Paraneoplastic syndromes arise when tumor-derived cytokines reprogram distant organs. Although mediators such as Interleukin-6 have been implicated, how these signals impair host organ function remain Show more
Paraneoplastic syndromes arise when tumor-derived cytokines reprogram distant organs. Although mediators such as Interleukin-6 have been implicated, how these signals impair host organ function remains incompletely defined. Here, we identify a cytokine-lipid axis that drives hepatic autophagy dysfunction. Specifically, in Show less
Lymphoplasmacytic Lymphoma (LPL) with immunoglobulin (Ig)A paraprotein is rare. When plasma cells dominate, the diagnosis becomes more challenging. We reported a case of a 71-year-old male with elevat Show more
Lymphoplasmacytic Lymphoma (LPL) with immunoglobulin (Ig)A paraprotein is rare. When plasma cells dominate, the diagnosis becomes more challenging. We reported a case of a 71-year-old male with elevated creatinine, splenomegaly, monoclonal IgA, and MYD88 mutation. Only monoclonal plasma cells were detected first, leading to a misdiagnosis of multiple myeloma. When progressive spleen enlargement was observed, re-evaluation revealed the emergence of monoclonal lymphocytes and the diagnosis was revised to LPL. The addition of rituximab to DVD regimen led to a partial response. For cases where an initial definitive diagnosis cannot be established, close follow-up is required for timely diagnosis revision and therapeutic adjustment. Show less
BackgroundSchatzker IV-C tibial plateau fractures pose a significant challenge for adequate visualization and reduction of the lateral articular surface through a solitary posteromedial (PM) approach. Show more
BackgroundSchatzker IV-C tibial plateau fractures pose a significant challenge for adequate visualization and reduction of the lateral articular surface through a solitary posteromedial (PM) approach. This study aimed to evaluate the effectiveness of an adjunctive lateral patellar ligament (LPL) approach in enhancing articular exposure, assessed through cadaveric modeling and a clinical case series.MethodsIn a cadaveric study, eight preserved knee specimens were dissected using a combined PM and LPL approach. The exposed articular area was quantitatively measured using calibrated digital imaging and ImageJ software before and after the LPL approach was established. Clinically, a case series of 10 patients with Schatzker IV-C fractures underwent open reduction and internal fixation via the combined approach between October 2021 and December 2023. Outcome measures included intraoperative exposure, 12-month postoperative Knee Society Score (KSS), and complications.ResultsThe addition of the LPL approach resulted in a 96% increase in the mean exposed articular area (from 8.4β―cmΒ² to 16.5β―cmΒ²; Show less
The current trial sought to assess the impact of fermented chicory root waste (FCRW) dietary administration on growth, lipid metabolism, chemical composition, and intestinal barrier pathway in common Show more
The current trial sought to assess the impact of fermented chicory root waste (FCRW) dietary administration on growth, lipid metabolism, chemical composition, and intestinal barrier pathway in common carp ( Show less
Oxidative deterioration of fish oil in aquafeeds poses a significant challenge to fish health and aquaculture sustainability, making it crucial to mitigate this issue through healthy and green nutriti Show more
Oxidative deterioration of fish oil in aquafeeds poses a significant challenge to fish health and aquaculture sustainability, making it crucial to mitigate this issue through healthy and green nutritional strategies. This study examined the potential of stevia chlorogenic acid (SCGA), a bioactive byproduct of stevia processing, to alleviate intestinal injury, gut microbiota dysbiosis, and lipid metabolism disorders induced by oxidized fish oil in turbot. Four diets with equal nitrogen and lipid contents were formulated: a control diet (PC) containing 5β―% fresh fish oil, an oxidized fish oil diet (OFO) comprising 5β―% oxidized fish oil, and two additional OFO diets supplemented with 200β―mg/kg (OFO200) or 400β―mg/kg (OFO400) of SCGA. Each dietary treatment was randomly assigned to three replicates, each containing 40 fish weighing approximately 16.99β―Β±β―0.01β―g, and administered over a 10-week period. Fish fed the OFO diet exhibited significantly compromised growth performance, as indicated by decreased WGR and SGR, along with reduced serum immune indices (IgM, C3, and C4) and lipid parameters (TC, HDL, LDL), and elevated serum D-LA levels (Pβ―<β―0.05). Moreover, dietary OFO markedly suppressed antioxidant enzyme activities (serum SOD; intestinal SOD, GSH-Px, and CAT) and elevated MDA concentrations (Pβ―<β―0.05). Additionally, OFO reduced intestinal expression of tight junction-associated genes (Claudin-4, Claudin-7, Occludin) while increasing expression levels of MLCK, Keap1, inflammatory mediators (IL-6, IL-1Ξ², TNF-Ξ±2, NF-ΞΊB, IFN-Ξ³), and Caspase7 (Pβ―<β―0.05). Notably, the TLR signaling pathway-related genes were upregulated, accompanied by pronounced shifts in gut microbiota composition (Pβ―<β―0.05). In hepatic tissue, lipogenesis-associated genes (FAS, ACC) were significantly increased, while key genes involved in lipid transport and Ξ²-oxidation (CD36, LPL, ACOX1, PPARΞ³) exhibited reduced expression (Pβ―<β―0.05). Dietary supplementation with 200 and 400β―mg/kg SCGA effectively mitigated these detrimental impacts. SCGA restored growth performance, serum immune parameters, and antioxidant enzyme activities to levels comparable to the PC group. It also normalized gene expression related to intestinal barrier function, inflammation, apoptosis, and hepatic lipid metabolism. Furthermore, SCGA supplementation modulated gut microbiota structure by increasing beneficial genera and decreasing potential pathogens. In conclusion, SCGA effectively improves growth performance, alleviates OFO-induced intestinal injury and microbial dysbiosis, and regulates lipid metabolism in turbot. These findings provide theoretical insights and technical support for the application of SCGA in aquaculture. Show less
Heat stress induces metabolic adaptations in fish, including the regulation of triglyceride (TG) synthesis/degradation to preserve cellular lipid balance and energy homeostasis. Diacylglycerol acyltra Show more
Heat stress induces metabolic adaptations in fish, including the regulation of triglyceride (TG) synthesis/degradation to preserve cellular lipid balance and energy homeostasis. Diacylglycerol acyltransferase (DGAT) catalyzes the final step in TG synthesis. However, the molecular mechanisms by which DGAT regulates TG metabolism in heat-stressed fish remain unexplored. Our previous study suggested that miR-10c regulates Show less
Hepatocellular carcinoma (HCC), as a cancer with high morbidity and mortality, urgently requires the development of a clinical prediction model with high robustness and generalizability and its progno Show more
Hepatocellular carcinoma (HCC), as a cancer with high morbidity and mortality, urgently requires the development of a clinical prediction model with high robustness and generalizability and its prognostic study of the tumor microenvironment to provide personalized clinical treatment for patients. Key prognostic genes were screened by analyzing mRNA expression data from GTEx and The Cancer Genome Atlas (TCGA) using limma difference analysis, Cox analysis, and machine learning (ML) algorithms. TCGA database was used as a training set, and the International Cancer Genome Consortium database was used as a test set to screen the best prognostic modeling algorithms using a combination of 101 ML algorithms for training and constructing Nomo score plots based on the algorithmic risk scores as well as Shiny online prediction models. Based on shapley additive explanations analysis, drug sensitivity analysis, and immune infiltration analysis were performed on the 6 genes screened to visualize the importance of prognostic genes. HCC tumor mutation load analysis was also performed. A risk prediction model for HCC death was developed based on the RSF algorithm, with an RSF model C-index of 0.765 and AUC values of 0.978, 0.989, and 0.964 for 1-, 3-, and 5-year ROC curves for the Nomo score model, respectively. LPL, RAET1E, RNASEH2A, GTF2H4, SCML2, and PRDM12 were potential diagnostic and prognostic markers, among which SCML2 and PRDM12 were significantly correlated with multiple drugs in drug sensitivity analysis.TP53 mutations were correlated with patients' age, chronological age, gender, histological tumor stage, T stage, and lymph node metastasis. An online HCC mortality risk prediction model was developed using the RSF algorithm. LPL, RAET1E, RNASEH2A, GTF2H4, SCML2, and PRDM12 are potential prognostic target genes, whereas TP53 mutations are associated with clinical features that may inform the development of HCC therapy. Show less
Lymphoplasmacytic lymphoma (LPL) represents a rare, indolent form of B-cell neoplasm, with non-immunoglobulin M subtypes, including the immunoglobulin G (IgG)-Ξ» variant, being notably uncommon. In thi Show more
