To investigate the mechanisms underlying sevoflurane-induced POCD, C57BL/6 J mice and SH-SY5Y cells were treated with sevoflurane for model establishment. After the treatment with sevoflurane, CCK-8, Show more
To investigate the mechanisms underlying sevoflurane-induced POCD, C57BL/6 J mice and SH-SY5Y cells were treated with sevoflurane for model establishment. After the treatment with sevoflurane, CCK-8, EdU and flow cytometry were employed to detect cell damage. The levels of N6-methyladenosine (m6A), METTL14 and DUSP6 were determined by qPCR and Western blot. The interaction between METTL14 and DUSP6 was analyzed using RIP-qPCR and Me-RIP methodologies. The cognitive function in mice were assessed by water maze test. After sevoflurane treatment, the cell viability, cell proliferation and METTL14 expression were markedly suppressed, while apoptosis was significantly enhanced. METTL14 overexpression elevated the levels of m6A and DUSP6, increased the binding level of METTL14 to DUSP6 mRNA, reducing damage to cells and cognitive dysfunction of mice. Knockdown of DUSP6 negated the beneficial effects observed with METTL14 overexpression. Sevoflurane induced POCD by regulating METTL14/DUSP6 through m6A methylation. Show less
To investigate the mechanism of liraglutide affecting lipid metabolism by regulating lipolysis and lipogenesis in cells and ob/ob mice. 3 T3-L1 cells were treated with liraglutide in vitro, and differ Show more
To investigate the mechanism of liraglutide affecting lipid metabolism by regulating lipolysis and lipogenesis in cells and ob/ob mice. 3 T3-L1 cells were treated with liraglutide in vitro, and differentially expressed genes were screened by RNA sequencing. Gene Ontology (GO) and KEGG (Kvoto Encyclopedia of Genes and Genomes) enrichment analyses identified target genes for lipid regulation of liraglutide. 3 T3-L1 preadipocytes were induced to differentiate into adipocytes using a "cocktail method". Western blot and immunofluorescence were used to detect the expression of target genes and the lipid regulatory effect of liraglutide. 3 T3-L1 preadipocytes were transfected with lentivirus overexpressing Zbtb20 to study its role in adipogenesis, and gene expression was analyzed by RT-qPCR and Western blot. In vivo, ob/ob mice were subcutaneously injected with liraglutide or saline for 4 weeks. Blood lipids, adipose tissue volume and adipocyte size were detected. Immunohistochemical analysis and RT-qPCR were used to detect the expression of target genes in adipose tissue. Liraglutide reduced lipid droplets and TG levels and altered the expression of genes related to fatty acid metabolism, lipogenesis, fatty acid oxidation, and adipocyte browning. The results of PCR, Western blot and immunofluorescence confirmed that liraglutide could regulate the adipogenesis by downregulating the transcriptional suppressor ZBTB20, and overexpression of Zbtb20 inhibited the expression of LPL, the key enzyme for lipohydrolysis. Liraglutide regulates lipid metabolism through ZBTB20-LPL pathway to reveal its molecular mechanism. 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
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
Yuwen Guo, Huai Bai, Linbo Guan+4 more · 2025 · Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · added 2026-04-24
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 Show more
To assess the association between the single nucleotide polymorphisms (SNP) rs174575 and rs2845574 of the fatty acid desaturase 2 (FADS2) gene and gestational diabetes mellitus (GDM). A total of 1 514 pregnant women who visited West China Second University Hospital of Sichuan University between January 1, 2013 and December 31, 2021 were enrolled in this study. Among them, 583 were diagnosed with gestational diabetes mellitus (GDM group), and 931 had normal pregnancies (control group). The SNPs rs174575 and rs2845574 of the FADS2 gene were analyzed using Sanger DNA sequencing. Plasma levels of insulin (INS), apolipoprotein A1 (apoA1) and apolipoprotein B (apoB) were measured using enzymatic methods, chemiluminescence and immunoturbidimetry. This study was approved by the Medical Ethics Committee of the West China Second University Hospital of Sichuan University (Ethics No.: 2020-036). The main genotype at the rs174575 C/G and rs2845574 C/T loci were CC in both GDM and control groups. No significant difference was found between the GDM and control groups regarding the genotypic or allelic frequencies of rs174575 and rs2845574 sites (P > 0.05). Among the GDM group, individuals with the GG genotype