The beak bean, found only in waterfowl and Galliformes, aids in foraging, self-defense and pecking hard objects. Its rich coloration results from prolonged evolutionary adaptation. This study analyzed Show more
The beak bean, found only in waterfowl and Galliformes, aids in foraging, self-defense and pecking hard objects. Its rich coloration results from prolonged evolutionary adaptation. This study analyzed beak bean phenotypes of duck at 10, 20, 30 and 40 days of age, revealing that the most common type is the black beak bean, characterized by melanin deposition on the beak surface. This study performed single nucleotide polymorphism (SNP)-based genome-wide association studies (GWASs) to investigate the genetic basis of beak bean color, identifying signals on chromosome 1. The copy number variation region-based GWAS revealed a consistent candidate region overlapping with the SNP-based GWAS signals, further supporting the importance of this genomic region. Locus zoom analysis further refined the candidate regions to 48.5-50.5 and 50.8-52.8 Mb. Functional enrichment analysis highlighted six candidate genes within these regions: KITLG, DUSP6, GALNT4, MGAT4C, ATP2B1 and NTS. Notably, KITLG and DUSP6, which are linked to melanin production, were identified as key candidate genes for beak bean color. Our finding revealed the genetic basis of the bean color traits for the first time in ducks, providing a theoretical foundation and technological framework for enhancing duck beak coloration. Show less
Cancer persists as one of the most formidable global public health crises and socioeconomic burdens of our era, compelling the scientific community to develop innovative and diversified therapeutic mo Show more
Cancer persists as one of the most formidable global public health crises and socioeconomic burdens of our era, compelling the scientific community to develop innovative and diversified therapeutic modalities to revolutionize clinical management and enhance patient outcomes. The recent seminal discovery by Swamynathan et al. has unveiled menadione, a vitamin K precursor, as a potent inducer of triaptosis-a novel regulated cell death pathway mediated through the oxidative modulation of phosphatidylinositol 3-kinase PIK3C3/VPS34. This mechanistically distinct cell death paradigm, characterized by its intimate association with endosomal dysfunction and oxidative stress-induced cellular catastrophe, has demonstrated remarkable therapeutic efficacy in preclinical prostate cancer models, outperforming conventional therapeutic regimens and emerging as a potential paradigm-shifting strategy in oncology. This comprehensive review provides a critical synthesis of the triaptosis discovery landscape, elucidating its molecular intricacies and pathophysiological implications. We systematically examine the multifaceted roles of endosomal biology in oncogenesis and tumor progression, while offering a nuanced perspective on redox homeostasis in malignant cells and the therapeutic potential of oxidative stress modulation. Furthermore, we address the inherent dichotomy of oxidative stress induction in cancer therapy, balancing its therapeutic promise against potential adverse effects. Looking toward the horizon of cancer research, we explore transformative therapeutic strategies leveraging triaptosis induction and its potential applications beyond oncology, aiming to catalyze a new era of precision medicine that ultimately enhances patient survival and quality of life. Show less
Nolan Priedigkeit, Beth Harrison, Robert Shue+27 more · 2025 · Clinical cancer research : an official journal of the American Association for Cancer Research · added 2026-04-24
Inflammatory breast cancer (IBC) is a rare and clinically distinct form of breast cancer associated with poor outcomes. The biological mechanisms driving IBC remain poorly understood, partly due to li Show more
Inflammatory breast cancer (IBC) is a rare and clinically distinct form of breast cancer associated with poor outcomes. The biological mechanisms driving IBC remain poorly understood, partly due to limited large-scale genomic studies that directly compare IBC with non-IBC cases. We conducted a retrospective analysis of 140 patients with IBC (68 primary tumors and 72 metastatic tumors) and 2,317 patients with non-IBC (700 primary tumors, 65 local recurrences, and 1,552 metastases). We compared clinicopathologic features, single-nucleotide variants, copy-number variants, tumor mutational burden, and exploratory survival outcomes between IBC and non-IBC tumors. The most frequent somatic alterations in IBC were detected in TP53 (72%), ERBB2 (32%), PIK3CA (24%), CCND1 (12%), MYC (9%), FGFR1 (8%), and GATA3 (8%). Multivariate logistic regression revealed a significant enrichment of TP53 single-nucleotide variants in IBC, particularly in HER2+ and hormone receptor-positive disease. Tumor mutational burden did not differ between IBC and non-IBC cases. In HER2+ disease, a pathway analysis revealed an enrichment of NOTCH pathway alterations. TP53, CCND1, and RB1 alterations were associated with poor outcomes in IBC. This study provides a comprehensive resource of somatic alterations in a large cohort of patients with metastatic IBC and non-IBC, highlighting genomic features associated with worse outcomes. Our findings reveal a significant enrichment of TP53 mutations, reinforcing its critical role in IBC pathogenesis. Few other distinct differences in IBC were observed, suggesting further investigations-beyond bulk sequencing of the somatic genome-are required to better understand the biology driving this aggressive disease. Show less