Lymphoplasmacytic lymphoma (LPL) represents a rare, indolent form of B-cell neoplasm, with non-immunoglobulin M subtypes, including the immunoglobulin G (IgG)-Ξ» variant, being notably uncommon. In this report, we document a case of LPL distinguished by the presence of monoclonal IgG-Ξ» immunoglobulin and free Ξ» light chains, alongside its distinctive molecular characteristics and therapeutic outcomes. A 58-year-old male presented with fatigue, leukocytosis (75.45βΓβ109/L, 88.8% lymphocytes), lymphadenopathy, and splenomegaly. Serum studies detected an IgG-Ξ» monoclonal protein (6.74βg/L) with concurrent elevation of free Ξ» light chains. Bone marrow biopsy revealed marked hypercellularity, with lymphocytes comprising 80% of nucleated cells (predominantly plasmacytoid lymphocytes) and 5% plasma cell clusters. Genetic testing identified mutations in MYD88, CXCR4, and IGHV, along with trisomy 12 and del(13q14). He was diagnosed with LPL with IgG-Ξ» monoclonal immunoglobulin and free Ξ» light chains, classified as low risk per the Revised International Prognostic Scoring System. The patient received 3 cycles of bendamustine plus rituximab therapy. The blood cell count returned to normal and the spleen and lymph nodes were significantly reduced. Serum M protein levels decreased, and no obvious increase in B lymphocytes or plasma cells was found in the bone marrow. The patient achieved partial remission. This case highlights the diagnostic and therapeutic challenges associated with the IgG-Ξ» subtype of LPL, an uncommon variant of this rare malignancy. This report provides valuable insights into the clinical presentation, pathological features, molecular alterations, and treatment outcomes of this rare disease. Show less
Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide, particularly affecting young adults and elderly populations. This study investigates the neuroprotective po Show more
Traumatic brain injury (TBI) represents a major cause of mortality and disability worldwide, particularly affecting young adults and elderly populations. This study investigates the neuroprotective potential of orlistat (ORL), a gastrointestinal lipase inhibitor, in a murine TBI model. Behavioral, histological, and molecular analyses demonstrated that ORL significantly attenuated TBI-induced neurological damage. Microglial depletion experiments revealed that ORL's neuroprotective effects were largely mediated through microglial modulation. In vitro and in vivo studies showed that ORL suppressed microglial activation, phagocytosis, and migration. Single-cell RNA sequencing identified upregulation of lipoprotein lipase (LPL) in a TBI-induced microglial subpopulation. Molecular docking predicted ORL-LPL binding, suggesting direct enzymatic inhibition. Transcriptomic and metabolomic analyses further revealed ORL's modulation of microglial metabolic pathways and inflammatory responses. Our findings position ORL as a promising repurposed therapeutic for TBI through its novel mechanism of targeting microglial LPL-mediated neuroinflammation. Show less
Angiopoietin-like protein 3 (ANGPTL3) has emerged as an attractive therapeutic target for treating hyperlipidemia. Evinacumab, a monoclonal antibody targeting ANGPTL3, was approved by the FDA for homo Show more
Angiopoietin-like protein 3 (ANGPTL3) has emerged as an attractive therapeutic target for treating hyperlipidemia. Evinacumab, a monoclonal antibody targeting ANGPTL3, was approved by the FDA for homozygous familial hypercholesterolemia in 2021. Here, a series of novel sulfonamide scaffold ANGPTL3 modulators were designed and synthesized based on the structure-activity relationship (SAR) analysis. Among them, compound Show less
Sepsis is a severe systemic infection that can result in organ dysfunction and mortality. Dyslipidemia emerges as a key player in the intricate web of sepsis pathogenesis. Yet, the causal relationship Show more
