7 inhibiting. Additionally, the serum levels of ESM1 were found to be elevated in AS mice. ESM1 was found to enhance ECs proliferation and mitigate endothelial cell injury induced by PA through the upregulation of autophagy. This mechanism potentially serves as a protective factor against atherosclerosis progression. Show less
This study aimed to investigate the genetic etiology and clinical features of non-syndromic pediatric obesity in a large Chinese cohort, providing insights into the genetic profile and its correlation Show more
This study aimed to investigate the genetic etiology and clinical features of non-syndromic pediatric obesity in a large Chinese cohort, providing insights into the genetic profile and its correlation with clinical phenotypes. We enrolled 391 children, aged 7-14 years, diagnosed with non-syndromic pediatric obesity at Jiangxi Provincial Children's Hospital from January 2020 to June 2022. Whole-exome sequencing was employed to identify potential genetic causes, focusing on 79 candidate genes associated with obesity. Multivariate logistic regression analysis was performed on the clinical data of the non-syndromic obesity gene-positive group and the gene-negative group. Among the 391 patients, 32 (8.2%) carried 18 non-syndromic obesity genes, with UCP3 and MC4R being the most common. Seven cases (1.8%) were rated as likely pathogenic by the American College of Medical Genetics and Genomics (ACMG). Clinical phenotype and genetic correlation analysis revealed that urinary microalbumin, fT4, GGT, uric acid, serum phosphorus, paternal weight, family history, impaired glucose tolerance (IGT), non-HDL cholesterol (non-HDL-C), and metabolic syndrome (MetS) showed significant statistical differences (P < 0.05). Serum phosphorus is an independent risk factor associated with genetic predispositions to obesity in children and adolescents (P < 0.05). Our findings highlight the genetic heterogeneity of non-syndromic pediatric obesity and identify UCP3 and MC4R as potential hotspot genes in the Chinese population. The study underscores the potential of genetic testing for early diagnosis and personalized management of pediatric obesity. Show less
The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in medi Show more
The development of an immunosuppressive microenvironment is a critical factor in stomach carcinogenesis. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) serve a pivotal function in mediating immune suppression. However, the precise mechanisms underlying PMN-MDSCs infiltration into the tumor immune microenvironment (TIME) and their immunosuppressive functions remain poorly understood. In this investigation, we observed that PMN-MDSCs were up-regulated during stomach carcinogenesis, with gastric cancer (GC) cells secreting CCL26 to promote the infiltration of PMN-MDSCs into the TIME via the CX3CR1 receptor. The infiltrating CX3CR1 Show less
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathologic Show more
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits. Show less
The benefits of plant essential oils (EO) on the health of animals have been frequently reported, but their alteration of lipid metabolism in obese pigs has yet to be explored. This study aimed to ass Show more
The benefits of plant essential oils (EO) on the health of animals have been frequently reported, but their alteration of lipid metabolism in obese pigs has yet to be explored. This study aimed to assess the impact of EO blends (oregano, cinnamon and lemon oils) on growth performance, meat physicochemical parameters, intestinal health and lipid metabolism in the small intestine of weaned Bamei (a kind of obese-type pig) piglets. One hundred and forty-four male 60-day-old weaned Bamei piglets were randomly assigned to three groups of six replicates each: CON (basal diet), T1 (basal diet + 250 mg/kg EO), and T2 (basal diet + 500 mg/kg EO) over 28 days. The results showed that T1 trended to improve the average daily gain and feed intake to body gain ratio (p < 0.1), reduced water loss (p < 0.05), and increased the redness of meat (p < 0.05) compared to the CON. In addition, a significant change in the proportion of C17:0 and C20:1 was observed in the meat of T1 (p < 0.05). Improved intestinal health was evidenced by the reduced crypt depth, improved villi-to-crypt length ratio, and better superoxide dismutase activity in T1 (p < 0.05). Further study on intestinal lipid metabolism showed that duodenal lipase activity and the mRNA expression levels of lipid transport-related genes in the jejunum (FABPs, APOA1, APOB and ACSL3) were significantly reduced, alongside diminished serum lipid metabolites (Total protein and triglyceride) in the groups fed with EO (p < 0.05). In short, EO supplementation especially at 250 mg/kg improved intestinal health and inhibited lipid metabolism, which had a positive effect on the overall performance of Bamei piglets. This new evidence contributes to understanding the early regulatory role of EO in obese pigs and their potential to alleviate adolescent obesity. Show less