Little is known about the importance of blood lipids for risk of myocardial infarction (MI) in Chinese vs. European populations. We compared the associations with MI of apolioprotein B (ApoB) vs. low- Show more
Little is known about the importance of blood lipids for risk of myocardial infarction (MI) in Chinese vs. European populations. We compared the associations with MI of apolioprotein B (ApoB) vs. low-density lipoprotein cholesterol (LDL-C) and remnant-cholesterol (remnant-C) vs. triglycerides in the China Kadoorie Biobank (CKB) and UK Biobank (UKB). Plasma levels of LDL-C, high-density lipoprotein-cholesterol (HDL-C), apolipoprotein B (ApoB), apolipoprotein A1 (ApoA1), non-HDL-C, remnant-C, LDL-C/ApoB, and HDL-C/ApoA1 ratios were measured in a nested case-control study of MI (948 cases, 6101 controls) in CKB and a prospective study (5344 cases in 279 989 participants) in UKB. Associations of lipids with MI were assessed using logistic regression in CKB and Cox regression in UKB after adjustment for confounders and correction for regression dilution. The mean levels of LDL-C were about 30% lower in CKB than in UKB [2.3 (0.6) vs. 3.7 (0.8) mmol/L], but mean levels of HDL-C were comparable [1.3 (0.3) vs. 1.5 (0.4) mmol/L], as were those for triglycerides [1.8 (1.1) vs. 1.7 (1.1) mmol/L]. While the rate ratios (RRs) of MI for 1 SD higher usual levels of LDL-C in Chinese were about half those in Europeans (1.27; 1.13-1.44 vs. 1.55; 1.49-1.61), the corresponding RRs for ApoB or non-HDL with MI were comparable between Chinese and Europeans. The findings reinforce current guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in China that advocate initiation of statin treatment in individuals at high-risk of ASCVD rather than high levels of LDL-C. Show less
Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies worldwide, with cancer stemness and metastasis being critical factors contributing to poor prognosis. While circular R Show more
Colorectal cancer (CRC) remains one of the most prevalent and lethal malignancies worldwide, with cancer stemness and metastasis being critical factors contributing to poor prognosis. While circular RNAs are emerging as important regulators in cancer progression, the role of circGIGYF1 in CRC development is poorly understood. Here, we found that downregulated circGIGYF1 is linked to poor survival rate in CRC patients. circGIGYF1 inhibits CRC stemness, epithelial-mesenchymal transition, and metastatic potential both in vitro and in vivo. Mechanistically, circGIGYF1 promotes the interaction between WWP2 and HOXD13, enhancing HOXD13 ubiquitination and subsequent degradation. This degradation prevented HOXD13 from binding to the CTNNB1 promoter, thereby suppressing Wnt/β-catenin signalling pathway activation. Importantly, circGIGYF1 overexpression or HOXD13 knockdown significantly reduces tumor growth and liver metastasis in mouse models. These findings reveal a circGIGYF1/WWP2/HOXD13/β-catenin regulatory axis in CRC progression and highlight circGIGYF1 as a potential therapeutic target for developing strategies to combat CRC metastasis and recurrence. Show less
The differential diagnosis between Tuberculosis (TB) and Non-tuberculous Mycobacteria (NTM) has historically been constrained by the inadequate sensitivity and specificity of current diagnostic method Show more
The differential diagnosis between Tuberculosis (TB) and Non-tuberculous Mycobacteria (NTM) has historically been constrained by the inadequate sensitivity and specificity of current diagnostic methods. Furthermore, distinguishing between Active Tuberculosis (ATB) and Latent Tuberculosis Infection (LTBI) poses significant challenges. This study aims to develop a molecular differentiation system for ATB, LTBI, and NTM by integrating plasma proteomics with multi-dimensional analytical techniques, while also exploring key biomarkers associated with disease progression and treatment response. Using label-free quantitative technology, we conducted a plasma proteomics analysis across five groups: ATB, LTBI, NTM, Cured Patients (CPs), and Healthy Donors (HD). Differentially Expressed Proteins (DEPs) were identified through screening (FC > 1.5 or <0.67, P < 0.05), followed by Gene Ontology/KEGG pathway enrichment, STRING interaction network, and Mfuzz dynamic clustering analysis to systematically elucidate molecular characteristics. Experimental data were validated through a multidimensional quality control system (Pearson correlation coefficient, peptide distribution, molecular weight distribution, etc.). Enzyme-linked immunosorbent assay (ELISA) was employed to detect the plasma expression levels of target proteins across the groups and to facilitate comparisons. This study identified 1,338 non-redundant proteins across five cohorts. Comparative analysis revealed 142 DEPs across the three comparative groups (ATB, LTBI, and NTM), which were primarily localized in the extracellular domain. Key findings include: 27 DEPs in the ATB-LTBI group, primarily enriched in inflammatory responses (such as A2M, IL-1R2) and epithelial barrier functions (TGM3, KRT3); 69 DEPs in the ATB-NTM group, characterized by significant changes in immunoglobulin light chains (IGLV2-11) and innate immune effector molecules (S100A8); 46 DEPs in the NTM-LTBI group, closely related to lipid metabolism (APOC3) and extracellular matrix remodeling (FN1). KEGG pathway analysis revealed that DEPs in the ATB-LTBI group were enriched in nitrogen metabolism pathways, those in the ATB-NTM