👤 Quotao Lu

Pathological retinal angiogenesis drives vision loss in diseases like proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO). Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has shown therapeutic potential in FGFR-mutated urothelial carcinoma. This study aimed to determine whether erdafitinib suppresses pathological retinal angiogenesis beyond its canonical FGFR inhibition, and to dissect its potential mechanisms through multi-model validation. We employed zebrafish developmental angiogenesis and oxygen-induced retinopathy (OIR) mouse models, combined with in vitro endothelial cell assays. In zebrafish, erdafitinib dose-dependently inhibited intersegmental vessel (ISV) formation and disrupted retinal angiogenesis, with confocal microscopy revealing truncated vascular length (by 62% at 4 µM vs. controls). The OIR model demonstrated erdafitinib's efficacy in reducing neovascular density (35% decrease) and pathological tuft formation. Mechanistically, erdafitinib impaired human umbilical vein endothelial cell (HUVEC) tube formation and migration, accompanied by downregulation of VEGFR2 expression (2.1-fold reduction) and inhibition of AKT/ERK phosphorylation. Molecular docking confirmed erdafitinib's binding to VEGFR2 kinase domain (binding energy: -7.8 kcal/mol), albeit with lower affinity than FGFR1 (-10.2 kcal/mol). These findings establish that erdafitinib exerts off-target anti-angiogenic effects by blocking VEGFR2 phosphorylation and downstream signaling, supporting its repurposing potential for anti-VEGF-resistant retinal vascular diseases. Further studies should address its intraocular pharmacokinetics and long-term safety. Show less

The development of FGFR1-driven stem cell leukemia and lymphoma syndrome (SCLL) in mouse models is accompanied by an increase in highly heterogenous myeloid derived suppressor cells (MDSCs), which promote immune evasion. To dissect this heterogeneity, we used a combination of CyTOF and scRNA-Seq to define the phenotypes and genotypes of these MDSCs. CyTOF demonstrated increased levels of circulating macrophages in the peripheral blood of leukemic mice, and flow cytometry demonstrated that these macrophages were derived from Ly6C Show less

Aberrant activation of fibroblast growth factor receptors (FGFRs) plays a critical role in tumorigenesis across multiple cancer types, driving the development of various FGFR inhibitors. Despite clinical advances, therapeutic efficacy remains limited by the emergence of drug resistance, primarily mediated by gatekeeper mutations in FGFRs. To overcome this challenge, we designed and synthesized a novel series of 7-(1-methyl-1 Show less

The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive virtual screening protocol that combines energy-based screening and machine learning techniques, leading to the identification of a novel compound, Show less

The high mortality rate of severe heat stroke is mainly related to multiple organ dysfunction syndrome (MODS), and respiratory failure caused by acute lung injury (ALI) is a significant factor in the development of MODS during the course of severe heat stroke. Previous research has demonstrated that severe heat stroke-induced acute lung injury (sHS-ALI) is associated with an increase in reactive oxygen species (ROS) in vascular endothelial cells (VECs), but the specific initiating factors and intermediate mechanisms involved are unclear. In this study, the mRNA profiles of mouse lung tissues were analysed using high-throughput sequencing. Genome-wide knockout was performed using CRISPR-Cas9 technology to identify a cohort of differentially expressed genes that promote human umbilical vein endothelial cells survival after heat stress. The expression of key proteins [fibroblast growth factor 23 (FGF23), phosphorylated fibroblast growth factor receptor-1 (p-FGFR-1), FGFR-1, phosphorylated phospholipase C-γ2 (p-PLC-γ2), PLC-γ2, p-p47 In this study, we first screened sHS-ALI target genes by cross-comparison This study confirmed that FGF23/FGFR1 signalling, as an upstream priming factor, mediated NOX2-ROS activation in VECs after heat stress, thus participating in the sHS-ALI process. FGFR-1 Y766 phosphorylation is essential for FGF23/FGFR-1 signalling activation in VECs, which is involved in sHS-ALI. These findings further clarify the mechanism underlying sHS-ALI and contribute to reducing the mortality and morbidity of severe heat stroke. Show less

A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Show less

The selective inhibition of fibroblast growth factor receptors (FGFR) presents a significant challenge due to the high degree of sequence and the close structural similarity of the subtypes. Herein, we designed selective dual FGFR2/3 inhibitors based on the in-depth understanding of protein-ligand interaction contributions. We efficiently identified ISM7594 ( Show less