at the rs174575 site had lower plasma HDL-C levels compared to those with the CC genotype (P < 0.05), and had higher atherogenic indices (AI) compared with the CC and CG genotype (P < 0.05; P < 0.05). Individuals with the TT genotype at the rs2845574 site had higher AI compared with the CT genotype (P < 0.05). Among the control group, individuals with the GG genotype had lower diastolic blood pressure (DBP) compared to those with the CC genotype (P < 0.05). Additional subgroup analysis demonstrated that the rs174575 polymorphism was associated with AI levels in obesity subgroup of GDM, TG levels in non-obese subgroup of control and DBP levels in the obese subgroup of control (P < 0.05; P < 0.05; P < 0.05). The FADS2 rs174575 and rs2845574 polymorphisms in GDM patients are associated wit HDL-C and AI levels, and the FADS2 rs174575 polymorphisms was also associated with DBP levels in normal pregnant women. The AI and DBP levels have a BMI-dependent effect. 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
Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection te Show more
Injectable hydrogel implants represent a promising therapeutic approach for ischemic heart failure; but their efficacy is often limited by low bioactivity, poor durability, and inadequate injection techniques. Herein, a unique hydrogel incorporating extracellular matrix from fish swim bladder (FSB-ECM), which has distinct advantages over mammalian derived ECM, such as low antigenicity, bioactivity, and source safety, is developed. It consists of collagen, glycoproteins, and proteoglycans, including 13 proteins common in the myocardial matrix and three specific proteins: HSPG, Col12a1, and vWF. This hydrogel enhances cardiac cell adhesion and stretching while promoting angiogenesis and M2 macrophage polarization. In addition, its storage modulus (G') increases over time, reaching about 1000 Pa after 5 min, which facilitates transcatheter delivery and in situ gelling. Furthermore, this hydrogel provides sustained support for cardiac contractions, exhibiting superior longevity. In a rat model of ischemic heart failure, the ejection fraction significantly improves with FSB-ECM treatment, accompanied by increased angiogenesis, reduced inflammation, and decreased infarct size. Finally, RNA sequencing combined with in vitro assays identifies ANGPTL4 as a key protein involved in mediating the effects of FSB-ECM treatment. Overall, this new injectable hydrogel based on FSB-ECM is suitable for transcatheter delivery and possesses remarkable reparative capabilities for treating heart failure. Show less
Podocyte injury is central to diabetic kidney disease (DKD) pathogenesis, however, the mechanisms underlying podocyte loss remain unclear. Emerging evidence underscores the involvement of fibroblast g Show more
Podocyte injury is central to diabetic kidney disease (DKD) pathogenesis, however, the mechanisms underlying podocyte loss remain unclear. Emerging evidence underscores the involvement of fibroblast growth factors (FGFs) in renal pathophysiology. Here we reveal a previously unappreciated role of podocyte-secreted FGF4 in safeguarding renal function. FGF4 expression is downregulated in renal tissues from DKD patients and animal models, correlating with disease severity. Podocyte-specific deletion of Fgf4 exacerbated podocyte loss and accelerated DKD progression in mice. Conversely, treatment with recombinant FGF4 (rFGF4) improved glomerular filtration and reduced renal injury and fibrosis in diabetic male mice. These effects are primary mediated by activating the FGFR1-AMPK-FOXO1 signaling cascade in podocytes, which mitigates oxidative stress, suppresses apoptosis, and fosters podocyte survival. Notably, rFGF4 also restores the morphology and function of human podocytes exposed to high glucose. Our findings establish FGF4 as a critical regulator of podocyte homeostasis and a potential therapeutic target for DKD. Show less
Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit ant Show more
Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit anti- Mycobacterium tuberculosis (Mtb) properties, have also been demonstrated in macrophages infected with Mtb. However, the exact mechanism remains unclear. This study aimed to clarify the potential molecular mechanisms through which IL-27 enhances macrophage resistance to Mtb infection. Both normal and PTB patients provided bronchoalveolar lavage fluid (BALF). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and stimulated with 50 ng/mL macrophage-colony stimulating factor (M-CSF) to obtain monocyte-derived macrophages (MDMs). Using 100 ng/mL phorbol 12-myristate 13-acetate (PMA), THP-1 cells were induced to differentiate into THP-1-derived macrophage-like cells (TDMs). Both MDMs and TDMs were subsequently infected with the Mtb strain H37Rv and treated with 50 ng/mL IL-27 prior to infection. The damage and inflammation of macrophages were examined using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Patients with PTB had elevated levels of IL-27 in their BALF. Preconditioning with IL-27 was shown to reduce H37Rv-induced MDMs and TDMs apoptosis while also decreasing the levels of Cleaved Caspase-3, Bax and the proinflammatory cytokines TNF-α, IL-1β, and IL-6, promoting the expression of Bcl-2 and the anti-inflammatory factors IL-10 and IL-4. Silencing of the IL-27 receptor IL-27Ra increased macrophage damage and inflammation triggered by H37Rv. Mechanistically, IL-27 activates autophagy by inhibiting TLR4/NF-κB signaling and activating the PI3K/AKT signaling pathway, thereby inhibiting H37Rv-induced macrophage apoptosis and the inflammatory response. Our study suggests that IL-27 alleviates H37Rv-induced macrophage injury and the inflammatory response by activating autophagy and that IL-27 may be a new target for the treatment of PTB. Show less
Familial chylomicronemia syndrome (FCS) is a rare Mendelian autosomal recessive disorder (MIM 238600) characterized by extreme and sustained hypertriglyceridemia due to profound reduction of lipoprote Show more
Familial chylomicronemia syndrome (FCS) is a rare Mendelian autosomal recessive disorder (MIM 238600) characterized by extreme and sustained hypertriglyceridemia due to profound reduction of lipoprotein lipase (LPL) activity. This expert opinion statement synthesizes current knowledge on the definition, pathophysiology, genetics, prevalence, diagnosis, and management of FCS. FCS typically manifests at a young age with persistent severe hypertriglyceridemia-defined as ≥10 mmol/L (≥885 mg/dL), or ≥1000 mg/dL (≥11.2 mmol/L) depending on region and whether Systeme International (SI) units are utilized-in the absence of secondary factors, resistance to conventional lipid-lowering therapies, and a high lifetime risk of acute pancreatitis. It is caused by biallelic pathogenic variants in the LPL gene encoding LPL, or 1 of 4 other related genes that encode proteins that interact with LPL. Affected individuals require a strict, lifelong very low-fat diet with <15% of energy from fat. Emerging therapies inhibiting apolipoprotein C-III show promise in reducing serum triglycerides and pancreatitis risk in patients with FCS. A multidisciplinary approach, encompassing dietary management, pharmacotherapy, and patient education, is pivotal in mitigating the significant morbidity associated with FCS. Show less
R-loop is a common chromatin feature consisting of a displaced single-stranded DNA and an RNA-DNA hybrid, and dysregulation of R-loop surveillance results in genomic and transcriptomic instability. Al Show more
R-loop is a common chromatin feature consisting of a displaced single-stranded DNA and an RNA-DNA hybrid, and dysregulation of R-loop surveillance results in genomic and transcriptomic instability. Although the RNA moiety of most R-loops originates from linear transcripts, circular RNAs (circRNAs), outputs from back-splicing, can also hybridize with the complementary strand of a DNA duplex. However, how circRNA-associated R-loops (ciR-loops) are monitored remains elusive. Here, we identify the DEAD-box RNA helicase Brr2 as an evolutionarily-conserved ciR-loop repressor with dual roles in inhibiting circRNA generation and resolving harmful ciR-loops. Accumulation of ciR-loops caused by loss-of-function of this dual-action factor induces antisense transcription and premature transcription termination for many genes and generates significant DNA damage, which further leads to a series of defects in DNA replication, cell division and cell proliferation. We propose that functional integration of multilayered regulation by a single protein can be an efficient double protection against genome instability. Show less
Spontaneous Achilles tendon rupture (SATR) predominantly affects middle-aged and elderly individuals with chronic injuries. However, the exact cause and mechanism of SATR remain elusive, and potential Show more