group were associated with thyroid hormone synthesis, and the NTM-LTBI group was involved in phagosome function. Dynamic clustering results showed six treatment response modules: Cluster 1/2 (riboflavin metabolism, complement coagulation pathway) were activated post-treatment, Cluster 3/4 (proteasome, cardiac signaling pathway) exhibited partial reversal in expression, and Cluster 5/6 (platelet activation, cytoskeleton) showed delayed regression. Research confirmed 10 differential proteins between the ATB-CPs and ATB-HD groups, including S100A8, LTA4H, and DEFA1B, which constitute a molecular fingerprint specific to ATB. ELISA validation confirmed significantly elevated S100A8 and GPX3 in ATB group, while NTM group showed higher FGB and lower ATRN levels. This study systematically reveals the plasma proteomic characteristics under infection statuses caused by different mycobacteria. A discrimination framework for ATB/LTBI/NTM was constructed based on disease-specific differential proteins, overcoming the limitations of traditional diagnostic techniques in distinguishing infection states. Through dynamic analysis of six temporal therapeutic modules, the reprogramming patterns of the host protein network during tuberculosis treatment were elucidated. This research lays a multidimensional molecular foundation for the precise typing, personalized treatment, and prognostic evaluation of mycobacterial infections. Show less
Metabolic dysfunction-associated fatty liver disease (MAFLD), driven by dyslipidemia and hepatic lipid deposition, has become a major public health concern. Angiopoietin-like protein 3 (ANGPTL3), a li Show more
Metabolic dysfunction-associated fatty liver disease (MAFLD), driven by dyslipidemia and hepatic lipid deposition, has become a major public health concern. Angiopoietin-like protein 3 (ANGPTL3), a lipoprotein lipase (LPL) activity inhibitor, can inhibit triglycerides (TGs) decomposition, and fibroblast growth factor 21 (FGF21) enhances fatty acids' β-oxidation in liver. We constructed a novel fusion protein combining the anti-ANGPTL3 nanobody FD03 and FGF21 (FD03-FGF21), which exerted appropriate binding affinities to ANGPTL3 and β-Klotho respectively. Our results showed FD03-FGF21 restored bioactivity of LPL which inhibited by ANGPTL3 and activated downstream pathway of FGF21 in iLite FGF21 assay-ready cells. Next, FD03-FGF21 showed a significant therapeutic effect in MAFLD mice, including attenuation of metabolic dyslipidemia, hepatic lipid accumulation, and impaired glucose tolerance. Compared to other treatments, FD03-FGF21 achieved the most significant therapeutic effect with a 79.78 % attenuation of low-density lipoprotein cholesterol (LDL-C) and a 95.8 % reduction of hepatic lipid accumulation. Mechanistically, transcriptomic analysis revealed that differential expression genes (DEGs) were principally clustered into lipid metabolism and oxidative stress pathways after the fusion protein treatment, especially the key lipid metabolism genes of LDLR and CD36 were significantly upregulated and downregulated respectively, as confirmed by WB. Furthermore, lipidomic and metabolomic analysis indicated the fusion protein ameliorated disorders in lipid and protein metabolism mainly through the downregulation of DG and upregulation of PC. Hepatic oxidative stress and inflammation were significantly reduced after administration of the fusion protein in MAFLD mice. Collectively, FD03-FGF21 represents an effective therapeutic strategy for MAFLD therapy through ameliorating lipid metabolism and oxidative stress. Show less
Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation and We conducted a clinicopathological Show more
Calcified chondroid mesenchymal neoplasm (CCMN) is a recently identified category of soft tissue neoplasms defined by cartilage or cartilaginous matrix formation and We conducted a clinicopathological analysis of five newly identified CCMN cases and reviewed 87 cases documented in PubMed. Next-generation sequencing was used to detect molecular alterations, while clinical, radiological and histopathological features were extensively reviewed. CCMN typically affects adults, presenting as a slow-growing, painless mass in soft tissue. Histologically, CCMN exhibits a chondroid matrix with variable calcification. Molecular analyses in our cases identified CCMN should be considered in the differential diagnosis of soft tissue tumours with chondroid and calcified components. Detecting Show less
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatment Show more
To explore the optimal row-ratio in mechanized hybrid rice seed production, a field experiment was conducted in 2024 at Qionglai and Mianzhu using 'Tiantai A' × 'Taihui 808'. Three row-ratio treatments (H1: 18:6, H2: 24:6, and H3: 30:6) were tested using agricultural unmanned aerial vehicles (AUAVs) for pollination assistance. The results showed that row-ratio had little effect on sterile line flowering dynamics. The index of flowers meeting (IFM) was 0.71-0.72 at Qionglai and 0.81-0.86 at Mianzhu, with 11 to 12 days of flowering duration. As the row-ratio increased, total pollen quantity in the panicle layer and grain filling rate (GFR) decreased, while grain infection rate (GIR) increased. The responses of grain blighted rate (GBR), grain empty rate (GER), and fertilization success rate (FSR) to row-ratio varied between sites. Pollen density and GFR followed the pattern of near region (NR) > central region (CR) > far region (FR). Within the panicle, pollen density was generally highest in the upper panicle layer (UPL), followed by the middle (MPL) and lower (LPL) layers, with partial exceptions observed in the H2 and H3 treatments at Mianzhu. The vertical distribution of GFR varied by site: at Qionglai, it was apical parts of panicle (APP) > median parts (MPP) > basal parts (BPP), whereas at Mianzhu the order was MPP > APP > BPP. With wider row-ratios, yield per unit area (YUA) and GFR declined (H1 > H2 > H3), while 1,000-grain weight increased or decreased and then increased. Under H1, yields reached 2,107.50 kg ha Show less
Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. The Show more
Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement. We developed an oversized AAV vector as a gene therapy to treat Show less
Evidence has linked self-reported sedentary behaviors with dementia and cognitive impairment; however, the underlying mechanisms remain poorly understood. We investigated the associations of accelerom Show more
Evidence has linked self-reported sedentary behaviors with dementia and cognitive impairment; however, the underlying mechanisms remain poorly understood. We investigated the associations of accelerometer-measured sedentary behavior patterns with gray matter atrophy patterns in rural-dwelling older adults, while taking into account the manner in which sedentary time is accrued (in short or long bouts). This community-based study involved 911 dementia-free older adults (age ≥ 60 years, 59% women) who participated in both ActiGraph and brain MRI substudies within MIND-China (2018-2020). Sedentary behavior parameters (total sedentary time, mean sedentary bout duration, and sedentary breaks) were recorded with accelerometers. Regional gray matter volumes (GMV) were measured using voxel-based morphometry (VBM) methods. Data were analyzed using the general linear regression models, restricted cubic spline curves, and VBM analysis. There was an inverted U-shaped association between daily sedentary time and GMV in temporal, cingulate, and medial temporal cortex, while longer mean sedentary bout duration was linearly related to decreased GMV in total, frontal, temporal, insula, cingulate, and medial temporal cortex. Greater daily time spent in light or moderate-to-vigorous physical activity (LPA and MVPA) was correlated with larger insula GMV. The VBM analysis suggested that prolonged daily total sedentary time and mean sedentary bout duration were significantly associated with smaller GMV in extensive brain regions, especially in thalamus and insula. In conclusion, gray matter atrophy associated with sedentary behavior in older adults is characterized by reduced GMV in global, frontal, temporal, medial temporal, and cingulate cortex, especially in the insula and thalamus regions. Show less
Yu-Xuan Peng, Hong-Zheng Li, Wen-Wen Yang+4 more · 2025 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
This study aims to investigate the anti-atherosclerotic mechanism of Maiguan Fukang Tablets(MGFK) by integrating ultra-high-performance liquid chromatography-quadrupole orbitrap mass spectrometry(UHPL Show more
This study aims to investigate the anti-atherosclerotic mechanism of Maiguan Fukang Tablets(MGFK) by integrating ultra-high-performance liquid chromatography-quadrupole orbitrap mass spectrometry(UHPLC-QE-MS), network pharmacology, and animal experiments. UHPLC-QE-MS identified 131 compounds in MGFK. Network pharmacology databases were utilized to retrieve drug targets and disease-related targets, and a "component-target-disease" network was constructed, yielding 418 overlapping potential therapeutic targets. These targets were further analyzed via protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, which revealed significant associations primarily with inflammatory response, negative regulation of apoptotic process, and the phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT) signaling pathway. Molecular docking demonstrated strong binding affinities between protein kinase B1(AKT1) and core active compounds including luteolin, liquiritigenin, apigenin, and kaempferol. An atherosclerosis(AS) model was established in ApoE~(-/-) mice by feeding a high-fat diet for 14 weeks, and mice were randomly divided into a model group, MGFK high-dose group, MGFK low-dose group, and atorvastatin group. Experimental results confirmed that MGFK significantly reduced aortic plaque area, decreased lipid and foam cell proportion within plaques, lowered serum total cholesterol(TC), and reduced the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and IL-6. Furthermore, MGFK decreased the apoptosis rate within plaques, upregulated B-cell lymphoma-2(BCL-2) expression, downregulated BCL-2-associated X protein(BAX) and cleaved caspase-3, and promoted the phosphorylation of PI3K and AKT. These findings suggest that MGFK exerts anti-atherosclerotic effects potentially by regulating the PI3K/AKT signaling pathway, thereby reducing apoptosis within plaques, lowering levels of inflammatory cytokines and blood lipids, and attenuating plaque size, lipid content, and foam cell formation. Show less
Women with autoimmune diseases (AIDs) experience chronic immune dysregulation and hormonal fluctuations, both of which may influence breast cancer risk. However, it remains unclear whether this risk i Show more