Parkinson's disease (PD), as a neurodegenerative disorder, is characterized primarily by damage to the central nervous system, accompanied by astrocyte dysfunction and the activation of ferroptosis. Recent studies have shown that oligodendrocytes also exhibit functional abnormalities in the brains of PD patients and are involved in the ferroptotic process. However, it remains unclear whether there is an interaction between oligodendrocytes and astrocytes and how they induce neuronal ferroptosis. Here, we employed single-nucleus sequencing and spatial transcriptomics to characterize the intercellular communication network between oligodendrocytes and astrocytes in the PD environment. Among these, astrocytes are the primary recipients of signals sent by oligodendrocytes in the FGF (Fibroblast growth factors) signaling pathway. In PD, the communication intensity is weakened, involving FGF1 and FGF9 and their receptors FGFR1, FGFR2, and FGFR3. Subsequently, we further validated the significant activation of mitochondrial oxidative phosphorylation processes within oligodendrocytes and astrocytes in PD mice, and that astrocytes might also involve the interaction of Mt1 and Ca Show less

This study investigated the impact of alterations in six key genes ( Genomic data from five datasets were merged to identify 437 ESCC patients, categorized into altered ( The altered group exhibited a significantly higher tumor mutational burden (TMB) and mutation count than the unaltered group ( This study highlights that genomic alterations in these six genes are associated with poorer OS in ESCC, despite higher TMB potentially increasing tumor neo-antigens. These findings underscore the need for further research to explore their prognostic and therapeutic potential. Show less

Diabetic retinopathy (DR) is the leading manifestation of diabetic microangiopathy. However, effective biomarkers and therapies are lacking. Circular RNAs (circRNAs) have been implicated in various diseases including DR. However, the role of circRNAs in DR remains elusive. In the present study, circNXN was upregulated in high glucose (HG)-treated human retinal microvascular endothelial cells (hRMECs). circNXN knockdown inhibited the proliferation, migration, and angiogenesis of hRMECs and promoted apoptosis. In addition, circNXN acted as a sponge for miR-338-3p to facilitate the FGFR1 (fibroblast growth factor receptor 1) expression. Furthermore, rescue assays revealed that the reduced promoting effect on hRMECs induced by the knockdown of circNXN could be reversed by a miR-338-3p inhibitor in HG-treated hRMECs. Additionally, in a DR rat model, circNXN downregulation ameliorated retinal vasculature changes. Our findings reveal a new therapeutic strategy for DR that may provide a new approach to clinical DR therapy. Show less

Fibroblast growth factor receptors (FGFRs) are established oncogenic drivers in various solid tumors. However, the approved FGFR inhibitors face challenges with acquired resistance and dose-limiting adverse effects associated with FGFR1/4 inhibition, limiting therapeutic efficacy. Herein, we systematically explored linker and electrophile moieties based on the pyrrolopyrazine carboxamide core and identified aniline α-fluoroacrylamide as an effective covalent warhead. Compound Show less

