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The rising demand for high-quality pork among consumers has driven interest in genetic improvement strategies. Crossbreeding is well known to influence carcass performance and meat quality; however, the molecular mechanisms underlying these effects are still poorly understood. In this study, the F1 generation of the Songlei Crossbred Pig (SL) was developed through crossing the Songliao Black Pig (male) (SS) and the Leixiang Pig (female) (LL). We integrated the transcriptomes and metabolomes of the longissimus dorsi (LD) muscle of SS and SL under identical conditions to identify key mechanisms regulating the quality of crossbred meat. Compared with those of SS, the slaughter weight, carcass weight, and dressing percentage of SL were significantly lower, but the backfat thickness was greater; however, meat quality traits, including intramuscular fat (IMF), colour, and pH The meat quality of SL was better than that of their male parents, but not the carcass traits were not. Additionally, several critical genes and pathways related to lipid metabolism were identified. These findings provide new insights into how meat quality can be improved by hybridization. Show less

Drug chemoresistance remains a major reason of treatment failure in cancer patients. In head and neck squamous cell carcinoma (HNSCC), the seventh most common cancer worldwide, cisplatin chemotherapy remains the gold standard for advanced tumors but often faces loss of responsiveness and the drawback of relapse. We previously showed that the metabolic and angiogenic factor angiopoietin-like 4 (ANGPTL4) is a molecular biomarker of oral dysplasia and HNSCC. We also found that through interaction with Neuropilin 1 (NRP1), ANGPTL4 activates proliferative and migratory pathways that contribute to HNSCC development. Using HNSCC xenografts, patient tumor-derived organoids, tumor spheroids, and HNSCC cell lines, CAL27, HN13, and HN4, here we provide evidence of the role of ANGPTL4 in the development of platinum-based chemoresistance in HNSCC through the promotion of DNA damage response (DDR) and homologous recombination (HR). ANGPTL4 enhanced these mechanisms by promoting phosphorylation of RAD51 recombinase in Tyr Show less

To observe the effect of acupuncture on astrocyte activation following cerebral ischemia-reperfusion injury (CIRI) Transcriptome and single-cell sequencing were used to analyse gene expression in middle cerebral artery occlusion (MCAO)-induced rats. Acupuncture was applied at Baihui (GV20) and Dazhui (GV14) for 7 d. The infarct volume was assessed CIRI activated p38 MAPK signaling, increased the expression of A1 markers (GFAP and C3), and proinflammatory cytokines, and decreased the expression of the A2 marker S100A10. Acupuncture inhibited p38 phosphorylation, upregulated MSK1, reduced C3 and inflammatory cytokines, increased S100A10 expression, decreased infarct volume, and improved neurological function. Acupuncture protects against ischemic stroke by targeting the p38 MAPK/MSK1 pathway. It inhibits p38 MAPK phosphorylation and activates MSK1, thereby promoting a shift in astrocyte polarization from the pro-inflammatory A1 to the reparative A2 type, as reflected by decreased C3 and increased S100A10 expression. This shift reduces pro-inflammatory cytokines, alleviates cerebral inflammation, and promotes neural repair, ultimately diminishing infarct volume, restoring neurons, and improving behavior. These findings elucidate the mechanism of acupuncture and support its clinical use. Show less

Reliable prediction of reproductive toxicity remains a critical challenge in drug development and environmental safety. Here, a biomarker-integrated, fluorescent reporter-based reproductive organ-on-a-chip platform that recapitulates the multicellular composition, 3D architecture, endocrine signaling, and cyclic dynamics of the human menstrual cycle, is presented. The system is constructed using primary human theca, granulosa, endometrial stromal and stem cells, vascular endothelial cells, uterine macrophages, and myometrial smooth muscle cells, compartmentalized within collagen-hyaluronic acid hydrogels. Early-response toxicity biomarkers-ANGPTL4 (ovary) and SERPINB2 (endometrium)-are genetically linked to mCherry or GFP fluorescent reporters, enabling real-time, cell-type-specific visualization of toxicant-induced stress. Transcriptomic profiling, KEGG pathway enrichment, and gene knockdown studies confirm ANGPTL4 and SERPINB2 as functional mediators of toxic injury, not just passive indicators. Upon exposure to dioxin and other reproductive toxicants, the platform shows strong, region-specific fluorescent responses that preceded changes detected by conventional cytotoxicity assays. This system demonstrates high sensitivity, temporal precision, and mechanistic insight, offering a scalable and physiologically relevant tool for high-content reproductive toxicology screening. Furthermore, it supports endocrine crosstalk between the ovary and uterus, and dynamic responses across the menstrual cycle, enabling future applications in personalized toxicity prediction and preclinical safety evaluation. Show less