Women with autoimmune diseases (AIDs) experience chronic immune dysregulation and hormonal fluctuations, both of which may influence breast cancer risk. However, it remains unclear whether this risk is driven mainly by its treatment or the underlying disease, highlighting the need for integrating real-world data and genetic evidence. The FDA Adverse Event Reporting System (FAERS) were utilized to identify breast cancer safety signals among women with AIDs, analyzing 11,479 reports from 2004 to 2024. Disproportionality analyses using Reporting Odds Ratio (ROR) and Information Component (IC) were conducted. Then, we mapped these drugs to their target genes and performed mendelian randomization (MR) to assess their causal relationships with breast cancer. Finally, we investigated shared genetic architecture between breast cancer and AIDs using global and local genetic correlation, cross-trait meta-analysis, and transcriptome-wide association studies. We identified 13 immunosuppressive drugs (TNF inhibitors, interleukin inhibitors, and monoclonal antibodies), 3 immunostimulants and 16 adjunctive drugs associated with increased breast cancer reporting in patients with AIDs. The drugs with the highest case reports for positive disproportionality analysis were interferon beta-1a (N: 1731, IC [IC025] 1.56 [1.49]), natalizumab (798, 0.65 [0.54]), and infliximab (741, 0.64 [0.53]). MR results revealed causal links between 9 drug targets and breast cancer risk, such as FDPS (OR: 0.66, p: 1.33E-08), CALCRL (OR: 0.887, p: 4.77E-06) and PARP1 (OR: 1.051, p: 3.50E-06). Global genetic correlation identified significant shared heritability between breast cancer and 3 specific AIDs, including type 1 diabetes mellitus (rg: -0.242, p: 0.95E-4), ulcerative colitis (rg: 0.125, p: 0.29E-2), and migraine (rg: 0.078, p: 0.79E-2). Specifically, the most notable genetic overlap was observed between breast cancer and type 1 diabetes mellitus, with significant shared risk SNPs (rs12046289 and rs6679677) and susceptibility genes (ADCY3 and CENPO). Our study uncovered several immune-related drugs associated with increased breast cancer reporting in women with AIDs. This risk may be explained by several potential drug targets with causal roles, or by the shared genetic comorbidity between specific AIDs and breast cancer. These insights emphasize the need for tailored breast cancer surveillance and highlight potential molecular targets for intervention in vulnerable populations. Show less
A meta-analysis was conducted to assess the effects of citric acid (CA) on silage fermentation, and then used whole-plant cassava silage as a model to explore the underlying microbiological mechanisms Show more
A meta-analysis was conducted to assess the effects of citric acid (CA) on silage fermentation, and then used whole-plant cassava silage as a model to explore the underlying microbiological mechanisms with metagenomic and metabolomic data. The meta-analysis revealed that CA supplementation increased the dry matter, crude protein, water-soluble carbohydrate, and lactic acid contents in silage, but decreased the pH, dry matter loss, and the contents of fiber, NH Show less
Alzheimer's disease (AD), a neurodegenerative disorder with complex etiologies, manifests through a cascade of pathological changes before clinical symptoms become apparent. Among these early changes, Show more
Alzheimer's disease (AD), a neurodegenerative disorder with complex etiologies, manifests through a cascade of pathological changes before clinical symptoms become apparent. Among these early changes, alterations in the expression of non-coding RNAs (ncRNAs) have emerged as pivotal events. In this study, we focused on the aberrant expression of ncRNAs and revealed that Lamr1-ps1, a pseudogene of the laminin receptor, significantly exacerbates early spatial learning and memory deficits in APP/PS1 mice. Through a combination of bioinformatics prediction and experimental validation, we identified the miR-29c/Bace1 pathway as a potential regulatory mechanism by which Lamr1-ps1 influences AD pathology. Importantly, augmenting the miR-29c-3p levels in mice ameliorated memory deficits, underscoring the therapeutic potential of targeting miR-29c-3p in early AD intervention. This study not only provides new insights into the role of pseudogenes in AD but also consolidates a foundational basis for considering miR-29c as a viable therapeutic target, offering a novel avenue for AD research and treatment strategies. Show less
The incidence of silent myocardial infarction (SMI) is increasing. Meanwhile, due to the atypical clinical symptoms and signs associated with SMI, the prognosis for patients is often poor. This predic Show more
The incidence of silent myocardial infarction (SMI) is increasing. Meanwhile, due to the atypical clinical symptoms and signs associated with SMI, the prognosis for patients is often poor. This prediction model used the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analyses to screen variables. Predictive accuracy was assessed using the area under the receiver operating characteristic (ROC) curve (AUC). The clinical decision curve analysis (DCA), alongside the calibration curve and clinical impact curve (CIC) analyses, were used to assess model validity. This study included 174 patients, 64 (36.8%) of whom experienced SMI; logistic regression analysis identified six variables: gender, age, high-density lipoprotein cholesterol (HDL-C), apolipoprotein B/apolipoprotein A1 (ApoB/A1), uric acid (UA), and triglyceride glucose-body mass index (TyG-BMI). The results identified the TyG-BMI as a predictor of SMI (odds ratios (OR) = 1.02, 95% CI: 1.01-1.03; The TyG-BMI is an independent predictor of SMI. A prediction model based on the TyG-BMI showed good predictive ability for SMI. Show less
Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of canc Show more