Epithelial-mesenchymal transition (EMT) of alveolar epithelial cells is an important mechanism for the onset and development of broncho-pulmonary dysplasia (BPD). Fibroblast growth factor 2 (FGF2) is involved in the development and repair of injury in many organs, particularly the lung. The role of FGF2 in BPD is currently unclear. The aim of our study was to investigate the expression of FGF2 in lung tissue of BPD mice, to further clarify the effect of FGF2 on EMT in alveolar epithelial cells and to actively search for possible signaling pathways. The BPD model was induced by exposure to hyperoxia. Lung tissue samples were collected and hematoxylin and eosin staining was used to determine the modeling effect. Quantitative real-time polymerase chain reaction (QRT-PCR), immunohistochemistry was used to detect FGF2 expression in BPD mice. To further investigate the effect of FGF2 supplementation and deficiency on EMT in alveolar epithelial cells, A549 cells were cryopreserved, resuspended, cultured, and passaged. Transforming growth factor-β1 (TGF-β1) was used to induce EMT. FGF2 small interfering RNA fragments were synthesized and screened. Fibroblast growth factor receptor 1 (FGFR1) expression was inhibited by BGJ398. (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium) (MTS) assay was used to detect the effect of FGF2 and infigratinib (BGJ398) on cell proliferation. We used qRT-PCR and Western blot to detect the expression of epithelial cell markers, mesenchymal cell markers and EMT-related signaling pathway proteins. Our results showed that the successful established hyperoxia mice model were characteristic by BPD. Hyperoxia decreased FGF2 on day 4, upregulated FGF2 on day 21, which resulted in EMT. In vitro, we found that FGF2 alone increased the expression of mesenchymal markers, decreased the expression of epithelial markers and activated phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), small mother against decapentaplegic (Smad), mitogen-activated protein kinase (P38), and extracellular signal-regulated kinase (ERK) signaling pathways. FGF2 could not reverse but synergistically promote Transforming growth factor-β1 (TGF-β1)-induced EMT of alveolar epithelial cells. Silencing FGF2 increased the expression of epithelial marker E-cadherin, inhibited the PI3K/AKT, Smad, and P38 signaling pathways activated by TGF-β1, but activated ERK signaling. FGF2 receptor inhibitor BGJ398 reversed TGF-β1-induced EMT, decreased the expression of FGFR1, and inhibited ERK signaling pathway activation. FGF2 was closely associated with EMT in BPD mice. Both high and low levels of FGF2 promoted EMT in A549. The FGF2 receptor inhibitor BGJ398 reversed TGF-β1-induced EMT in A549 by inhibiting the FGFR1/P-ERK signaling pathway. Show less

Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, excess deposition of lipids in hepatic lipid droplets. Despite the growing prevalence and serious risks it poses, including liver decompensation, the need for transplantation, and increased patient mortality, MASH currently faces no approved pharmacotherapy. Several promising treatment candidates have emerged from recent clinical trials, including analogs of FGF21 and agonists of the associated FGFR1-KLB complex. These agents were well-tolerated in trials and have demonstrated significant improvements in both histological and biochemical markers of liver fat content, inflammation, injury, and fibrosis in patients with MASH. Endocrine FGF21 plays a vital role in maintaining homeostasis of lipid, glucose, and energy metabolism. It achieves this through pathways that target lipids or lipid droplets in adipocytes and hepatocytes. Mechanistically, pharmacological FGF21 acts as a potent catabolic factor to promote lipid or lipid droplet lipolysis, fatty acid oxidation, mitochondrial catabolic flux, and heat-dissipating energy expenditure, leading to effective clearance of hepatic and systemic gluco-lipotoxicity and inflammatory stress, thereby preventing obesity, diabetes, and MASH pathologies. In this review, we aim to provide an update on the outcomes of clinical trials for several FGF21 mimetics. We compare these outcomes with preclinical studies and offer a lipid-centric perspective on the mechanisms underlying the clinical benefits of these agents for MASH. Show less

Lipid metabolism disorders have been confirmed to be closely related to kidney injury caused by adriamycin (ADR) and obesity, respectively. However, it has not been explored whether lipid metabolism disorders appear progressively more severe after ADR-based chemotherapy in the obese state, and the specific molecular mechanism needs to be further clarified. This study was designed to examine the role of p53-fibroblast growth factor 21 (FGF21) axis in ADR-induced renal injury aggravated by high-fat diet (HFD). We engineered Fgf21 KO mice and used long-term (4 months) and short-term (0.5 months) HFD feeding, and ADR-injected mice, as well as STZ-induced type 1 diabetic mice and type 2 (db/db) diabetic mice to produce an in vivo model of nephrotoxicity. The specific effects of p53/FGF21 on the regulation of lipid metabolism disorders and its downstream mediators in kidney were subsequently elucidated using a combination of functional and pathological analysis, RNA-sequencing, molecular biology, and in vitro approaches. Long-term HFD feeding mice exhibited compromised effects of FGF21 on alleviation of renal dysfunction and lipid accumulation following ADR administration. However, these impairments were reversed by p53 inhibitor (pifithrin-α, PFT-α). PFT-α sensitized FGF21 actions in kidney tissues, while knockout of Fgf21 impaired the protective effects of PFT-α on lipid metabolism. Mechanistically, p53 impaired the renal expression of FGF receptor-1 (FGFR1) and thereby developed gradually into FGF21 resistance via inhibiting hepatocyte nuclear factor 4 alpha (HNF4α)-mediated transcriptional activation of Fgfr1. More importantly, exogenous supplementation of FGF21 or PFT-α could not only alleviate ADR-induced lipid metabolism disorder aggravated by HFD, but also reduce lipid accumulation caused by diabetic nephropathy. Given the difficulties in developing the long-acting recombinant FGF21 analogs for therapeutic applications, sensitizing obesity-impaired FGF21 actions by suppression of p53 might be a therapeutic strategy for maintaining renal metabolic homeostasis during chemotherapy. 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 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