Spontaneous Achilles tendon rupture (SATR) predominantly affects middle-aged and elderly individuals with chronic injuries. However, the exact cause and mechanism of SATR remain elusive, and potential therapeutic intervention or prevention is still insufficient. The present study aimed to uncover the key pathological molecules by using iTRAQ proteomics. The results identified 2432 candidate proteins in SATR patients using iTRAQ proteomic analysis. A total of 307 differentially expressed proteins (DEPs) were identified and linked to 211 KEGG signaling pathways including Coronavirus disease (COVID-19), focal adhesion, and ribosomes. GO enrichment analysis highlighted significant enrichment in processes such as biological adhesion, ossification, lipid (APOA4) processes, and extracellular matrix (ECM) organization (collagen). PPI network analysis identified hub genes such as serum albumin (ALB), fibronectin (FN1), and actin cytoplasmic 1. The WB analysis confirmed that FN1 and the receptor for activated C kinase (RACK1) were downregulated in the SATR tendon. Immunohistochemical staining revealed that collagen I and III were suppressed, while collagen II and APOA4 expression were higher in the SATR pathological tissue ( Show less
Angiopoietin-like protein 4 (ANGPTL4) is a hepatokine implicated in fat metabolism regulation. Its genetic inactivation has been associated with improved glucose homeostasis, while elevated plasma ANG Show more
Angiopoietin-like protein 4 (ANGPTL4) is a hepatokine implicated in fat metabolism regulation. Its genetic inactivation has been associated with improved glucose homeostasis, while elevated plasma ANGPTL4 levels are observed in diabetic and obese individuals. However, the potential link between ANGPTL4 and diabetes- or obesity-related complications remains uncertain. This study aimed to explore whether plasma ANGPTL4 level could serve as a predictor of cancer mortality, cardiovascular mortality, and all-cause mortality in a community-based cohort. A community-based cohort study was conducted, where fasting plasma ANGPTL4 concentrations were measured at baseline, and vital status was ascertained through linkage with the National Health Insurance Research Database in Taiwan. During a 10.46-year follow-up period, 29 (2.49%) of the 1163 participants died. Subjects within the highest tertile of plasma ANGPTL4 levels exhibited the lowest survival rate. In unadjusted models, plasma ANGPTL4 significantly predicted all-cause mortality, cancer mortality, and cardiovascular or cancer-related mortality. Upon adjustment for confounders including age, sex, smoking, body mass index (BMI), hypertension, diabetes mellitus (DM), and renal function, each standard deviation increase in plasma ANGPTL4 was associated with HRs of 1.35 (95% CI: 1.01-1.80, Plasma ANGPTL4 emerges as a promising biomarker capable of predicting 10-year mortality and enhancing risk prediction beyond established risk factors. Show less
This study evaluated the protective effects of naringin (NG) against intestinal injury in 7-day-old piglets infected with porcine epidemic diarrhea virus (PEDV). Eighteen piglets (Duroc × Landrace × L Show more
This study evaluated the protective effects of naringin (NG) against intestinal injury in 7-day-old piglets infected with porcine epidemic diarrhea virus (PEDV). Eighteen piglets (Duroc × Landrace × Large, body weight = 2.58 ± 0.05 kg) were divided into three treatment groups based on similar body weights and equal numbers of males and females: the blank control group (CON group), the PEDV infection group (PEDV group), and the NG intervention + PEDV infection group (NG + PEDV group) ( Show less
Parkinson's disease (PD) is a neurodegenerative disorder caused by complex genetic and environmental factors. Genome-edited human pluripotent stem cells (hPSCs) offer a unique experimental platform to Show more
Parkinson's disease (PD) is a neurodegenerative disorder caused by complex genetic and environmental factors. Genome-edited human pluripotent stem cells (hPSCs) offer a unique experimental platform to advance our understanding of PD etiology by enabling the generation of disease-relevant cell types carrying patient mutations along with isogenic control cells. To facilitate this approach, we generated a collection of 65 human stem cell lines genetically engineered to harbor high risk or causal variants in genes associated with PD ( Show less
Sepsis-associated acute lung injury (SA-ALI), a critical complication of sepsis, is characterized by immune dysregulation-induced pulmonary dysfunction. Shenmai Injection (SMI) is a standardized herba Show more