Bladder cancer continues to represent a considerable global health burden, characterized by increasing incidence and mortality rates. Despite its prevalence as one of the most common urological malignancies, diagnosis remains challenging due to the scarcity of dependable, non-invasive biomarkers. Consequently, the imperative to identify novel biomarkers for effective diagnosis becomes evident. This study included 101 hospital patients, whose were stratified according to biopsy-confirmed histopathological diagnosis into the bladder cancer group (n=69) and the non-cancer group (n=32). Serum angiopoietin-like 4 (ANGPTL4) concentrations were quantified using an enzyme-linked immunosorbent assay (ELISA). Significantly lower serum ANGPTL4 levels (approximately 28% lower) were observed in the bladder cancer cohort compared to the non-cancer group (p=0.043). The optimal cut-off value was 16.95 ng/ml, yielding a sensitivity of 74% and a specificity of 53%. The Youden Index was established at 0.2704. The presented findings indicate that ANGPTL4 poorly differentiates patients with bladder cancer from non-cancer patients. Show less

Previous studies have illuminated a significant genetic component in motor neuron disease (MND) pathogenesis, with several causative genes identified. However, a substantial proportion of MND cases remain genetically unexplained, particularly regarding the comprehensive contribution of rare, high-impact variants across the exome. Leveraging whole-exome sequencing data from nearly half a million UK Biobank participants, we systematically investigated the association between high-confidence protein-truncating variants (HC PTVs) and MND risk in a Caucasian subset. Our large-scale gene-based association analysis utilized REGENIE software and LOFTEE-defined HC PTVs. We identified significant preliminary associations between HC PTVs in 14 genes and an increased risk of MND. Notably, while NEK1 has been previously implicated in ALS, the remaining 13 genes ( These findings suggest a potential expansion of the known genetic landscape of MND, and highlight novel biological pathways implicated in its pathogenesis. This study underscores the power of large-scale population genetics in uncovering critical disease mechanisms and offers new avenues for mechanistic research and therapeutic development for MND, pending independent validation. Show less

There is a strong correlation between delayed diagnosis and high mortality rate in pulmonary arterial hypertension (PAH). Recent research indicates that circular RNAs (circRNAs) may serve as potential diagnostic biomarkers for PAH. This study aimed to identify important circRNAs associated with PAH to support early diagnosis and explore possible key disease mechanisms. GSE171827 and GSE113439 were obtained from the Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (DECs) and genes (DEGs). MicroRNAs (miRNAs) related to PAH were obtained from the Human microRNA Disease Database (HMDD). We validated changes in DEC expression levels using RT-qPCR in hypoxia- and normoxic-induced human pulmonary artery endothelial cells. Then, the potential relationship between DEC expression levels and mean pulmonary artery pressure (mPAP) in PAH patients was investigated. Finally, bioinformatics analyses were performed to construct a competing endogenous RNA (ceRNA) network and excavate the potential functions of DECs. Only hsa_circ₀₀₀₅₆₂₃ expression was significantly downregulated in PAH. Low hsa_circ₀₀₀₅₆₂₃ expression levels in the plasma of PAH patients were significantly associated with mPAP ( Show less