Suicide is a leading global cause of mortality, with major depressive disorder (MDD) contributing significantly. Neuroimmune mechanisms, particularly inflammation, are increasingly recognized in the pathophysiology of depression and suicidal ideation. This study investigated the relationship between inflammatory cytokines and suicidal ideation in patients with MDD. A two sample Mendelian randomization analysis using Genome-Wide Association Study data was performed to evaluate the associations between 16 inflammatory cytokines and suicidal ideation. Then the patients with MDD, stratified by suicidal ideation severity were assessed for peripheral cytokine levels (interleukin [IL])-2, IL-4, IL-6, IL-10, interferon-gamma [IFN-γ], IL-17, IL-12, IL-27, and tumor necrosis factor-α) using flow cytometry and enzyme-linked immunosorbent assay. MR analysis revealed significant associations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and IL-27 with negative and positive effects, respectively. Individuals with high suicide risk exhibited elevated IL-27, IL-12, IFN-γ and IL-4 compared with low suicide risk. There are genetic associations between IL-27 and suicidal ideation, which is biologically corroborated by elevated peripheral IL-27 levels in high-risk suicidal individuals, highlighting its potential as a clinically viable biomarker for assessing suicidal risk in depressive patients. Show less

Thyroid-associated ophthalmopathy (TAO) is characterized by inflammation and tissue remodeling, including fibrosis and adipogenesis. Here, we identify interleukin-27 (IL-27) as a negative feedback immunomodulator in TAO. Serum IL-27α levels were significantly elevated in patients with TAO compared with healthy and inflammatory disease controls. In orbital fibroblasts (OFs), exogenous IL-27 suppressed IL-1β-induced proinflammatory cytokines and reduced hypoxia-induced NLRP3 inflammasome activation. IL-27 also attenuated TGF-β-driven fibrosis via p38 MAPK signaling in CD90 Show less

Sow colostrum is rich in lactoferrin (LF), which can be orally administered to protect piglets from porcine epidemic diarrhea virus (PEDV) infection, thereby reducing piglet mortality. Previous study has shown that sows fed with recombinant B. subtilis expressing 4,4-diaponeurosporene (B.S-Dia) have significantly higher LF levels in their colostrum compared to sows fed with B. subtilis. This suggests that 4,4-diaponeurosporene (DNP) produced by B.S-Dia may influence LF content in sow colostrum. In this study, we first extracted DNP expressed by the recombinant probiotic using acetone-hexane extraction. Flow cytometry, RT-qPCR, and ELISA analyses demonstrated that DNP promoted dendritic cell (DCs) maturation and increased the expression of IL-1β and IL-27. We then established a method for isolating neutrophils from sow colostrum and set up a co-culture system of neutrophils and DCs to investigate factors regulating LF secretion. The results indicated that DCs secretions enhanced LF expression in neutrophils. Finally, the application of IL-27 inhibitors confirmed that IL-27 produced by DCs upregulates LF secretion in neutrophils. These findings elucidate the mechanism by which DNP promotes LF production in colostrum and provide a theoretical foundation for using B.S-Dia to prevent and control PEDV infection in piglets. Show less

Cognitive impairments in major depressive disorder (MDD) affect patients' social functioning, with underlying mechanisms involving gut microbiota and inflammatory factors remaining unclear. The study analyzed cognitive function, gut microbiota changes, and inflammatory factor levels in 39 unmedicated MDD patients and 41 healthy controls, employing correlation and moderation effect analysis. MDD patients scored lower than controls in cognitive functions like information processing speed, attention/vigilance, verbal learning, visual learning and social cognition. They showed reduced gut microbiota diversity and increased levels of inflammatory markers (TNF-α, IL-1, IL-6, IL-17, IL-27, IL-33). Sellimonas abundance correlated negatively with attention/vigilance, moderated by TNF-α, IL-27, and IL-33. This relationship was stronger at lower inflammation levels. MDD patients exhibit multi-domain cognitive dysfunction alongside pro-inflammatory states and disrupted gut microbiota. The abundance of Sellimonas significantly predicts attention/vigilance deficits. Inflammatory factors modulate the impact of gut microbiota on cognitive function, suggesting chronic low-grade inflammation as a key risk factor for cognitive impairment in MDD. Show less