Sepsis-associated acute lung injury (SA-ALI), a critical complication of sepsis, is characterized by immune dysregulation-induced pulmonary dysfunction. Shenmai Injection (SMI) is a standardized herbal preparation consisting of Panax ginseng C.A.Mey (Hongshen) and Ophiopogon japonicus (Thunb.) Ker Gawl (Maidong), traditionally used for qi-replenishing, collapse-stabilizing, and lung-moistening therapy. Although clinically utilized in the management of SA-ALI, the specific mechanisms by which it acts against SA-ALI necessitate further investigation. The present study endeavors to comprehensively determine the therapeutic efficacy of SMI against SA-ALI through an integrated approach combining network pharmacology, metabolomics, metagenomic sequencing, and experimental validation. In this study, murine SA-ALI was established using lipopolysaccharide (LPS) and Poly(I:C). Results indicated that SMI administration significantly attenuated pulmonary inflammation, restored blood-gas barrier integrity, reduced serum pro-inflammatory cytokines and suppressed NF-κB pathway activation in SA-ALI mice. Network pharmacology elucidated the multi-targeted mechanism of SMI in modulating steroid hormone biosynthesis. Integrated metabolomics and target analysis revealed that ophiopogonin A/B and luteolin in SMI alleviates metabolic dysregulation by targeting key enzymes, including AKR1C3, HSD17B1/2, and SULT1E1. Metagenomic profiling demonstrated SMI-mediated gut microbiota remodeling, marked by suppression of pathogenic Chlamydiaceae (particularly Chlamydia abortus) and enrichment of commensal Lactobacillaceae. Correlation analysis showed that intestinal androstenedione and androsterone levels during SMI treatment recovery were negatively correlated with Chlamydia abortus abundance. In conclusion, SMI enhances the recovery from sepsis-associated SA-ALI by dual modulation of gut microbial ecology and host metabolic homeostasis, thereby establishing its potential as a multi-mechanistic therapeutic candidate for sepsis-related organ injury. 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 (P Show more
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
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined r Show more
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities through in silico analysis of ligand-receptor interactions. Consequently, we identified a B cell subset that expressed cytokine interleukin-27 (IL-27) and chemokine CXCL10. Through the IL-27-IL-27 receptor interaction, these IL-27/CXCL10-producing B cells targeted CD40-activated B cells in vitro and, upon induction by immunization and viral infection, optimized antibody responses and antiviral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 interaction-mediated self-targeting, these cells promoted B cell PD-L1 expression and immune evasion. Mechanistically, Show less
This study aimed to develop and apply a novel computational pipeline combining SELFormer, a transformer architecture-based chemical language model, with advanced deep learning techniques to predict na Show more
This study aimed to develop and apply a novel computational pipeline combining SELFormer, a transformer architecture-based chemical language model, with advanced deep learning techniques to predict natural compounds (NCs) with potential in Alzheimer's disease (AD) treatment. The NCs were identified based on activity related to seven AD-specific genes, including acetylcholinesterase (AChE), amyloid precursor protein (APP), beta-secretase 1 (BACE1), and presenilin-1 (PSEN1). We implemented a computational pipeline using SELFormer and deep learning techniques, conducted optimal clustering and quantitative structure-activity relationship (QSAR) analyses, and performed a uniform manifold approximation and projection (UMAP) to categorize compounds based on bioactivity levels. Molecular docking analysis was carried out on selected compounds. To validate the computational predictions, we conducted in vitro studies using nerve growth factor (NGF)-differentiated PC12 cells. Finally, we mapped the relationships between food sources containing the identified compounds and their target proteins. Optimal clustering analysis revealed five distinct groups of NCs, while QSAR analysis highlighted variations in molecular properties across clusters. The UMAP projection identified 17 highly active NCs (pIC This integrated computational and experimental approach offers a promising framework for identifying potential NCs for AD treatment. The results contribute to exploring effective therapeutic strategies against AD. Show less
The objective of this study was to assess the correlation between the ApoB/ApoA ratio and the recurrence of kidney stones in a Chinese adult population. We collected electronic records of patients wit Show more