Sepsis is a severe systemic infection that can result in organ dysfunction and mortality. Dyslipidemia emerges as a key player in the intricate web of sepsis pathogenesis. Yet, the causal relationship between blood lipid profiles and sepsis risk remains uncertain. This study aims to investigate the association between genetically predicted lipid traits, drug targets, and sepsis. The UK Biobank's Genome-wide association studies (GWAS) produced data on lipid and apolipoprotein characteristics. Four independent GWAS datasets were used to generate the sepsis statistics. The study utilized the two-sample Mendelian randomization (MR) approach, which incorporates multivariable (MVMR) models, to assess the correlations between sepsis risk and lipid-related parameters. To gain further insight, expression quantitative trait loci (eQTL) data were used to investigate the significant drug targets for lipid-lowering. Increasing ApoA-1 levels was associated with a diminished risk of sepsis (under 75) (OR 0.927, 95% CI 0.861-0.999; pβ=β0.047). This inverse correlation persevered even after performing multivariable MR. Elevated levels of HDL-C were associated with a decreased risk of sepsis (under 75) (OR 0.897, 95% CI 0.838-0.960; Pβ=β0.002) and incidence of sepsis (OR 0.883, 95% CI 0.820-0.951; Pβ=β0.001), which was consistent across sensitivity analyses. Furthermore, a decrease in total cholesterol exhibited a causal effect on sepsis in multivariable MR (OR 0.779, 95% CI 0.642-0.944; Pβ=β0.01). The genetic variants related to lowering LDL-C, located near the HMGCR and LDLR genes, were predicted to elevate the risk of sepsis. Moreover, genetic mimicry near the ANGPTL3 and LPL gene suggested that reducing the activity of ANGPTL3 and LPL (mimicking antisense anti-ANGPTL3 and LPL agents) was forecasted to decrease sepsis risk. Genetically inferred elevated ApoA-1, total cholesterol, and HDL-C manifest a protective effect against sepsis. Within the 9 lipid-lowering drug targets investigated ANGPTL3 and LPL exhibit potential as candidate drug targets for sepsis. Show less
1,3-dilinoleoyl-2-palmitoylglycerol (LPL) is an important structural lipid in breast milk fat, which plays an important role in the health of infants, and therefore the development of an efficient met Show more
1,3-dilinoleoyl-2-palmitoylglycerol (LPL) is an important structural lipid in breast milk fat, which plays an important role in the health of infants, and therefore the development of an efficient method for the preparation of such compounds is necessary. In the present study, LPL was efficiently catalytically synthesized by immobilized lipase ANL-MARE as a biocatalyst using tripalmitate and linoleic acid in a solvent-free system, and its digestive properties were investigated. The optimal process conditions for the enzymatic acidolysis of LPL were optimized by response surface test: the molar ratio of PPP:LA was 1:10, the enzyme addition was 13.60%, the reaction temperature was 50β, and the reaction time was 5 h. At this time, the relative content of LPL in the product was 67.78%, of which the relative content of sn-2 palmitic acid (sn-2 PA) accounted for 71.50%. In vitro gastrointestinal digestion of LPL resulted in the release of 59.69% of its fatty acids. The digested product contained higher levels of free unsaturated fatty acids and palmitic acid monoacylglycerols. In conclusion, the immobilized enzyme ANL-MARE has great potential to catalyze the preparation of LPL, which provides a new strategy and theoretical basis for the efficient preparation of human milk fat substitutes. Show less
Iodine is an essential micronutrient for developmental processes in the early stages; however, data on the effect of maternal iodine nutrition on milk lipids are limited. We aimed to explore the effec Show more
Iodine is an essential micronutrient for developmental processes in the early stages; however, data on the effect of maternal iodine nutrition on milk lipids are limited. We aimed to explore the effect of inadequate and excessive iodine intake on milk lipid metabolism and its mechanisms preliminarily. Rats were treated with different concentrations of potassium iodide water to construct animal models of iodine deficiency and excess. Iodine excess reduced serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels during lactation. Iodine deficiency had no significant effect on blood lipid indicators. In early and late lactation, iodine deficiency and excess inhibited triglyceride (TG) levels in milk; in mid-lactation, the inhibitory effect of iodine deficiency was attenuated. Under iodine deficiency and excess, the level of TG and the expression of THRΞ±1, THRΞ²1, ACC1, FAS, THRSP, BTN1A1, and ADFP proteins in the mammary gland were decreased during lactation; a decrease in LPL protein expression was observed in early and late lactation; and a decline of XOR protein expression was reported in mid and late lactation. Blood lipid metabolism was less sensitive to iodine deficiency during lactation. Iodine excess has a more profound effect on blood lipid metabolism, causing dyslipidemia in lactating rats. Long-term iodine deficiency and excess may have a negative role in the mechanisms regulating milk lipid synthesis and secretion by affecting thyroid hormones to inhibit the milk TG level. Show less