This study investigates the relationship between serum homocysteine, blood lipids, and perinatal outcomes in patients with diet-controlled gestational diabetes mellitus (GDM) and those with normal glu Show more
This study investigates the relationship between serum homocysteine, blood lipids, and perinatal outcomes in patients with diet-controlled gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT). A prospective cohort of 150 diet-controlled GDM patients and 150 pregnant women with NGT, all delivering at our hospital, were selected based on predefined criteria. Data on demographics, physical parameters, and perinatal outcomes were compiled. Blood samples for fasting plasma glucose (FPG), homocysteine (Hcy), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and apolipoprotein A1 (apoA1) were collected before delivery. GDM patients exhibited higher levels of FPG, Hcy, and the apoB/apoA1 ratio, but lower HDL-C and apoA1 levels compared to the NGT group. Adverse outcomes such as macrosomia, premature rupture of membranes, and postpartum hemorrhage were more prevalent in the GDM group. In GDM patients, neonatal birth weight positively correlated with FPG and TG levels. Stratified Hcy analysis in GDM showed no significant differences in perinatal outcomes. However, the third quartile of the apoB/apoA1 ratio had a lower incidence of macrosomia compared to the first quartile, and the second quartile showed a higher incidence of birth asphyxia. GDM patients demonstrated increased levels of Hcy, FPG, and the apoB/apoA1 ratio, correlating with more adverse perinatal outcomes than healthy pregnant individuals. The relationships between Hcy, lipids, and these outcomes remain inconclusive, highlighting the need for further research. Show less
This study aims to identify oxidative stress-related genes (OSGs) in papillary thyroid carcinoma (PTC) and their common targets with resveratrol. Oxidative stress-related differentially expressed gene Show more
This study aims to identify oxidative stress-related genes (OSGs) in papillary thyroid carcinoma (PTC) and their common targets with resveratrol. Oxidative stress-related differentially expressed genes (OS-DEGs) were identified by intersecting datasets. The screened core genes were utilized to construct a prognostic model, and their prognostic value, along with their associations with clinical pathological characteristics and immune infiltration, was assessed. Subsequently, the core targets at the intersection of resveratrol and oxidative stress (OS) in PTC were screened, and their binding properties with resveratrol were analyzed. By conducting cross-database analysis, 38 OS-DEGs were identified, and 3 core genes APOE、CDKN2A、APOD were determined. The prognostic model based on core genes exhibited robust prognostic capabilities. The core genes displayed significant correlations with various clinical pathological parameters and a range of immune cells. Additionally, 13 targets of resveratrol for antioxidative stress were screened from databases. 6 high-performing targets, JUN, TGFB1, BCL2, CDKN1A, FOS, ICAM1, were revealed by topological analysis, all exhibiting binding energies lower than - 5.0 kcal/mol. Our study is the pioneering research to provide new insights into the diagnosis, prognosis, and treatment of PTC through the analysis of OSGs, presenting potential clinical implications. Furthermore, this research reveals the molecular functions associated with resveratrol and its pharmacological targets regulating OS in PTC for the first time. Show less
Central nervous system (CNS) tumors often harbor alterations in genes regulating key cellular pathways, including fibroblast growth factor receptor (FGFR) genes. Here, we report the efficacy and safet Show more