JMJD1C (Jumonji Domain Containing 1C), a member of the lysine demethylase 3 (KDM3) family, is universally required for the survival of several types of acute myeloid leukemia (AML) cells with different genetic mutations, representing a therapeutic opportunity with broad application. Yet how JMJD1C regulates the leukemic programs of various AML cells is largely unexplored. Here we show that JMJD1C interacts with the master hematopoietic transcription factor RUNX1, which thereby recruits JMJD1C to the genome to facilitate a RUNX1-driven transcriptional program that supports leukemic cell survival. The underlying mechanism hinges on the long N-terminal disordered region of JMJD1C, which harbors two inseparable abilities: condensate formation and direct interaction with RUNX1. This dual capability of JMJD1C may influence enhancer-promoter contacts crucial for the expression of key leukemic genes regulated by RUNX1. Our findings demonstrate a previously unappreciated role for the non-catalytic function of JMJD1C in transcriptional regulation, underlying a mechanism shared by different types of leukemias. Show less

Neurodevelopmental disorders (NDDs) exhibit complex genotype-phenotype associations that frequently result in inconclusive variant interpretations, contributing to suboptimal diagnostic yields (~ 40%). Koolen-de Vries syndrome (KdVS), an autosomal dominant NDD caused by KANSL1 haploinsufficiency, exemplifies this diagnostic challenge with its multisystem manifestations and lack of systematic genotype-phenotype associations. To address this gap, we constructed a comprehensive KdVS genotype-phenotype repository by systematically integrating all molecularly confirmed cases from global literature. Comprehensive phenotypic analysis revealed that core KdVS features include developmental delay/intellectual disability, characteristic craniofacial dysmorphism, hypotonia, and multisystem abnormalities. Phenotypic association analysis identified 249 significant correlations, demonstrating that KdVS clinical manifestations are highly interconnected rather than representing isolated features, such as the association between strabismus and hydrocephalus (OR = 14.26). Application of this repository to screen a Chinese rare disease cohort identified 53 KANSL1 variants. Among these, one de novo nonsense variant (NM₀₀₁₁₉₃₄₆₆.2: c.902T > G, p.Leu301Ter) was classified as pathogenic in a Chinese boy with classic KdVS features. The remaining 52 variants were categorized as variants of uncertain significance (VUS), approximately half of which were absent from gnomAD databases. Each VUS was comprehensively annotated with detailed clinical profiles to facilitate phenotype-driven reinterpretation. In conclusion, this study establishes KdVS as a highly interconnected multisystem disorder and demonstrates that deep phenotypic association analysis enhanced genetic diagnosis. This disease-specific repository approach provides a scalable framework for improving molecular diagnostics across rare NDDs. Show less

The molecular pathogenesis of lung adenocarcinoma (LUAD) involves genomic mutations, autophagy dysregulation, and signaling pathway disruptions. Autophagy, a key cellular process, is tightly linked to cancer development; genes like ATG5 and ATG10 influence lung cancer progression, and epigenetic regulators modulate autophagy-related carcinogenesis. However, the role of epigenetic-autophagy genes in LUAD's tumor microenvironment is under-researched. We used the "limma"" package to identify differential epigenetic-related genes associated with altered autophagy regulation (A-ERGs) in LUAD. Single-cell RNA sequencing was further employed to evaluate the heterogeneity of immune cells. Machine learning algorithms were utilized to construct and identify diagnostic markers for LUAD, which were then validated by receiver operating characteristic (ROC) curve analysis. Cell experiments, real-time PCR, and Western blot were conducted to verify the expression of KDM6B and KANSL1 and their effects on T-cell differentiation. Based on single-cell and transcriptome analyses, we screened 19 A-ERGs that were significantly differentially expressed in lung cancer tissues. These genes were primarily enriched in exhausted T cells. Subsequently, through machine learning, KDM6B and KANSL1 were identified to have excellent diagnostic performance. Single-cell level and transcriptome correlation analyses revealed that the expression of these two genes was associated with exhausted T cells. Results from In this study, we utilized bulk and single-cell transcriptomic data to uncover the potential molecular mechanisms of A-ERGs in lung cancer. We explored the characteristic distribution of these genes in the tumor immune microenvironment and identified two A-ERGs, KDM6B and KANSL1, as potential diagnostic biomarkers for lung adenocarcinoma (LUAD). Our findings offer novel strategies for targeted therapeutic interventions in LUAD. Show less