Atherosclerosis, a progressive inflammatory disease and the leading cause of cardiovascular disease (CVD), remains a global health burden due to the lack of effective early therapeutic interventions. Although growing evidence highlights the involvement of plasma proteins in atherogenesis, their causal contributions to disease pathogenesis are poorly understood. To address this gap, we conducted a proteome-wide Mendelian randomization (MR) analysis using cis-pQTLs (cis-protein quantitative trait loci) from the deCODE and UKB-PPP cohorts (~90,000 individuals) as instrumental variables. We integrated colocalization analysis, summary-data-based MR (SMR), and HEIDI tests to systematically prioritize causal plasma proteins. Key findings were replicated in the CARDIOGRAMplusC4D (coronary artery disease, CAD) and FinnGen (CVD) cohorts. Functional validation was performed through phenome-wide association studies (PheWAS), single-cell transcriptomics, histological staining, and ELISA assays to characterize protein expression patterns in specific cell types and tissues. Among 2,711 plasma proteins analyzed, 28 showed strong genetic associations with atherosclerosis. Of these, five proteins (ADK, ANGPTL4, CD4, MGAT1, SYT11) met strict validation criteria through colocalization (posterior probability of colocalization, PP.H4 > 0.8) and SMR. Subsequent replication using MR and PheWAS further confirmed the causal roles of ADK, CALB2, and COMT in CAD and other CVD outcomes. Notably, CALB2 was specifically enriched in mast cells within atherosclerotic plaques and adipose tissue, and plasma levels were significantly elevated in patients with severe carotid artery stenosis (CAS). This study identifies 28 novel therapeutic targets for atherosclerosis using a rigorous multi-omics approach. Our findings establish CALB2 as a promising biomarker and therapeutic target, particularly in severe CAS, by linking genetic evidence to cell-type-specific expression and clinical phenotypes. These insights pave the way for precision medicine approaches in the prevention and treatment of CVD. The online version contains supplementary material available at 10.1186/s12967-025-07269-6. Show less

Lung cancer (LC) is the most prevalent form of malignant neoplasm globally, as well as the major cause of cancer-related death. Identifying effective pharmaceutical targets is paramount in advancing the development of treatment modalities for LC. Protein-wide Mendelian randomization (MR) was used in this study. The present study collated data on plasma proteins from a protein quantitative trait loci (pQTL) study with a total of 4907 individuals. Genetic associations with LC were obtained from GWAS, including 3791 cases and 489012 controls. Integration of pQTL and LC genome-wide association study (GWAS) data was employed to identify candidate proteins. MR used single nucleotide polymorphisms (SNPs) as a genetic tool to estimate the causal effect of exposure on the outcome, while reverse Mendelian randomization was performed to assess the presence of false positives. The present study utilized these approaches to evaluate the causal relationship between plasma proteins and LC. Finally, protein-protein interaction (PPI) and functional enrichment analyses were performed to illustrate potential links between proteins and current LC drugs. Finally, drug prediction and molecular docking were performed to predict drugs and explored the expression distribution of key genes by single-cell sequencing. We identified 46 plasma proteins that are strongly associated with LC Fifteen of these proteins have protective effects. Among them, MMP8(OR = 0.87, 95%CI:0.78-0.97, p = 0.013) had the most significant protective effect. In contrast, 31 proteins increased the risk of LC. IL36A༈OR = 1.20, 95%CI:1.041-1.38, p = 0.012) exhibited the most significant MR result. Notably, COL2A1, MMP19 showed reverse causality. This was further verified by enrichment analysis, which confirmed the causal effect of these proteins. Additionally, the researchers utilized the DSigDB database to predict potentially effective intervening drugs, identifying nine possible candidates. Molecular docking showed that the drugs bind very much to the proteins. KDR and ANGPTL4 are abundantly expressed in lung tissue and are differentially expressed between cells. The present study has revealed six potential drug targets for the treatment of LC. Drugs designed to target these proteins will be more likely to attain success in clinical trials and are expected to assist in the development of LC drugs and reduce drug development costs. Show less

Increasing epidemiological studies suggested that maternal exposure to fine particulate matter (PM This study aimed to investigate PM In the present study, we first identified that angiopoietin-like 4 (ANGPTL4), sirtuin 3 (SIRT3), and D2-hydroxyglutarate (D2-HG) may be potential biomarkers for PM These findings suggested that PM Show less