Central nervous system (CNS) tumors often harbor alterations in genes regulating key cellular pathways, including fibroblast growth factor receptor (FGFR) genes. Here, we report the efficacy and safety of treatment with pemigatinib, an oral, potent, selective FGFR1-3 inhibitor, in patients with advanced FGFR-altered CNS tumors. FIGHT-207 was a single-arm, open-label, phase 2 study of pemigatinib in patients with advanced solid tumors harboring FGFR fusions/rearrangements or other mutations. Patients received pemigatinib 13.5 mg once daily until disease progression or unacceptable toxicity. Endpoints included tumor response and safety. Of the 13 patients with CNS tumors in FIGHT-207, 10 had glioblastoma. Fibroblast growth factor receptor alterations were FGFR3-TACC3 fusions (n = 9), FGFR1 K656E mutations (n = 2), FGFR1 N546K mutation (n = 1), and FGFR1-MITF fusion (n = 1). Three patients (23%) displayed objective responses (1 complete, 2 partial). Safety was consistent with the overall FIGHT-207 population. Pemigatinib had antitumor activity and a manageable safety profile in patients with CNS tumors. Show less
Heart failure (HF) as the terminal stage of various cardiac diseases, its underlying molecular mechanisms still remain elusive. Emerging evidence have implicated long noncoding RNAs (lncRNAs) play a m Show more
Heart failure (HF) as the terminal stage of various cardiac diseases, its underlying molecular mechanisms still remain elusive. Emerging evidence have implicated long noncoding RNAs (lncRNAs) play a multifaceted role in the progression of cardiac hypertrophy and HF. Here, it is identified that a lncRNA forkhead box O6, opposite strand (Foxo6os) is significantly downregulated in murine HF model induced using transverse aortic constriction (TAC). Knockdown of Foxo6os accelerates cardiomyocyte hypertrophy, reflects as elevated expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and myosin heavy chain 7 (MYH7). Conversely, Foxo6os overexpression can improve cardiac function and alleviate adverse cardiac remodeling. Mechanistically, Foxo6os directly interacts with myosin-binding protein-C (MYBPC3), which then recruits protein kinase C alpha (PKC-α) to facilitate MYBPC3 phosphorylation, resulting in maintaining myocardial contractility and postponing HF progression. Therefore, these findings underscore the critical role of Foxo6os in preserving cardiomyocyte contractile function, suggesting a potential for Foxo6os as a novel therapeutic target of HF. Show less
Gentidelasides A-G (1-7) seven unreported loganin derivatives and fourteen known compounds (8-21) were isolated from the flowers of Gentiana delavayi Franch. Their structures including absolute config Show more
Gentidelasides A-G (1-7) seven unreported loganin derivatives and fourteen known compounds (8-21) were isolated from the flowers of Gentiana delavayi Franch. Their structures including absolute configurations were unambiguously elucidated by analysis of extensive NMR spectroscopy, ECD, and HRESIMS, as well as enzymatic hydrolysis. In vitro bioassay, compound 7 showed obvious inhibitory effects on the production of Aβ40 and Aβ42, with IC Show less
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompl Show more
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompletely defined. Here, we found that BAF60a functions as a chromatin regulator that sustains biphasic GSIS and preserves β cell function under metabolic stress conditions. BAF60a was downregulated in β cells from obese and diabetic mice, monkeys, and humans. β cell-specific inactivation of BAF60a in adult mice impaired GSIS, leading to hyperglycemia and glucose intolerance. Conversely, restoring BAF60a expression improved β cell function and systemic glucose homeostasis. Mechanistically, BAF60a physically interacted with Nkx6.1 to selectively modulate chromatin accessibility and transcriptional activity of target genes critical for GSIS coupling in islet β cells. A BAF60a V278M mutation associated with decreased β cell GSIS function was identified in human donors. Mice carrying this mutation, which disrupted the interaction between BAF60a and Nkx6.1, displayed β cell dysfunction and impaired glucose homeostasis. In addition, GLP-1R and GIPR expression was significantly reduced in BAF60a-deficient islets, attenuating the insulinotropic effect of GLP-1R agonists. Together, these findings support a role for BAF60a as a component of the epigenetic machinery that shapes the chromatin landscape in β cells critical for glucose sensing and insulin secretion. Show less
To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyp Show more