Xinyue Shen, Chaobin Qin, Zhixiang Wang+5 more Β· 2025 Β· FASEB journal : official publication of the Federation of American Societies for Experimental Biology Β· added 2026-04-24
The content and composition of milk fat are critical determinants influencing milk flavor, nutritional value, and economic significance. Buffalo milk is characterized by its high-fat content and compl Show more
The content and composition of milk fat are critical determinants influencing milk flavor, nutritional value, and economic significance. Buffalo milk is characterized by its high-fat content and complex lipid profile, characterized by elevated levels of health-beneficial fatty acids such as linoleic acid, Ξ±-linolenic acid, and arachidonic acid. However, the molecular regulatory mechanisms governing milk fat synthesis in buffaloes remain incompletely elucidated. This study employed transcriptomic analysis of milk fat globules (MFGs) from buffaloes exhibiting high and low milk fat content, identifying 15β949 annotated genes, including 234 differentially expressed genes (DEGs). Functional enrichment analysis revealed that these DEGs were predominantly associated with cell proliferation and differentiation, glyconeogenesis, and reproductive system development. Notably, the expression of IGFBP4, AGPAT4, GPAT3, GPR84, and PC exhibited positive correlations with buffalo milk fat content, identifying them as potential candidate genes regulating milk fat synthesis. Proteomic profiling identified 1678 proteins, including 53 differentially expressed proteins (DEPs). Enrichment analysis indicated that DEPs were primarily involved in nucleotide metabolism, the tricarboxylic acid (TCA) cycle, glycerophospholipid metabolism, and TGF-Ξ² signaling. Integrated analysis revealed potential interactions involving the IGFBP4 and PC genes, as well as the ACO1, TMED7, and APRT proteins, highlighting IGFBP4 as a pivotal regulator of milk fat synthesis. Functional validation demonstrated that overexpression or knockdown of IGFBP4 in buffalo mammary epithelial cells (BMECs) significantly modulated cell proliferation and altered the expression of key milk fat synthesis-related genes (FABP3, LPL, SCD, ACACA, and FASN), indicating that IGFBP4 can promote de novo fatty acid synthesis and intracellular lipid storage while inhibiting exogenous fatty acid uptake. Collectively, this study provides novel mechanistic insights into the regulation of milk fat synthesis in buffaloes and establishes a foundation for enhancing lactation traits through targeted genetic breeding strategies. Show less
The size of fat globules in ruminant milk to some extent affects the nutritional quality of dairy products and plays potential roles in infant and adult health. Lipid droplets (LD) in mammary epitheli Show more
The size of fat globules in ruminant milk to some extent affects the nutritional quality of dairy products and plays potential roles in infant and adult health. Lipid droplets (LD) in mammary epithelial cells are the precursors of milk fat globules (MFG). However, it is unclear what happens to proteins during the transformation process from LD to MFG, and little is known about the regulation of LD diameter in vivo. In this study, 12 mid-lactation Saanen dairy goats were randomly divided into 2 groups: a control group fed a basal diet and an experimental group fed a basal diet supplemented with CLA at 90 g/d. Goat milk was collected for analysis of composition and MFG size. Mammary gland tissue was collected for analysis of LD diameter and proteins. The size of MFG was found to depend on LD diameter in the mammary glands of dairy goats. The regression equations for MFG size (Y) and LD diameter (x) were Y Show less
Quinolinic acid (QA) is a metabolite of tryptophan catabolism involved in the biosynthesis of nicotinamide adenine dinucleotide (NAD). It has been extensively studied in the context of neuropsychiatri Show more