The selective peroxisome proliferator-activated receptor delta (PPARD) agonist seladelpar reduces liver injury and modulates bile acid metabolism in preclinical models. Seladelpar was recently approved for the secondary treatment of primary biliary cholangitis (PBC). Despite its beneficial effects for liver diseases, the target cells of seladelpar on a single-cell level remain unknown. This study is aimed at investigating the effect of seladelpar on single liver cells. CD-1 mice were gavaged with vehicle or seladelpar (10 mg/kg body weight), and the liver was harvested 6 h later. Single-nuclei RNA sequencing (snRNA-seq) analysis showed the engagement of PPARD target genes primarily in hepatocytes and cholangiocytes by seladelpar. The top two upregulated genes, The selective PPARD agonist seladelpar induced PPARD-responsive genes primarily in hepatocytes and cholangiocytes. Seladelpar upregulated Show less

Atherosclerotic cardiovascular disease treatment is being reevaluated, since a residual cardiovascular risk (RCR) persists even in patients who achieve optimal LDL-C values. Underlying causes are metabolic dysfunction, lipoprotein(a), inflammation, and triglyceride-rich lipoproteins and their remnants. Dietary treatment options like time-restricted eating (TRE) are becoming more widely acknowledged for their potential advantages in metabolic health and weight control, as a treatment of atherosclerosis expanding beyond LDL-C medication. Beyond weight loss, TRE (which restricts meals to a window of 6 to 8 h) appears as the most accessible treatment, and has been shown to improve blood pressure, lipid profiles, and glucose regulation through mechanisms like metabolic switching and circadian synchronization. We hypothesize, and will present our arguments, that a key mechanism underlying the cardiovascular and weight-related benefits of TRE is its impact on the circadian regulation of angiopoietin-like protein 4 (ANGPTL4) activity within adipose tissue. Additionally, lipolysis is accelerated by ANGPTL4 activation. TRE, via its actions on ANGPTL4, therefore not only inhibits adipose fatty acid uptake but stimulates their release as well. Additionally, TRE may increase intravascular very low-density lipoprotein (VLDL) catabolism by muscle due to the reduced exposure of lipoprotein lipase (LPL) to competing chylomicrons, known to slow the rate of VLDL catabolism. During the prolonged fasting, VLDL residence time is thus shortened, limiting the exposure to endothelium and hepatic lipases and thus reducing the amount of atherogenic remnant particles. Larger, longer-term randomized controlled studies in a variety of groups are required to further clarify TRE's function in RCR prevention and therapy. As knowledge of triglyceride lipoprotein (TRL) metabolism expands, a comprehensive strategy for the management of RCR emerges, and a broader spectrum of LPL regulator-based therapeutics is created. Consequently, it is advisable to prioritize further research into the influence of TRE on LPL modulation via ANGPTL4 and ANGPTL8, which provides a natural, accessible, and low-cost alternative. Show less

In their recent study, Zeng et al. (2025) employed single-cell RNA sequencing to delineate the landscape of spinal cord injury (SCI), highlighting a previously underappreciated communicative role for endothelial tip cells in engaging astrocytes and macrophages. While their work provides a valuable resource and generates compelling hypotheses, it also opens several critical avenues that demand immediate scrutiny. This Letter offers a prospective outlook and a critical examination of their findings. We argue that the computationally predicted paracrine networks, such as the Angptl4-Sdc4 axis identified by the authors, require rigorous in vivo functional validation to establish causality. Furthermore, the current snapshot data lack the temporal and spatial resolution necessary to decipher the dynamics of these interactions. Most importantly, we explore the therapeutic dilemma of targeting tip cells-a strategy that must delicately balance their detrimental signaling roles against their indispensable function in revascularization. Addressing these challenges is paramount to transforming these descriptive insights into mechanistic understanding and viable therapeutic strategies for SCI. PRE-REGISTERED CLINICAL TRIAL NUMBER: Not applicable. Show less