To investigate the impact of obesity on brain structure and cognition using large neuroimaging and genetic data. Associations between body mass index (BMI), gray matter volume (GMV), whiter matter hyper-intensities (WMH), and fluid intelligence score (FIS) were estimated in 30283 participants from the UK Biobank. Longitudinal data analysis was conducted. Genome-wide association studies were applied to explore the genetic loci associations among BMI, GMV, WMH, and FIS. Mendelian Randomization analyses were applied to further estimate the effects of obesity on changes in the brain and cognition. The observational analysis revealed that BMI was negatively associated with GMV (r = -0.15, p < 1 The phenotypic and genetic association between obesity and aging brain and cognitive decline suggested that weight control could be a promising strategy for slowing the aging brain. Show less
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of Show more
Alzheimer's disease (AD) presents significant challenges due to its intricate pathogenic mechanisms and the limited efficacy of single-target therapies. In this study, we investigated the potential of chlorogenic acid (CHA), a multifunctional natural active compound, in AD therapy by developing a trifunctional nanocarrier (MC-H/R/si). CHA was effectively conjugated with iron-based metal-organic frameworks (MIL/Fe-100) through chelation interaction. The resulting nanocomplex (MC) not only enhances the bioavailability of CHA but also facilitates a synergistic antioxidant effect between CHA and MIL/Fe-100. Importantly, CHA can chelate Zn Show less
Lipid overaccumulation in the liver predisposes ducks to metabolic disorders. The molecular mechanism of oleic acid (OA)-induced hepatic steatosis in ducks is not fully elucidated. A cellular model of Show more
Lipid overaccumulation in the liver predisposes ducks to metabolic disorders. The molecular mechanism of oleic acid (OA)-induced hepatic steatosis in ducks is not fully elucidated. A cellular model of steatosis was established by treating primary duck hepatocytes with OA. Transcriptome sequencing was performed to identify key signaling pathways and candidate genes. The role of Apolipoprotein A1 (APOA1) was investigated through overexpression and knockdown experiments. Intracellular triglycerides (TGs) were quantified commercially; lipid droplets were visualized by Oil Red O staining. Intracellular TG accumulation was induced by OA treatment in a dose-dependent manner. Through transcriptome analysis, 1045 differentially expressed genes (DEGs) were identified, with APOA1 being recognized as a key candidate within the peroxisome proliferator-activated receptor (PPAR) signaling pathway. The content of TGs and lipid droplets was increased by APOA1 overexpression, whereas these effects were suppressed by APOA1 knockdown. The expression of acetyl-CoA carboxylase alpha (ACACA) and fatty acid synthase (FASN) was upregulated by APOA1. Conversely, the expression of carnitine O-palmitoyltransferase 1 (CPT1), acyl-CoA oxidase 1 (ACOX1), and apolipoprotein B (APOB) was downregulated. This study demonstrates that OA upregulates APOA1, suggesting the involvement of the PPAR pathway and providing a theoretical basis for modulating hepatic fat deposition. Show less
Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive Show more
Dyslipidemia exacerbates pancreatic β-cell apoptosis, heightening the risk of type 2 diabetes (T2DM). Kansuinine A (KA), a diterpene from Euphorbia roots, exhibits antiapoptotic properties, suggestive of its therapeutic potential against T2DM. In this study, we evaluated the protective effects of KA against apolipoprotein C3 (ApoC3)-rich low-density lipoprotein (LDL) (AC3RL)-induced β-cell apoptosis and its underlying mechanism of action. ApoE Show less
Relying on a single biomarker in biomedical analysis is often insufficient for accurate disease or pathogen determination. A recent trend is using simultaneous multiplex detection of multiple biomarke Show more
Relying on a single biomarker in biomedical analysis is often insufficient for accurate disease or pathogen determination. A recent trend is using simultaneous multiplex detection of multiple biomarkers to improve diagnostic accuracy and throughput. To enable multiplex detection, we developed a series of surface-enhanced Raman scattering (SERS) nanoprobes, referred to as nanoaggregate-embedded beads (NAEBs). These NAEBs were synthesized using three distinct Raman reporter molecules: Safranin O, ethyl violet, and cresyl violet acetate. By integrating the NAEBs with magnetic nanoparticles and a simple capillary magnetofluidic device, we developed a rapid and simultaneous multiplex detection platform for genetic analysis of an aquacultural pathogen Vibrio parahaemolyticus (VP) for pirA, pirB, and ompA and genotyping of Alzheimer's disease's risk factor biomarker Apoliproprotein E (ApoE). For VP detection, a limit of detection (LOD) as low as ~ 10 Show less