The objective of this study was to assess the correlation between the ApoB/ApoA ratio and the recurrence of kidney stones in a Chinese adult population. We collected electronic records of patients with kidney stones who underwent surgical treatment at our hospital from March 2016 to March 2022. These patients were followed up and categorized into groups based on the recurrence of kidney stones. Parameters related to routine blood and biochemical tests, as well as the history of hypertension and diabetes mellitus, were gathered. Multiple imputation was applied for missing data. Subsequently, differences between the recurrence and non-recurrence groups were assessed using the chi-square test, independent samples t test, or Wilcoxon rank sum test. Logistic regression analysis, subgroup analysis, and propensity-matched analysis were conducted to evaluate the relationship between the ApoB/ApoA ratio and kidney stone recurrence. The study included a total of 923 participants aged > 18 years, among whom 296 experienced kidney stone recurrence during the follow-up period. An elevated ApoB/ApoA ratio was identified as a risk factor for kidney stone recurrence (adjusted OR = 2.48, 95% CI 1.04, 5.92). Propensity-matched analyses further supported the association, showing that elevated ApoB/ApoA ratios were linked to a higher risk of renal stone recurrence (OR = 3.37, 95% CI 1.24-9.17). The dose-response curve illustrated a positive linear correlation between the ApoB/ApoA ratio and the risk of kidney stone recurrence. Increased ApoB/ApoA ratios are positively correlated with the risk of kidney stone recurrence. This association remains significant, although a causal relationship cannot be definitively established. Show less
To investigate the risk factors associated with coronary heart disease (CHD) in patients with metabolic-associated fatty liver disease (MAFLD) and develop a nomogram prediction model. This study inclu Show more
To investigate the risk factors associated with coronary heart disease (CHD) in patients with metabolic-associated fatty liver disease (MAFLD) and develop a nomogram prediction model. This study included 394 patients with MAFLD who underwent coronary angiography at The Affiliated Hospital of Qingdao University between December 2019 and December 2024. The study cohort was divided in a 7:3 ratio into training and validation sets comprising 277 and 117 cases, respectively. The training group was further divided into the MAFLD-only ( Of the 394 MAFLD cases, 313 had CHD-related complications. Of the 277 patients in the training set, 220 had CHD, and of the 117 patients in the validation set, 93 had CHD. LASSO regression analysis revealed that the following variables were associated with the risk of CHD: sex, lipoprotein(a) (Lp[a]), low-density lipoprotein cholesterol, white blood cell count (WBC), glycated triglyceride-glucose index (TyG), and atherosclerosis index (AIP). Multivariate logistic regression analysis revealed that sex, Lp(a), WBC, TyG, and AIP were independent risk factors for CHD in MAFLD cases. A nomogram was constructed and an ROC curve was plotted, based on which the optimal cutoff value was determined as 0.698. The area under the curve of the nomogram in the training and validation cohorts was 0.860 (95% CI = 0.807-0.913) and 0.843 (95% CI = 0.757-0.929), respectively. Calibration curves for CHD risk probability showed good agreement between the nomogram's predicted probabilities and the observed event rates. DCA demonstrated the net clinical benefit of the constructed nomogram. Sex, Lp(a), WBC, TyG, and AIP emerged as independent risk factors for CHD in patients with MAFLD and the nomogram prediction model constructed using these factors could effectively predict CHD occurrence. Show less
Cognitive decline is prevalent among older adults and may be associated with their daily activity behaviours. However, no studies have examined how cognitive decline affects older adults' activity beh Show more