As global population aging intensifies, mental health issues in older adults are increasingly prominent, with depression being particularly prevalent and detrimental. The study investigated how substituting sedentary behavior (SB) and sleep (SLP) with physical activity (PA) affects depression risk in this population. Meta-analysis was conducted by searching four databases: PubMed, Scopus, SPORTdiscus, and PsycINFO (via EBSCOhost platform) for relevant studies published until January 2025. Regression coefficients (β) with 95% confidence intervals (CIs) for depressive symptoms were estimated. Publication bias was assessed using funnel plots and Egger's tests, and heterogeneity was evaluated using Q tests and the I Among 18,912 participants (53.45% female, ≥60 years) across nine studies, replacing SB with MVPA significantly reduced depression (β = -0.12, 95% CI: -0.20, -0.04), subgroup analyses indicated that reallocating 10, 30 and 60 min/day of SB to MVPA ( Substituting SB and SLP with MVPA is significantly associated with a reduction in depression, whereas no significant association is observed when replaced by LPA. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=546666, identifier CRD42024546666. Show less

To explore the latent categories of volume management behaviors in patients with chronic heart failure (CHF) and analyze their relationship with symptom distress. This cross-sectional study utilized a convenience sampling method to select 552 CHF patients from the cardiology departments of Nantong Sixth People's Hospital and Nantong Fourth People's Hospital. Volume management behaviors were assessed using the Volume Management Behavior Scale, and symptom distress was evaluated using the Symptom Distress Questionnaire (SDQ), which measures the severity of eight core symptoms. Latent Profile Analysis (LPA) was employed to identify behavioral categories. Multivariate Analysis of Variance (MANOVA) and multiple linear regression were used to analyze differences in symptom distress across behavioral categories and to examine the independent predictive effect of behavioral classification on symptom distress. The volume management behaviors of CHF patients were classified into three latent categories: active management type (43.1%), selective adherence type (27.7%), and passive dependence type (29.2%). Symptom distress scores showed a significant increasing trend across the three categories (active type: 10.5 ± 3.8; selective type: 13.2 ± 4.1; passive type: 16.3 ± 5.2, CHF patients exhibit three distinct clinical patterns of volume management behaviors, with the passive dependence type associated with the highest symptom burden. Behavioral category is a significant predictor of symptom distress. These findings provide an empirical basis for developing precise intervention strategies tailored to different behavioral phenotypes. Show less

The immunoregulatory effects of probiotics have been widely studied, particularly in maintaining immune balance. Conventional in vitro functional screening of probiotics relies on fresh donor-derived primary immune cells, which often exhibit significant inter-individual and temporal variability, limiting reproducibility and interpretation. As an alternative, human-induced pluripotent stem cell (iPSC)-derived dendritic cells were co-cultured with five probiotic strains in the current study to evaluate their immunomodulatory interactions. To assess whether cytokines produced by probiotic-stimulated dendritic cells can influence T cell differentiation, human CD4 Show less