Quinolinic acid (QA) is a metabolite of tryptophan catabolism involved in the biosynthesis of nicotinamide adenine dinucleotide (NAD). It has been extensively studied in the context of neuropsychiatric disorders in the past decades. Recent studies have also linked high plasma QA levels to obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) and diabetes. In the present study, we have explored the impact of long-term oral QA administration on glucose and lipid metabolism in mice. We observed a protective role for QA in preventing hepatic lipid accumulation in high-fat-diet fed mice, whereas oral administration of NAD showed opposite effects. We further demonstrated that QA reduces hepatic lipid uptake by inhibiting the expression of lipoprotein lipase (LPL) and fatty acid translocase (CD36) in liver, thereby mitigating liver lipid accumulation in the context of a high-fat diet. Our data suggest that QA is an important regulator of lipid homeostasis and has potential as a therapeutic target for MASLD. Show less
Reading relies on the ability to map written symbols with speech sounds. A specific part of the left ventral occipitotemporal cortex, known as the Visual Word Form Area (VWFA), plays a crucial role in Show more
Reading relies on the ability to map written symbols with speech sounds. A specific part of the left ventral occipitotemporal cortex, known as the Visual Word Form Area (VWFA), plays a crucial role in this process. Through the automatization of the mapping ability, this area progressively becomes specialized in written word recognition. Yet, despite its key role in reading, the area also responds to speech. This observation raises questions about the actual nature of neural representations encoded in the VWFA and, therefore, the underlying mechanism of the cross-modal responses. Here, we addressed this issue by applying fine-grained analyses of within- and cross-modal repetition suppression effects (RSEs) and Multi-Voxel Pattern Analyses in fMRI and sEEG experiments. Convergent evidence across analysis methods and protocols showed significant RSEs and successful decoding in both within-modal visual and auditory conditions, suggesting that populations of neurons within the VWFA distinctively encode written and spoken language. This functional organization of neural populations enables the area to respond to both written and spoken inputs. The finding opens further discussions on how the human brain may be prepared and adapted for an acquisition of a complex ability such as reading. Show less
The transcription factor MafF is a novel regulator of adipogenesis, but its role in hepatic steatosis remains unclear. This study aimed to explore the impact of MafF on hepatocyte steatosis and its un Show more
The transcription factor MafF is a novel regulator of adipogenesis, but its role in hepatic steatosis remains unclear. This study aimed to explore the impact of MafF on hepatocyte steatosis and its underlying mechanisms. A stable MafF-overexpressing cell line was established using lentiviral infection. RT-qPCR and Western blot analysis confirmed MafF expression. Free fatty acid (FFA) or ethanol (ETOH) induction was used to simulate hepatocyte steatosis in non-alcoholic or alcoholic fatty liver disease (NAFLD or AFLD). Cell activity and lipid accumulation were assessed through the CCK-8 assay, Calcein-AM/PI staining, and Oil Red O staining. The changes in lipid metabolism-related gene expression before and after FFA or ETOH treatment were detected using RT-qPCR. FFA or ETOH induced lipid accumulation in hepatocytes, and overexpression of MafF significantly ameliorated ETOH-induced hepatocyte steatosis but had little effect on FFA-induced hepatocyte steatosis. MafF overexpression significantly reduced the expression of peroxisome proliferator-activated receptor gamma (PPARG), acetyl-CoA carboxylase (ACC), and lipoprotein lipase (LPL) in hepatocytes. Upon FFA induction, control (NC) cells exhibited downregulation of these genes, whereas MafF-overexpressing cells upregulated LPL expression. In contrast, under ETOH treatment, NC cells upregulated these genes, while MafF-overexpressing cells showed downregulation. This study highlighted the regulation of lipid-related genes by MafF, including PPARG, ACC, and LPL, and its effect on FFA- and ETOH-induced hepatocellular lipid accumulation in distinct ways. MafF showed a more pronounced improvement in ETOH-induced hepatocyte steatosis, providing crucial insights into MafF's role in hepatic lipid metabolism and potential therapeutic strategies for NAFLD and AFLD. Show less
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to u Show more