The heterogeneity of the tumor immune microenvironment (TIME) and therapeutic resistance in Colorectal cancer (CRC) present substantial clinical challenges. In this study, 1136 CRC samples from TCGA and GEO were utilized for the overall research design, and tumor subtype classification (Immunity_High and Immunity_Low) was specifically performed on the TCGA cohort (n = 568) using single-sample gene set enrichment analysis (ssGSEA) and t-SNE dimensionality reduction; t-SNE was selected because the study focused on distinguishing local clustering features of immune subtypes-it excels in enhancing sample aggregation within subtypes and highlighting local differences, which aligns with classification needs, so UMAP (prioritizing global structure preservation) was not used. The GEO cohort (n = 568) was used for subsequent validation of the prognostic model and results. A 12-gene prognostic model, comprising ANGPTL4, FABP4, RBP7, and 9 additional non-core genes (CCL22, NOS2, TGFB3, APOD, CHGB, CX3CL1, APOBEC3F, LCN12, BST2), was developed using Least Absolute Shrinkage and Selection Operator-Cox regression (LASSO-Cox regression) regression.The functions of the core genes and potential therapeutic candidates were investigated via single-cell sequencing, molecular docking, dynamics simulations, drug sensitivity analysis, Human Protein Atlas (HPA) and quantitative Real - time Polymerase Chain Reaction (qPCR). The Immunity_High subtype, characterized by the presence of CD8 This multi-omics study integrates multi-omics data to elucidate the immune-metabolic heterogeneity in CRC, establishing a precise prognostic model and providing bioinformatic evidence for key roles of ANGPTL4, FABP4, and RBP7 in the tumor microenvironment, thereby suggesting novel strategies to overcome immunotherapy resistance. Show less

Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with increasing evidence implicating the oral microbiome and tumor microenvironment in its progression. However, the mechanistic impact of OSCC patient-derived saliva on tumor development remains poorly understood. We established an orthotopic OSCC mouse model and topically applied saliva collected from OSCC patients to assess its effects on tumor progression. Multi-omics analyses, including 16 S rRNA sequencing, tumor transcriptomics (RNA-seq), and metabolomics (LC-MS), were performed to explore changes in the oral microbiota, gene expression profiles, and metabolic pathways. Treatment with OSCC patient saliva significantly accelerated tumor growth compared to controls. Saliva application altered the oral microbiota, most notably causing a significant enrichment of the genus Staphylococcus. Tumor transcriptomics revealed upregulation of genes associated with chronic neutrophilic inflammation (Mpo), cancer-associated fibroblast (CAF) activation, and extracellular matrix (ECM) remodeling (Angptl4, Col2a1). Metabolomic analysis demonstrated profound metabolic reprogramming within the tumors, including enhanced amino acid metabolism (tryptophan, glutamate), fatty acid oxidation, and accumulation of the oncometabolite succinate. Integrated analysis showed that Staphylococcus abundance was strongly correlated with these inflammatory and metabolic signatures. This study demonstrates that saliva from OSCC patients promotes tumor progression in vivo through a multifactorial mechanism involving inflammation, stromal remodeling, and metabolic rewiring. These findings highlight the tumor-promoting potential of salivary and microbial components, suggesting new avenues for diagnostic and therapeutic strategies targeting the oral microenvironment in OSCC. Show less

Osteosarcoma demonstrates limited responsiveness to PD-1 blockade, largely due to its immunosuppressive tumor microenvironment (TME). The specific mechanisms by which cancer-associated fibroblasts (CAFs) contribute to immunosuppression in osteosarcoma are not fully understood. We performed single-cell RNA sequencing (scRNA-seq) on osteosarcoma tissues from patients treated with neoadjuvant chemotherapy and anti-PD-1 therapy to investigate the tumor microenvironment. Cellular composition, gene expression programs, and signaling pathways were analyzed. Functional assays, pull-down and PLA-flow binding validation, and in vivo mouse models were used to dissect the mechanisms by which CAF-derived factors influence CD8⁺ T cell function and contribute to immunotherapy response. We identified a subpopulation of CD36⁺ CAFs, characterized by adaptive uptake of oxidized low-density lipoprotein (OxLDL) and activation of the PPARG-FABP4 axis. This metabolic program promoted ANGPTL4 secretion, which bound integrin on CD8⁺ T cells and activated the JAK2-STAT3 pathway, leading to T cell exhaustion and impaired effector function. In vivo, administration of VitE effectively scavenged OxLDL, reprogrammed the TME, enhanced CD8⁺ T cell infiltration, and synergized with PD-1 blockade to improve tumor control. CD36⁺ CAFs drive immunosuppressive metabolic reprogramming via the OxLDL-PPARG-ANGPTL4 axis, promoting CD8⁺ T cell exhaustion and resistance to immunotherapy in osteosarcoma. Targeting this pathway with VitE alleviated CAF-mediated immune suppression and enhanced PD-1 blockade responses in preclinical models, providing a rationale for metabolism-based combinatorial strategies in osteosarcoma. Show less