Cognitive decline is prevalent among older adults and may be associated with their daily activity behaviours. However, no studies have examined how cognitive decline affects older adults' activity behaviours within a 24-h framework. This study investigates the relationship between cognitive function and 24-h activity behaviours in older adults, further exploring whether these associations differ by sex. This study analyses data from the eighth wave of the Survey of Health, Ageing and Retirement in Europe, conducting a cross-sectional analysis of 814 older adults. Cognitive function was assessed using the SHARE-Cog tool, encompassing 10-word immediate recall, 10-word delayed recall, verbal fluency, and self-reported memory. 24-h activity behaviours (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA], sedentary behaviour [SB], and sleep) were objectively measured with thigh-worn accelerometers. Compositional multivariate linear regression models were constructed using compositional data as the response variable, with cognitive function measures as predictors. Higher MVPA was linked to better cognitive outcomes (verbal fluency, 10-word immediate recall, and 10-word delayed recall) while SB and longer sleep related to poorer performance, with these associations being stronger in women (model p ≤ 0.001). Among women, cognitive outcomes were significantly associated with all activity behaviours (p range = 0.010-0.045). Women who self-reported poor memory and scored 0 on the verbal fluency spent approximately 45% of their day in SB, whereas those reporting excellent memory and scoring 60 spent 40.06% (37.18%, 42.86%) and 36.41% (31.53%, 41.10%) of their day sedentary, respectively. In contrast, men's 24-h activity composition did not vary significantly with cognitive function (p range = 0.051-0.845). Older adults with better cognitive function tend to engage in more PA and reduce sedentary and sleep time. This relationship differed by sex, with females' activity behaviours being more sensitive to cognitive function changes. These findings suggest that interventions promoting healthy lifestyles in older adults should account for cognitive function, particularly in females. Show less
Xiaolei Song, Chenchen Wang, Qin Ding+8 more · 2025 · Journal of controlled release : official journal of the Controlled Release Society · Elsevier · added 2026-04-24
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. The vicious circle between amyloid-β peptide (Aβ) overgeneration and microglial dysfunction is an important path Show more
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. The vicious circle between amyloid-β peptide (Aβ) overgeneration and microglial dysfunction is an important pathological event that promotes AD progression. However, therapeutic strategies toward only Aβ or microglial modulation still have many problems. Herein, inspired by the Aβ transportation, an Aβ-derived peptide (CKLVFFAED) engineered biomimetic nanodelivery system (MK@PC-R NPs) is reported for realizing BBB penetration and reprogram neuron and microglia in AD lesion sites. This hollow mesoporous Prussian blue-based MK@PC-R NPs carrying curcumin and miRNA-124 can down-regulate β secretase expression, thereby inhibiting Aβ production and reducing Aβ-induced neurotoxicity. Meanwhile, MK@PC-R NPs with excellent antioxidant and anti-inflammatory properties could normalize the microglial phenotype and promote Aβ degradation, providing neuroprotection. As expected, after treatment with MK@PC-R NPs, the Aβ burdens, neuron damages, neuroinflammation, and memory deficits of transgenic AD mice (APP/PS1 mice) are significantly attenuated. Overall, this biomimetic nanodelivery system with anti-Aβ and anti-inflammatory properties provides a promising strategy for the multi-target therapy of early AD. 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
The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the m Show more
The genetic foundations underlying the observed disease resistance in certain indigenous pig breeds, notably the Min pigs of China, present a compelling underexplored subject of study. Exploring the mechanisms of disease resistance in these breeds could lay the groundwork for genetic improvements in pig immunity, potentially augmenting overall pig productivity. In this study, whole blood samples were collected from pre- and post- swine fever vaccinated Min and Large White pigs for transcriptome sequencing. The mRNA and lncRNA in both pig breeds were analyzed, and intra-group and inter-group comparisons were also conducted. The results indicated that a greater number of immune-related pathways such as the JAK-STAT and PI3K-AKT signaling were enriched in Min pigs. Furthermore, genes involved in inflammation and antiviral responses, including IL16, IL27, USP18, and DHX58, were upregulated in post-vaccination Min pigs compared to post-vaccination Large White pigs. This heightened immune responsiveness could contribute to the observed differences in disease resistance between Min pigs and Large White pigs. Show less