Arsenic (As) is a toxic metalloid widespread in the environment, and its exposure has been associated with a variety of adverse health outcomes. As exposure is demonstrated to cause nonalcoholic fatty Show more
Arsenic (As) is a toxic metalloid widespread in the environment, and its exposure has been associated with a variety of adverse health outcomes. As exposure is demonstrated to cause nonalcoholic fatty liver disease (NAFLD), and the underlying epigenetic mechanisms remain largely unknown. This study aimed to investigate the roles of histone modifications in low-level As exposure-induced NAFLD in rats. The results showed that exposure to As caused lipid accumulation and upregulated the expression of lipid metabolism-related genes Show less
Thyroid cancer, the most common endocrine malignancy, is characterized by a unique and complex tumor microenvironment (TME). To unravel the high tumor heterogeneity and molecular mechanisms driving ca Show more
Thyroid cancer, the most common endocrine malignancy, is characterized by a unique and complex tumor microenvironment (TME). To unravel the high tumor heterogeneity and molecular mechanisms driving cancer progression, we performed single-cell RNA sequencing (scRNA-seq) analysis, enabling a comprehensive exploration of cellular diversity and molecular dynamics at single-cell resolution. We employed Principal Component Analysis (PCA) and Uniform Manifold Approximation and Projection (UMAP) for dimensionality reduction and subsequent identification of cellular clusters. Differential gene expression analysis across subclusters was conducted using the FindAllMarkers function, while the DoHeatmap function was utilized to visualize the distribution of differentially expressed genes. The AUCell algorithm was applied to evaluate pathway enrichment within specific cell subtypes. To decipher cellular communication networks, we integrated the CellChat and NicheNet algorithms, which revealed intricate intercellular signaling interactions. Finally, multiplex immunohistochemistry (mIHC) was performed to validate key cellular interactions identified in silico. By analyzing 405,077 single cells from 50 thyroid cancer samples (including papillary, anaplastic, and metastatic tumors) and 14 normal thyroid tissues, we identified four major cellular subpopulations through unbiased clustering based on gene expression patterns and representative cellular markers. The TME was found to encompass diverse immune, endothelial, and mesenchymal cell subtypes, including novel populations such as CD4 + HSPA1A + T cells. Functional pathway enrichment analysis highlighted the roles of abundant cell types in tumor progression. Cell-cell communication analysis uncovered potential immunotherapeutic targets and revealed critical crosstalk among hub niche cells, including APOE+ macrophages, EMT-like cancer-associated fibroblasts (CAFs), and RBP7+ endothelial cells. These findings were further validated by multiplex immunohistochemistry, confirming the spatial organization and interactions of these cell populations within the TME. Our study provides a comprehensive single-cell transcriptomic atlas of thyroid cancer, offering profound insights into tumor heterogeneity, the functional roles of key niche cells, and potential biomarkers for anticancer therapy. These findings not only enhance our understanding of thyroid cancer biology but also pave the way for the development of novel therapeutic strategies targeting the TME. Show less
Inflammatory bowel disease (IBD) is a chronic, immune-mediated intestinal disorder driven by dysregulated immune responses in genetically susceptible individuals. Despite recent advances in treatment, Show more
Inflammatory bowel disease (IBD) is a chronic, immune-mediated intestinal disorder driven by dysregulated immune responses in genetically susceptible individuals. Despite recent advances in treatment, more than 30% of patients either fail to respond initially or lose response over time, underscoring the need for a deeper mechanistic understanding of immunogenetic pathways and the development of individualized therapeutic strategies. We first discuss how newly identified susceptibility genes (e.g., IL23R, NOD2, BDNF, SLC) and their polymorphisms influence immune cell function and epithelial barrier integrity. Single-cell technologies have further revealed novel cell subsets and interactions underlying disease heterogeneity. We then explore the clinical efficacy of classical and emerging targeted therapies, including cytokine-specific biologics, JAK inhibitors, and novel