Statins have provided the first line treatment for hypercholesterolemia for over two decades with the addition of ezetimibe if low-density lipoprotein (LDL) cholesterol targets are not achieved with statins alone. However, treatment with statins and other oral small molecules is often insufficient to attain the target levels of LDL cholesterol. This review describes the monoclonal antibodies (mAbs) that have been produced to overcome the residual cardiovascular risk related to uncontrolled LDL cholesterol. In recent years the mAbs, alirocumab and evolocumab, targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have become established worldwide as an additional treatment for patients not achieving LDL cholesterol goals on statins and ezetimibe, or sometimes as an alternative treatment in those with statin intolerance. They have been shown to be safe and effective in reducing cardiovascular events in patients at high cardiovascular risk. More recently, four new mAbs targeting PCSK9 have been developed and approved in China. Some of these mAbs offer the benefit of less frequent subcutaneous dosing and some are humanized mAbs and it remains to be seen whether their efficacy will be retained with long term use. New drug targets were identified to potentially reduce elevated triglyceride levels and the mAb angiopoietin-like 3 (ANGPTL3) inhibitor, evinacumab, was found to be effective in reducing LDL cholesterol in patients with homozygous familial hypercholesterolemia (FH) and has been approved for that indication. SHR-1918 is another mAb targeting ANGPTL3 being developed in China which may also be effective to treat homozygous FH. These drugs are expensive and may not be suitable for a wider indication and there are antisense oligonucleotides and small interfering RNA treatments in development which may prove more cost effective. Another mAb at an early stage of development is MAR001 targeting angiopoietin-like 4 (ANGPTL4). The role for this remains to be established. Show less

Infantile hemangioma (IH) is a common benign vascular tumor in infants, often requiring intervention due to potential functional impairment and cosmetic concerns. Propranolol, a nonselective β-adrenergic receptor blocker, is the first-line therapy for IH, yet its mechanisms remain incompletely elucidated. This prospective study investigated the systemic angiogenic protein profile changes in response to propranolol in 14 treatment-naïve IH infants compared to 14 healthy controls using antibody array analysis. We identified twenty-six angiogenic proteins significantly downregulated in pretreatment IH patients compared to healthy controls. After 3 months of propranolol treatment, six proteins including HB-EGF, TGFα, ANGPTL4, Follistatin, Tie-1 and PLGF were significantly upregulated. Bioinformatic enrichment analysis revealed that these proteins are involved in key biological processes and signaling pathways, including epithelial cell proliferation, angiogenesis regulation, VEGF signaling, ERBB-EGFR axis, Ras-MAPK, and PI3K-Akt pathways. These results suggest that propranolol treatment is associated with a rebalancing of dysregulated angiogenic proteins in IH, through modulating both pro- and anti-angiogenic factors to rebalance vascular homeostasis. Our study provides novel insights into the systems-level pharmacological actions of propranolol and proposes potential biomarkers for treatment response evaluation. Show less

This study aims to explore the plastic changes in cell lineages during the progression of osteoarthritis (OA) and their relationship with dysregulation of signaling pathways and provide new molecular targets for precise treatment. Single-cell RNA sequencing (scRNA-seq) technology was utilized to perform high-resolution cell lineage analysis of OA patients. The mappings of distinct cell subpopulations were systematically constructed and revealed the changes in key cell types and their transformation trajectories throughout the progression of OA. Furthermore, KEGG and GO enrichment and pseudotime trajectory analysis were applied to elucidate the functional reprogramming of different cell types and the dynamic imbalance of their signaling networks in OA. Additionally, in vitro experiments were conducted to validate the biological functions of candidate genes in OA. Articular cartilage showed a transcriptional cellular heterogeneity in OA by scRNA-seq analysis; the annotated PreFC, FC, and PreHTC subsets accounted for the main part of OA samples. PreFC cells revealed transcription, signaling, and metabolic reprogramming in OA; pseudotime trajectory found that PreFC transformed to FC cells under the condition of hypoxia and metabolic reprogramming, while fibrosis and ECM degradation pathways showed intense upregulation in preHTC evolved from PreFC cells. HIF1A and ANGPTL4 were identified as key molecular regulators of OA progression, contributing to ECM degradation, inflammation, and apoptosis in chondrocytes, as confirmed through functional validation. The cellular trajectories of OA show significant plasticity changes which are influenced by the dysregulation of multiple signaling pathways. This research provides new insights into the pathological process of OA and offers potential targets for therapeutic strategies targeting these abnormal mechanisms. Show less