Although light-intensity physical activity (LPA) has been suggested to be associated with a lower risk of mortality, the minimal and optimal volumes of LPA remain unclear. We aimed to examine the mini Show more
Although light-intensity physical activity (LPA) has been suggested to be associated with a lower risk of mortality, the minimal and optimal volumes of LPA remain unclear. We aimed to examine the minimal and optimal volumes of LPA associated with the risks of mortality and disease incidence (i.e., cardiovascular diseases and cancer). Data were derived from the population-based UK Biobank cohort study, including 69,492 adults aged 43-78 years. Accelerometer-measured LPA was defined using a validated, published machine learning-based Random Forest activity method, which was categorized into 4 quartile groups. All-cause and cause-specific mortality (cardiovascular disease- and cancer-specific) were determined according to the International Classification of Diseases, 10th version codes. Disease incidence was defined based on primary care, hospitalization, or death records. During a median follow-up period of 8.04 years, 2024 adults died from all causes, 539 from cardiovascular disease, and 1175 from cancer. For all-cause mortality, compared with participants in the lowest quartile of LPA (<3.9 h/day), the hazard ratios (HRs) and 95% confidence intervals (95%CIs) were 0.82 (95%CI: 0.73‒0.93) for those with 3.9 to <5.0 h/day, 0.75 (95%CI: 0.66‒0.85) for those with 5.0 to <6.1 h/day, and 0.77 (95%CI: 0.68‒0.88) for those with ≥6.1 h/day, respectively. There was an inverse non-linear dose-response association between LPA and all-cause mortality, with an optimal dose of 5.72 h/day (95%CI: 5.45‒6.41; HR = 0.63, 95%CI: 0.56‒0.71) and a minimal dose of 3.59 h/day (95%CI: 3.53-8.56; HR = 0.81, 95%CI: 0.78‒0.86), with the 5th percentile as the reference. Similar patterns were observed for cause-specific mortality and disease incidence (cardiovascular disease and cancer). Engaging in LPA for ∼3.5 h/day was conservatively associated with lower risk of mortality and disease incidence, with further risk reductions observed up to an optimal dose of ∼6.0 h/day. These findings suggest that sufficient LPA offers important health benefits, which can inform the development of future PA guidelines. Show less
Pork serves as a significant meat commodity, with intramuscular fat (IMF) content being a critical determinant of its quality. However, the epigenetic mechanism of porcine IMF deposition is still uncl Show more
Pork serves as a significant meat commodity, with intramuscular fat (IMF) content being a critical determinant of its quality. However, the epigenetic mechanism of porcine IMF deposition is still unclear. This study integrated proteomics and lactylation profiles from the longissimus thoracis (LT) muscles of pigs with extremely high (IMF_H) and extremely low (IMF_L) IMF content to clarify the association between lactylation and porcine fat deposition. Furthermore, an intramuscular preadipocyte induction and differentiation model was conducted to elucidate the changes in lactylation during adipocyte differentiation. Finally, the regulatory role of lactylation in adipocyte differentiation was explored by modulating lactate production during the induction and differentiation of preadipocytes. Proteomic analysis revealed significantly increased expression of key lipid metabolism related proteins (FASN, APOA4, FABP4, ACLY, PLIN1) in IMF_H pig muscle tissues compared with IMF_L tissues, along with substantial activation of lipid metabolism pathways. Lactylation profiling identified 95 differential lysine sites across 56 proteins, with most showing lower lactylation levels in the IMF_H group. The integrative omics analysis revealed differences in lactylation profiles in porcine LT tissues with varying efficiencies of IMF deposition, highlighted PGK1, PKM, and PYGM as central lactylation-modified proteins in porcine fat deposition regulation. Further in vitro study proved that lactate-mediated lactylation inhibited adipogenic differentiation of porcine intramuscular preadipocytes through PPARγ signaling pathway. This study clarified the changes in the lactylation profile in porcine LT tissues with varying efficiencies of IMF deposition, and demonstrated that lactate-mediated lactylation inhibits the PPARγ signaling pathway and the adipogenic differentiation of porcine intramuscular preadipocyte. This study provided a new insight to understanding the epigenetic regulation mechanisms of lipid deposition in pigs. Show less