Metastatic spread of cancer is the leading cause of death in patients with epithelial ovarian cancer (EOC), and elucidation of the molecular mechanisms underlying this process is a major focus of cancer research. Fibroblast growth factor-inducible 14 (Fn14) has been shown to regulate wound repair, inflammation, angiogenesis, and chemoresistance, but its functional role in metastasis in EOC is still unknown. Here it is reported that Fn14 is identified as a cancer metastasis suppressor that inhibits the migratory and invasive potential of EOC cells by down-regulating epithelial-mesenchymal transition (EMT). Mechanistically, it is identified that Fn14 promotes acetylation-dependent protein degradation of Slug, a key transcriptional factor associated with EMT. The deacetylase Sirtuin 2 (SIRT2) has been reported to be involved in the deacetylation of Slug protein to stabilize it and then prevent its degradation in the nucleus. The results showed that Fn14 alters the subcellular localization of (SIRT2) by interacting with SIRT2, leading to reduced SIRT2 shuttling into the nucleus and subsequently promoting the acetylated degradation of Slug. Collectively, the work has demonstrated for the first time that Fn14 inhibits EOC metastasis by regulating SIRT2-mediated Slug deacetylation, providing a new perspective and method for the development of future novel therapeutic strategies for the treatment of EOC metastasis. Show less
Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent type of heart failure, but effective treatments are lacking. Cardiac lymphatics play a crucial role in maintaining Show more
Heart failure with preserved ejection fraction (HFpEF) has become the most prevalent type of heart failure, but effective treatments are lacking. Cardiac lymphatics play a crucial role in maintaining heart health by draining fluids and immune cells. However, their involvement in HFpEF remains largely unexplored. We examined cardiac lymphatic alterations in mice with HFpEF with comorbid obesity and hypertension, and in heart tissues from patients with HFpEF. Using genetically engineered mouse models and various cellular and molecular techniques, we investigated the role of cardiac lymphatics in HFpEF and the underlying mechanisms. In mice with HFpEF, cardiac lymphatics displayed substantial structural and functional anomalies, including decreased lymphatic endothelial cell (LEC) density, vessel fragmentation, reduced branch connections, and impaired capacity to drain fluids and immune cells. LEC numbers and marker expression levels were also decreased in heart tissues from patients with HFpEF. Stimulating lymphangiogenesis with an adeno-associated virus expressing an engineered variant of vascular endothelial growth factor C (VEGFC Our study provides evidence that cardiac lymphatic disruption, driven by impaired BCAA catabolism in LECs, is a key factor contributing to HFpEF. These findings unravel the crucial role of BCAA catabolism in modulating lymphatic biology, and suggest that preserving cardiac lymphatic integrity may present a novel therapeutic strategy for HFpEF. Show less
β-Hydroxybutyrylation (Kbhb) modification regulates protein molecular fates in either physiology or pathology, including cancer. However, the function and regulatory mechanism of Kbhb remain completel Show more
β-Hydroxybutyrylation (Kbhb) modification regulates protein molecular fates in either physiology or pathology, including cancer. However, the function and regulatory mechanism of Kbhb remain completely unknown in cancer metastasis. Here, we report that β-hydroxybutyrate (BHB) is clinically associated with the progression of pancreatic cancer and functionally promotes pancreatic cancer cell metastasis. Mechanistically, BHB induces Kbhb modification of Snail at lysine 152 to enhance Snail stabilization, which is regulated by Kbhb modification enzyme CREB-binding protein (CBP), and subsequently prevents Snail degradation by blocking recognition of E3 ubiquitin ligases FBXL14. Furthermore, either targeting Snail Kbhb modification or CBP inhibitor decreases cancer metastasis and enhances the therapeutic efficacy of gemcitabine in pancreatic cancer cells. Collectively, our study reveals that Kbhb of Snail is critical to promote metastasis and provides a potential therapeutic strategy. Show less
To construct a nomogram for predicting metabolic syndrome (MetS) in women with polycystic ovary syndrome. In this retrospective study, we analyzed clinical and biochemical data from 859 Chinese women Show more
To construct a nomogram for predicting metabolic syndrome (MetS) in women with polycystic ovary syndrome. In this retrospective study, we analyzed clinical and biochemical data from 859 Chinese women diagnosed with PCOS. Univariable logistic regression and forward stepwise logistic regression were employed to identify independent predictors of MetS. A predictive nomogram was developed that integrates age, acne status, body mass index (BMI), fasting insulin levels (FINS), and the ApoB/ApoA ratio. The model's discriminative performance, calibration accuracy, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration curves accompanied by Brier scores, Hosmer - Lemeshow tests, decision curve analysis (DCA), and clinical impact curves (CIC). Internal validation was conducted through bootstrap resampling over 1,000 iterations. The nomogram exhibited strong discriminative capability with an AUC of 0.874 (95% CI: 0.850-0.899), surpassing BMI alone which had an AUC of 0.824 ( The proposed nomogram accurately predicts MetS risk in PCOS patients, supporting early identification and individualized management. Show less