strategies aimed at restoring regulatory T-cell function or blocking integrin-mediated lymphocyte trafficking. Additionally, we highlight promising therapeutic approaches such as fecal microbiota transplantation, microbial metabolite-based interventions, and nanotherapeutics. We further discuss how genetic insights and immune biomarkers can facilitate treatment personalization and improve prognostic stratification. Ultimately, this review emphasizes the transition from broad immunosuppression to precision medicine and proposes integrated approaches-combining multiomics profiling, immune monitoring, and novel therapeutics-to achieve sustained remission and improve long-term outcomes in IBD patients. Show less
Animal models are used widely to study pulmonary hypertension (PH). The cell populations that respond to disease-inducing stimuli in these models and their relationship to human disease remain incompl Show more
Animal models are used widely to study pulmonary hypertension (PH). The cell populations that respond to disease-inducing stimuli in these models and their relationship to human disease remain incompletely defined. This study analyzed the relationship between several rodent models of PH and human disease at single-cell resolution. scRNA-seq was performed on lungs from mice exposed to hypoxia or Sugen/hypoxia, rats exposed to monocrotaline, and controls. A cross-species single-cell dataset was integrated with human lung cell atlas (HLCA) and single-cell dataset from idiopathic pulmonary arterial hypertension (IPAH) to identify overlapping cell subsets between experimental and human disease and species. High levels of overlap were found between species and models of PH, HLCA, and IPAH datasets. Cell subsets perturbed in rat and mouse PH were similar to those found in human disease, with macrophages and endothelial cells being most affected. A novel We established a comprehensive cross-species single-cell atlas of mainstream rodent PH models, highlighting several novel macrophage and endothelial subtypes and signaling motifs potentially contributing to human disease. Show less
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular bacterial pathogen that grows within a specialized membrane-bound compartment known as the Salmonella-containing Show more
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular bacterial pathogen that grows within a specialized membrane-bound compartment known as the Salmonella-containing vacuole (SCV). The molecular composition and regulatory mechanisms governing SCV dynamics remain incompletely understood. In this study, we employed proximity-dependent biotin identification (BioID) to analyze the SCV proteome during infection. For this, we targeted the UltraID biotin ligase to the SCV by fusing it to a type 3 secreted effector. We demonstrate that the bacteria express and translocate the effector-UltraID fusion protein directly into host cells for labeling of the cytosolic face of the SCV surface. Proteomic analysis of biotinylated proteins revealed previously undescribed proteins associated with the SCV, including regulators of vesicular trafficking, cellular metabolism and lipid transport. Among these, VPS13C, a lipid transporter and membrane contact site protein, was identified as a critical regulator of SCV morphology and fission. Functional studies revealed that VPS13C also promotes ER-SCV contact formation, controls SCV positioning in host cells, and facilitates cell-to-cell spread by the bacteria. Together, our findings highlight the utility of BioID as a tool to study host-pathogen interactions in the context of infection and characterize VPS13C as a novel modulator of the intracellular life cycle of S. Typhimurium. Show less
The Huainan pig (HN) is known for its impressive litter size and exquisite meat quality. However, it also exhibits certain drawbacks such as excessive fat deposition, a relatively low percentage of le Show more
The Huainan pig (HN) is known for its impressive litter size and exquisite meat quality. However, it also exhibits certain drawbacks such as excessive fat deposition, a relatively low percentage of lean meat percentage, and a slower growth rate. Crossbreeding with lean-type breeds, such as Large White, Landrace, and Berkshire can enhance offspring traits, and increase genetic diversity. In this study we employed RNA-seq technology to identify differentially expressed genes (DEGs) in subcutaneous adipose tissue (SAT) samples from HN pigs and their crosses with multiple breeds (with three replicates per group). In the SAT of Huainan × Berkshire pigs (BH), Huainan × Yorkshire pigs (YH), and Huainan × Landrace pigs (LH), numerous key functional genes were identified, including In conclusion, these findings offer valuable insights and provide a foundation for future research on the molecular mechanisms underlying fat deposition in pigs. Show less