Integration of human genomics and other omics across different ancestries provides novel, affordable, and systematic approach for target identification. We used Mendelian randomization approaches to unravel causal associations between 2,940 circulating proteins and 19 CVD. We found 218 proteins that impacted risk of one or more CVDs through forward MR (106 and 182 using cis-pQTLs only and cis- + trans-pQTLs, respectively), among which 107 were previously reported as associated with CVD or CVD-related traits. There were 102 proteins replicated (FDR < 5%, 53 with cis-pQTLs only and 88 with cis- + trans-pQTLs) using the FinnGen Olink data. BTN3A2 was highlighted as a novel candidate gene for ischemic stroke, suggesting a crosstalk between immune modulation and stroke pathogenesis. Single cell integration prioritized PAM for stable angina pectoris and ventricular arrhythmia and LPL for peripheral artery disease, whose transcriptional expressions were enriched in cardiomyocytes. Forward and reverse MR found largely non-overlapping proteins (only 2 overlapped: LGALS4 and MMP12), suggesting distinct proteomic causes and consequences of CVD. Our study provides human genetics-based evidence of novel candidate genes, a foundational step towards full-scale causal human biology-based drug discovery for CVD. Show less
Chemokines and neutrophil extracellular trap formation (NETosis) are critical drivers of inflammatory responses. However, the molecular characteristics and interaction mechanisms of these processes in Show more
Chemokines and neutrophil extracellular trap formation (NETosis) are critical drivers of inflammatory responses. However, the molecular characteristics and interaction mechanisms of these processes in sarcopenia remain incompletely understood. Utilizing the mRNA expression profile dataset GSE226151 (including 19 sarcopenia, 19 pre-sarcopenia, and 20 healthy control samples), enrichment analysis was performed to identify differentially expressed NETosis-related genes (DENRGs) and chemokine-related genes (DECRGs). Two machine learning algorithms and univariate analysis were integrated to screen signature genes, which were subsequently used to construct diagnostic nomogram models for sarcopenia. Single-gene Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were used to investigate pathway associations, followed by the construction of a gene interaction network. A total of 7 DECRGs and DENRGs were identified, primarily enriched in chemokine signaling pathways, cytokine-cytokine receptor interactions, and sarcopenia-related diseases. Machine learning and univariate analysis revealed three signature genes (CXCR1, CXCR2, and LPL). The nomogram models demonstrated high predictive accuracy in distinguishing sarcopenia from both healthy and pre-sarcopenic states, as evidenced by AUC values of 0.837 (95% CI 0.703-0.947) and 0.903 (95% CI 0.789-0.989), respectively. Single-gene GSEA highlighted significant associations between these genes and the JAK-STAT and PPAR signaling pathways. GSVA indicated that sarcopenia was closely linked to upregulated chemokine signaling, cytokine-receptor interaction activities, and leukocyte transendothelial migration. The research pinpointed three genes associated with chemokines and NETosis (CXCR1, CXCR2, LPL) and developed highly accurate diagnostic models, offering a new and preliminary approach to differentiate sarcopenia and its early stages. Show less
Mitochondrial oxidative stress plays a critical role in cancer development and progression. However, there is limited research on the relationship between mitochondrial oxidative stress and liver hepa Show more
Mitochondrial oxidative stress plays a critical role in cancer development and progression. However, there is limited research on the relationship between mitochondrial oxidative stress and liver hepatocellular carcinoma (LIHC). Mitochondrial oxidative stress-related genes were collected from Genecards Portal. Prognosis-linked genes (PLGs) were identified by univariate Cox regression analysis. A risk model was constructed based on the PLGs using least absolute shrinkage and selection operator (LASSO) analysis. Receiver operating characteristic (ROC) curves were used to determine the predictive ability of the model. The expression levels of the prognostic genes were verified in the cell lines. Cell proliferation, apoptosis, and invasion assays were conducted to investigate the functional role of the target gene. We constructed a novel risk model based on 9 prognostic genes (CYP2C19, CASQ2, LPL, TXNRD1, CACNA1S, SLC6A3, OXTR, BIRC5, and MMP1). Survival analysis showed that patients with a low-risk score had a much better overall survival (OS). Prognostic risk score was found to be an independent predictor of prognosis. Patients in the high-risk group had a less favorable tumor microenvironment characterized by a lower degree of immune cell infiltration. Among the nine prognostic genes, MMP1, identified as the most promising candidate, demonstrated the capacity to enhance tumor cell proliferation and invasion. Our investigation reveals the oncogenic role of mitochondrial oxidative stress in LIHC. For the first time, we established a risk prediction model for mitochondrial oxidative stress in patients with LIHC. MMP1 has the potential to function as a promising biomarker in LIHC. Show less