Lactylation, a recently identified post-translational modification, plays a critical role in tumor progression and immune regulation. However, its cellular heterogeneity and functional impact in lung adenocarcinoma (LUAD) remain poorly understood. This study was designed as exploratory biological research to characterize lactylation-associated patterns at the single-cell level and to propose a potential lactylation-related prognostic model. Single-cell transcriptomic data from LUAD and normal lung tissues were analyzed to quantify lactylation activity using AUCell based on 332 lactylation-related genes. Cell-cell communication was inferred using CellChat to identify ligand-receptor interactions among subpopulations. Candidate genes were selected by integrating ligand-receptor pair genes, marker genes from highly lactylated subtypes, and previously reported lactylation-related genes. A total of 101 machine learning model combinations were evaluated to construct the prognostic model. Selected genes were further validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the potential relationship between Lactylation activity was higher in tumor epithelial and stromal cells, with particularly elevated levels in specific epithelial subpopulations. A 12-gene signature was identified, comprising nine risk genes (e.g., This study presents a lactylation-based prognostic model for LUAD and uncovers potential immune-related mechanisms by which highly lactylated epithelial cells may contribute to immune evasion and tumor progression. Show less

Bariatric surgery is the most effective way to treat obesity and improves obesity-related comorbidities. Laparoscopic sleeve gastrectomy (LSG) is one of several standard procedures, laparoscopic greater curvature plication (LGCP) is a relatively alternative bariatric technique, and Roux-en-Y gastric bypass (RYGB) is the gold standard of bariatric surgical procedures. The study included 95 patients who underwent three types of bariatric surgery. 48 of the subjects (28 women, 20 men) underwent LSG, 35 of the patients (21 women, 14 men) underwent LGCP and 12 of the subjects (8 women, 4 men) underwent RYGB. Anthropometry and biochemical parameters (glucose, glycated hemoglobin, cholesterol, HDL and LDL cholesterol, triglycerides, adiponectin, leptin, ANGPTL3, ANGPTL4, ApoD, ApoE, FGF19, and FGF21) were determined before and after 3, 6, 12 and 18 months of surgeries. All types of bariatric surgeries markedly decreased body weight, BMI, and percentage of body fat. The surgical procedures resulted in a decrease in mean fasting glucose, triglycerides, glycated hemoglobin concentrations and leptin concentrations in blood serum. On the other hand, plasma concentrations of adiponectin increased significantly. Different results were observed in serum ANGPTL3, ANGPTL4, ApoD, ApoE, FGF19, and FGF21 levels after all surgeries. All three types of bariatric surgery resulted in significant weight loss and changes in the levels of the measured parameters. Key words Bariatric surgery " Adipokines " FGF19 " FGF21 " ANGPTL. Show less

Lung squamous cell carcinoma (LUSC) is a leading cause of cancer-related mortality. Although immunotherapy has recently demonstrated clinical benefits, the biological roles of immune-related genes (IRGs) in LUSC remain insufficiently understood. In this study, transcriptomic and clinical data from 493 LUSC patients were obtained from The Cancer Genome Atlas (TCGA). IRGs were identified through weighted gene co-expression network analysis, followed by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression to screen for prognostic genes and establish a risk prediction model. The model's predictive performance was validated, and the immune landscape associated with distinct risk subgroups was systematically characterized. Expression patterns and clinical significance of the signature genes were further investigated using bioinformatics analysis, quantitative real-time PCR, Western blotting, and immunohistochemistry. A total of 55 differentially expressed IRGs were identified, among which 8 genes ( This study establishes a novel IRGs-based prognostic signature with potential utility for risk stratification and individualized immunotherapeutic strategies in LUSC. Furthermore, it also provides valuable insights into the role of Show less