Mutations in four genes encoding the outer ring complex of nuclear pore complexes (NPCs), NUP85, NUP107, NUP133 and NUP160, cause monogenic steroid-resistant nephrotic syndrome (SRNS). Knockout of NUP Show more
Mutations in four genes encoding the outer ring complex of nuclear pore complexes (NPCs), NUP85, NUP107, NUP133 and NUP160, cause monogenic steroid-resistant nephrotic syndrome (SRNS). Knockout of NUP85, NUP107, or NUP133 in immortalized human podocytes activates CDC42, an important effector of SRNS pathogenesis. However, it is unknown whether or not loss of NUP160 dysregulates CDC42 in the podocytes. Here, we generated a podocyte-specific Nup160 knockout mouse model with double-fluorescent (mT/mG) Cre reporter genes using CRISPR/Cas9 and Cre/loxP technologies. We investigated nephrotic syndrome-associated phenotypes in the Nup160podo-/- mice, and performed single-cell transcriptomic and proteomic analysis of glomerular suspension cells and cultured primary podocytes, respectively. The Nup160podo-/- mice exhibited progressive proteinuria and fusion of podocyte foot processes. We found decreased Cdc42 protein and normal Cdc42 transcriptional level in the podocytes of the Nup160podo-/- mice using analysis of single-cell transcriptomes and proteomes. We subsequently observed that Cdc42 protein decreased in both kidney tissues and cultured primary podocytes of the Nup160podo-/- mice, although Cdc42 mRNA levels were elevated in the cultured primary podocytes of the Nup160podo-/- mice. We also found that Cdc42 activity was significantly reduced in the cultured primary podocytes of the Nup160podo-/- mice. In conclusion, loss of Nup160 dysregulated Cdc42 in the podocytes of the Nup160podo-/- mice with proteinuria and fusion of podocyte foot processes. Our findings suggest that the dysregulation of CDC42 may contribute to the pathogenesis of SRNS in patients with mutations in NUP160. Show less
Qianzhu Jiang, Huiting Li · 2025 · Journal of bioenergetics and biomembranes · Springer · added 2026-04-24
Myocardial fibrosis (MF) is a key pathological process driving heart failure, characterized by excessive extracellular matrix (ECM) deposition and impaired cardiac function. Although myocyte-specific Show more
Myocardial fibrosis (MF) is a key pathological process driving heart failure, characterized by excessive extracellular matrix (ECM) deposition and impaired cardiac function. Although myocyte-specific enhancer factor 2 A (MEF2A) is implicated in cardiac fibroblast activation, its role in MF remains unclear. We manipulated MEF2A expression in cardiac fibroblasts (CFs) through knockdown and overexpression, and assessed fibrosis markers, migration, and RhoA signaling. Binding of MEF2A to the Snail1 promoter was predicted using JASPAR and validated by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. Rescue experiments with Snail1 overexpression and RhoA inhibition were performed. An angiotensin II (Ang II)-induced MF mouse model was used to evaluate cardiac function by echocardiography and to assess collagen deposition through picrosirius red (PSR) staining. MEF2A was significantly upregulated in Ang II-induced fibrotic hearts and CFs. MEF2A knockdown reduced α-SMA and Col1a1 expression, inhibited CF migration, and suppressed activation of the Snail1/RhoA/α-SMA pathway. ChIP and luciferase assays confirmed the direct binding of MEF2A to the Snail1 promoter. Inhibition of RhoA signaling reversed MEF2A-induced myofibroblast activation and migration. Rescue experiments showed that Snail1 overexpression restored the fibrotic phenotype suppressed by MEF2A knockdown. In vivo, MEF2A knockdown improved left ventricular function, reduced collagen deposition (PSR staining), and lowered heart weight/tibia length ratios. MEF2A promotes myocardial fibrosis by directly activating Snail1 and engages the RhoA/α-SMA pathway. Targeting MEF2A offers a promising therapeutic strategy to attenuate MF and improve heart function. Show less
The color of rice leaves are important agronomic traits that directly influence the proportion of sunlight energy utilization and ultimately affect the yield and quality, so it is crucial to excavate Show more