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein in Show more
The highly organized structures of the immunological synapse (IS) are crucial for T cell activation. PDZ domains might be involved in the formation of the IS by serving as docking sites for protein interactions. In this study, we investigate the role of the PALS1-associated tight junction protein (PATJ), which contains 10 PDZ domains, in the formation of IS and its subsequent impact on T cell activation. To elucidate the function of PATJ, we generated murine models with conditional T cell-specific knockout of We observed a rapid increase in PATJ expression during T cell activation. Conditional knockout of Our study reveals an important role of PATJ in the formation of IS and provides an approach to improve the efficacy of CAR-T therapy. Show less
Mengru Pan, Yifan Qian, Linlin Jiang+2 more · 2025 · Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology · Taylor & Francis · added 2026-04-24
To assess the potential therapeutic effects of glucose-dependent insulinotropic peptide (GIP) on hyperandrogenism. Polycystic ovary syndrome (PCOS) mouse models induced by dehydroepiandrosterone (DHEA Show more
To assess the potential therapeutic effects of glucose-dependent insulinotropic peptide (GIP) on hyperandrogenism. Polycystic ovary syndrome (PCOS) mouse models induced by dehydroepiandrosterone (DHEA) were established to evaluate the impact of GIP on androgen synthesis Administration of GIP significantly reduced testosterone secretion in a DHEA-induced PCOS mouse model. Consistent with these findings, GIP treatment decreased testosterone release and downregulated the expression of GIP receptor (GIPR), steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1), and cytochrome P450 family 17 subfamily A member 1 (CYP17A1) in NCI-H295R cells. Notably, RNA-seq revealed that Our study demonstrated that the administration of GIP reduces androgen synthesis in PCOS mouse models and at the cellular level, suggesting its potential as a novel therapeutic target for managing PCOS. Show less
Deep brain stimulation (DBS) has emerged as a prospective treatment for psychiatric disorders; for example, DBS targeting the nucleus accumbens (NAc) abolishes addictive behaviors. However, neither th Show more
Deep brain stimulation (DBS) has emerged as a prospective treatment for psychiatric disorders; for example, DBS targeting the nucleus accumbens (NAc) abolishes addictive behaviors. However, neither the core pathway nor the cellular mechanisms underlying these therapeutic effects are known. Here, morphine-induced conditioned place preference (CPP) in mice as an addiction model and NAc-DBS combined with adeno-associated virus gene delivery for activity-dependent tagging, transgenic and chemogenetic manipulation of recruited neuronal networks are used. It is reported that a cortical-accumbal pathway and local fibroblast growth factor 1 (FGF1) signaling in the medial prefrontal cortex (mPFC) are critical for NAc-DBS to be effective in altering morphine CPP. It is shown that NAc-DBS retrogradely activates mPFC neurons projecting to the NAc, and chemogenetic activation/inhibition of these DBS-activated neuron ensembles in the mPFC reproduces the NAc-DBS effects on CPP. Sustained therapeutic effects accompany reductions in local FGF1 binding to fibroblast growth factor receptor 1 (FGFR1) in these neurons. Additionally, overexpressing FGF1 in the mPFC-NAc pathway abolishes the therapeutic effects of NAc-DBS. These results demonstrate that the mPFC-NAc pathway forms a top-down motif to regulate the therapeutic effects of subcortical DBS on addiction. These results support the potential for addiction treatments involving FGF1 signaling and highlight the mPFC as a target for noninvasive brain stimulation. Show less
Although the human cerebellum is known to be neuropathologically impaired in Alzheimer's disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes tha Show more
Although the human cerebellum is known to be neuropathologically impaired in Alzheimer's disease (AD) and AD-related dementias (ADRD), the cell type-specific transcriptional and epigenomic changes that contribute to this pathology are not well understood. Here, we report single-nucleus multiome (snRNA-seq and snATAC-seq) analysis of 103,861 nuclei isolated from both cerebellum and frontal cortex of AD/ADRD patients and normal controls. Using peak-to-gene linkage analysis, we identified 431,834 significant linkages between gene expression and cell subtype-specific chromatin accessibility regions enriched for candidate cis-regulatory elements (cCREs). These cCREs were associated with AD/ADRD-specific transcriptomic changes and disease-related gene regulatory networks, especially for RAR Related Orphan Receptor A (RORA) and E74 Like ETS Transcription Factor 1 (ELF1) in cerebellar Purkinje cells and granule cells, respectively. Trajectory analysis of granule cell populations further identified disease-relevant transcription factors, such as RORA, and their regulatory targets. Finally, we pinpointed two likely causal genes, Seizure Related 6 Homolog Like 2 (SEZ6L2) in Purkinje cells and KAT8 Regulatory NSL Complex Subunit 1 (KANSL1) in granule cells, through integrative analysis of cCREs derived from snATAC-seq, genome-wide AD/ADRD loci, and three-dimensional (3D) genome data. Via CRISPRi experiments, we found that perturbation of rs4788201 and rs62056801 significantly inhibited the expression of their target genes, SEZ6L2 and KANSL1, in human iPSC-derived neurons. This cell subtype-specific regulatory landscape in the human cerebellum identified here offers novel genomic and epigenomic insights into the neuropathology and pathobiology of AD/ADRD and other neurological disorders if broadly applied. Show less
Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile toward a synthetic phenotype plays a critical role in atherosclerosis. Although the redox-sensitive sentrin/Small Ubiqui Show more
Phenotypic switching of vascular smooth muscle cells (VSMCs) from a contractile toward a synthetic phenotype plays a critical role in atherosclerosis. Although the redox-sensitive sentrin/Small Ubiquitin-like Modifier (SUMO)-specific protease 3 (SENP3), which preferentially deconjugates SUMO2/3, has been linked to oxidative stress, its role in atherosclerosis remains poorly defined. In this study, we demonstrate that SENP3 is significantly upregulated in human and mouse atherosclerotic lesions and in VSMCs exposed to pro-atherogenic stimuli. Using smooth muscle-specific Senp3 knockout mice (ApoE Show less
Yan Huang, Bo-Wen Yue, Yue-Qin Hu+5 more · 2025 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mec Show more
Anxiety disorder is a highly prevalent psychological illness, and research has shown that obesity is a significant risk factor for its development. This study explored the ameliorative effects and mechanisms of saponins from Panax japonicus(SPJ) on anxiety disorder in mice fed a high-fat diet(HFD). Fifty C57BL/6J mice were randomly divided into normal control diet(NCD) group, HFD group, and low-and high-dose SPJ groups. At week 12, six mice from the HFD group were further divided into a control group(treated with DMSO) and an exogenous fibroblast growth factor 21(FGF21) group(administered rFGF21). The anxiety-like behavior of the mice was assessed using the open field test and elevated plus maze test. Hematoxylin-eosin(HE) staining and oil red O staining were performed to observe pathological changes in the liver and adipose tissue. Glucose metabolism was evaluated through the glucose tolerance test(GTT) and insulin tolerance test(ITT). Western blot analysis was performed to detect the expression of FGF21 and its downstream-related proteins in the liver and cortex, along with the expression of brain-derived neurotrophic factor(BDNF), disks large homolog 4(DLG4), and synaptophysin(SYP) in the cortex. Real-time quantitative fluorescent PCR(qPCR) was used to detect the expression of FGF21 and its receptor genes in the liver and cortex. Immunofluorescence staining was employed to examine the expression of neuronal activator c-Fos, FGF21, and the FGF21 co-receptor β-klotho in the cerebral cortex. The results showed that SPJ significantly improved the frequency of activity in the open arms of the elevated plus maze and the central area of the open field in HFD mice, up-regulated the expression of BDNF, DLG4, and SYP, and effectively alleviated anxiety-like behaviors in HFD mice. Compared with the NCD group, HFD mice exhibited up-regulated expression of FGF21 in the liver and cerebral cortex, while the expression of fibroblast growth factor receptor 1(FGFR1) and β-klotho was significantly down-regulated, suggesting that HFD mice exhibited FGF21 resistance. SPJ markedly up-regulated the β-klotho levels in HFD mice, reversing FGF21 resistance. Further comparison with exogenously administered FGF21 revealed that SPJ activates brain cortical regions in a consistent manner, and additionally, SPJ promotes the number and colocalization of c-Fos and β-klotho positive cells in the brain cortex. In summary, SPJ effectively alleviates anxiety-like behaviors in HFD mice. Its mechanism is associated with up-regulation of β-klotho expression in the brain, reversal of FGF21 resistance, and subsequent activation of neurons in the cerebral cortex and amygdala. Show less
Atherosclerosis (AS) remains a leading cause of cardiovascular morbidity and mortality, characterized by intricate interactions between immune dysregulation and lipid metabolism abnormalities-identify Show more
Atherosclerosis (AS) remains a leading cause of cardiovascular morbidity and mortality, characterized by intricate interactions between immune dysregulation and lipid metabolism abnormalities-identifying key mediators in its pathogenesis is critical for improving diagnostics and therapies. This study focuses on Transmembrane Protein 106A (TMEM106A) to clarify its role and clinical relevance in AS progression. Public transcriptomic datasets (GSE43292, GSE100927, GSE28829) were analyzed to assess TMEM106A expression and diagnostic value; single-cell RNA-seq data (GSE159677) defined its cellular localization. Immune infiltration (ssGSEA, Cibersort, xCell) and CellChat (intercellular communication) analyses explored its immune associations. TMEM106A was significantly upregulated in AS samples across datasets, with strong diagnostic efficacy (AUC 0.80-0.95). Single-cell analysis confirmed its specific enrichment in macrophages, with functional links to immune-related pathways. TMEM106A promoted macrophage infiltration, foam cell formation, oxidative stress, and inflammatory responses, while regulating PLCB2 in chemokine signaling; silencing TMEM106A alleviated these pro-atherosclerotic effects. TMEM106A contributes to AS progression by modulating macrophage-mediated immune responses and chemokine signaling, as validated in experimental models. These findings support its potential as a clinically relevant biomarker and promising therapeutic target for AS intervention. Show less