Perimenopause is a critical turning point in women's life cycle, and the issue of sleep disturbance during perimenopause not only affects individual health, but also has profound implications for family functioning, socioeconomic status, and public health policies. Therefore, this study aims to explore different potential profiles of sleep quality in perimenopausal women in the community and analyze the influencing factors of different profiles. A cross-sectional study was conducted from July 2024 to December 2024, and a total of 281 perimenopausal women in the community were recruited from 4 communities in Bengbu by convenience sampling. The participants completed the pittsburgh sleep quality index (PSQI), and self-rating anxiety scale (SAS), self-rating depression scale (SDS) and simplified coping style questionnaire (SCSQ). Latent profile analysis(LPA) was employed to identify latent profiles of sleep quality of perimenopausal women in the community. The predictors of sleep quality in different latent profiles were assessed via multinomial logistic regression analysis. One-way ANOVA, chi-square test or Fisher exact test, and the Kruskal-Walis test were used to compare the PSQI scores of perimenopausal women in the community under different latent profile characteristics. The mean age of 281 perimenopausal women was 50.09 ± 5.08 years, and the prevalence of sleep disorders was 31.3%. The sleep quality of perimenopausal women in community could be divided into three different latent profiles: good sleep quality group (68.7%), falling sleep and maintenance difficulty group (24.2%), and poor sleep quality with sleep disorder group (7.1%). Taking the good sleep quality group as the reference group, drinking history (OR = 2.061), chronic disease history (OR = 2.154), spouse's health status (OR = 1.871) and anxiety (OR = 4.390) were the risk factors to predict the difficulty in falling asleep and maintaining sleep in community perimenopausal women (P < 0.05). Spouse's health status (OR = 2.139) and anxiety (OR = 19.029) were the risk factors for poor sleep quality and sleep disorders in community perimenopausal women (P < 0.05). There are three qualitatively different potential profile categories of sleep quality in perimenopausal women in the community, and drinking history, chronic disease, poor spouse health and anxiety have predictive effects on their profile categories. In the future, community nursing staff can take targeted interventions according to different categories of sleep quality in perimenopausal women to improve sleep quality and level of health promotion. Show less

Bidirectional intergenerational support is linked to late-life mental health, yet the underlying mechanisms remain unclear. Guided by intergenerational solidarity and social support theories, we examined how distinct support profiles relate to mental health among Chinese older adults, testing self-rated health (SRH) as a mediator and social participation as a moderator. We analyzed 7,843 adults aged ≥60 from the 2020 China Longitudinal Aging Social Survey. Latent profile analysis (LPA) identified bidirectional support profiles; group differences in mental health were assessed using the Bolck-Croon-Hagenaars (BCH) approach, followed by mediation and moderated-mediation models with bootstrap inference (5,000 resamples). Four profiles emerged-High Support-High Interaction-High Closeness (HS-HI-HC; 47.02%), Child-High Support-Low Interaction-High Closeness (CS-LI-HC; 33.46%), Moderate Support-Moderate Interaction-Low Closeness (MS-MI-LC; 10.37%), and Low Support-Low Interaction-Moderate Closeness (LS-LI-MC; 9.16%). Mental health differed across different profiles, with HS-HI-HC showing the best mental health levels (the lowest scores). SRH partially mediated these associations (for instance, HS-HI-HC indirect effect = -0.186, 95% CI -0.245 to -0.131). Social participation attenuated benefits of high family support but buffered risks under low support. Bidirectional intergenerational support is heterogeneous in China; profiles characterized by reciprocity and closeness show the most favorable mental health. SRH accounts for a modest but meaningful share of these associations, and social participation can substitute for-or amplify-the benefits of family support depending on profile. Findings inform profile-tailored community and family interventions to promote healthy aging. Show less

Objective To investigate the effect and mechanism of baicalin on blood lipid metabolism and immune function in rats with gestational diabetes mellitus (GDM). Methods Female rats fed with high-fat and high-sugar diet and male rats fed with ordinary diet were caged together to prepare pregnant rats, and the GDM rat model was established by intraperitoneal injection of streptozotocin (35 mg/kg). GDM rats were randomly divided into a model group, a fasudil (FA) (RhoA/RocK inhibitor) group (10 mg/kg), low-dose (100 mg/kg) and high-dose (200 mg/kg) baicalin groups, and a high-dose baicalin combined with LPA (RhoA/RocK activator) group (200 mg/kg baicalin+1 mg/kg LPA ), with 12 rats in each group. Another 12 pregnant rats fed with high-fat and high-sugar diet were selected as the control group. After 2 weeks of corresponding drug intervention in each group, the level of fasting blood glucose (FBG) was detected by blood glucose meter. The level of fasting insulin (FINS) in serum was detected by ELISA, and the insulin resistance index (HOMA-IR) was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) in serum, and the levels of immunomodulator tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-10 in peripheral blood were detected by the kit. The histopathological changes of liver were observed by HE staining. The proportion of T lymphocyte subsets in peripheral blood was detected by flow cytometry. The mRNA and protein expressions of Ras homolog gene family member A (RhoA), Rho associated coiled-coil forming protein kinase 1 (ROCK1), and ROCK2 in liver tissue were detected by real-time quantitative PCR and Western blot. Results Compared with the control group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8 Show less