The color of rice leaves are important agronomic traits that directly influence the proportion of sunlight energy utilization and ultimately affect the yield and quality, so it is crucial to excavate the mechanism of regulating rice leave color. To investigate the molecular mechanism that triggers the purple color in rice leaf, phenotypic characterization and genome-wide transcriptome analysis were conducted using the japonica rice cultivar nipponbare (Nip) and its two purple leaf mutants, A total of 2247, 5484, 4525, 2103, 4375 and7029DEGs (differentially expressed genes) were identified in nip-a vs These results not only revealed the molecular mechanism triggering leaf purple color in the rice mutants Show less
Sparstolonin B (SSNB) and Curcumin (Cur), from a pair of compatible herbs, were previously identified as anti-inflammation and T helper 17 (Th17) modulation reagents. However, their compatible roles i Show more
Sparstolonin B (SSNB) and Curcumin (Cur), from a pair of compatible herbs, were previously identified as anti-inflammation and T helper 17 (Th17) modulation reagents. However, their compatible roles in atherosclerosis (AS) and underlying mechanisms remain uninvestigated. In vivo, the apoE The gene-disease interaction and hub gene network reveals Th17-associated genes in the pathogenesis of atherosclerosis. In vitro, SSNB and Cur reduced oxLDL-induced BMDC activation by downregulating CD36. SSNB showed stronger inhibition to inflammatory activation of DC, while Cur more intensively suppressed co-stimulatory molecules. For the Th17/Treg bias in co-culture of BMDC and CD4 Our findings reveal, for the first time, that SSNB and Cur alleviate AS by modulating Th17-stromal cell interactions, with the IL-17RA-TAK1-NF-κB pathway as a related mediator. Notably, SSNB and Cur exhibit distinct anti-atherogenic roles. SSNB primarily targets TLR4/CD36 to inhibit DC activation, Th17 differentiation, VSMC inflammation and mainly inhibited TAK1 phosphorylation, while Cur more significant inhibited macrophage inflammation, and more directly inhibited NF-κB P65 phosphorylation. This study will be valuable for developing novel and precise adjuvant therapies for AS. Show less
Melatonin (MLT) can improve mitophagy, thereby ameliorating cognitive deficits in Alzheimer's disease (AD) patients. Hence, our research focused on the potential value of MLT-related genes (MRGs) in A Show more
Melatonin (MLT) can improve mitophagy, thereby ameliorating cognitive deficits in Alzheimer's disease (AD) patients. Hence, our research focused on the potential value of MLT-related genes (MRGs) in AD through bioinformatic analysis. First, the key cells in the single-cell dataset GSE138852 were screened out based on the proportion of annotated cells and Fisher's test between the AD and control groups. The differentially expressed genes (DEGs) in the key cell and GSE5281 datasets were identified, and the MRGs in GSE5281 were selected via weighted gene coexpression network analysis. After intersecting two sets of DEGs and MRGs, we performed Mendelian randomization analysis to identify the MRGs causally related to AD. Biomarkers were further ascertained through receiver operating characteristic curve (ROC) and expression analysis in GSE5281 and GSE48350. Furthermore, gene set enrichment analysis, immune infiltration analysis and correlation analysis with metabolic pathways were conducted, as well as construction of a regulator network and molecular docking. According to the Fisher test, oligodendrocytes were regarded as key cells due to their excellent abundance in the GSE138852 dataset, in which there were 281 DEGs between the AD and control groups. After overlapping with 3,490 DEGs and 550 MRGs in GSE5281, four genes were found to be causally related to AD, namely, G protein-coupled receptor, family C, group 5, member B (GPRC5B), Methyltransferase-like protein 7 A (METTL7A), NF-κB inhibitor alpha (NFKBIA) and RAS association domain family 4(RASSF4). Moreover, GPRC5B, NFKBIA and RASSF4 were deemed biomarkers, except for METTL7A, because of their indistinctive expression between the AD and control groups. Biomarkers might be involved in oxidative phosphorylation, adipogenesis and heme metabolism. Moreover, T helper type 17 cells, natural killer cells and CD56dim natural killer cells were significantly correlated with biomarkers. Transcription factors (GATA2, POU2F2, NFKB1, etc.) can regulate the expression of biomarkers. Finally, we discovered that all biomarkers could bind to MLT with a strong binding energy. Our study identified three novel biomarkers related to MLT for AD, namely, GPRC5B, NFKBIA and RASSF4, providing a novel approach for the investigation and treatment of AD patients. Show less