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. Ho Show more
Lanthanides-doped luminescent materials have gathered considerable attention due to their application potential in stress sensing, lighting and display, anti-counterfeiting technology and so forth. However, existing materials mainly cover the 380-1540βnm range, with slight extension to the UV region, impeding their applications in solar-blind imaging, background-free tracking, concealed communication, etc. To address this challenge, here we propose guidelines for far-UVC (200-230βnm) optical design. Accordingly, we achieve multi-stimulated far-UVC luminescence at ~222βnm in Pr Show less
The color of rice leaves are important agronomic traits that directly influence the proportion of sunlight energy utilization and ultimately affect the yield and quality, so it is crucial to excavate Show more
The color of rice leaves are important agronomic traits that directly influence the proportion of sunlight energy utilization and ultimately affect the yield and quality, so it is crucial to excavate the mechanism of regulating rice leave color. To investigate the molecular mechanism that triggers the purple color in rice leaf, phenotypic characterization and genome-wide transcriptome analysis were conducted using the japonica rice cultivar nipponbare (Nip) and its two purple leaf mutants, A total of 2247, 5484, 4525, 2103, 4375 and7029DEGs (differentially expressed genes) were identified in nip-a vs These results not only revealed the molecular mechanism triggering leaf purple color in the rice mutants Show less
This study was conducted to investigate the effects of replacing fish meal with either whole-fat or defatted krill powder on the growth, body color, immunity, and related gene expression of red-white Show more
This study was conducted to investigate the effects of replacing fish meal with either whole-fat or defatted krill powder on the growth, body color, immunity, and related gene expression of red-white koi carp. A total of 630 red-white koi carp with an initial body mass of 13.5 Β± 0.05 g were randomly divided into seven groups with three replicates per group and 30 fish per replicate. The control group was fed a basic diet (C0). The other six diets were supplemented with different levels of whole krill meal or defatted krill meal as replacements (10% whole fat, 20% whole fat, 30% whole fat, 10% defatted, 20% defatted, and 30% defatted) in the experimental groups, named W10, W20, W30, D10, D20, and D30, respectively, for a total duration of 60 days. The growth, body color, immunity and gene expression indexes were measured in the koi after completion. The results indicate the following. (1) Compared with C0, the experimental groups of koi showed a significant increase in the specific growth rate (SGR) ( Show less
Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are persistent environmental contaminants linked to adverse health effects, Show more
Per- and polyfluoroalkyl substances (PFAS), particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are persistent environmental contaminants linked to adverse health effects, including an increased risk of breast cancer. However, the molecular mechanisms through which PFAS contribute to breast cancer development remain poorly understood. In this study, we employed an integrated approach combining network toxicology, single-cell sequencing, spatial transcriptomics, and molecular simulation to investigate the effects of PFAS on breast cancer. By constructing a protein-protein interaction (PPI) network, we identified six core genes (PPARG, CD36, FABP4, PPARGC1A, LPL, and PCK1) that play a significant role in the development of breast cancer. These genes are involved in key cellular processes such as lipid metabolism, oxidative phosphorylation, and immune regulation, all of which are disrupted by PFAS exposure. Single-cell and spatial transcriptomic analyses revealed that these genes are predominantly expressed in endothelial, myeloid, and cancer-associated fibroblasts within the tumor microenvironment. Molecular simulation further confirmed strong binding energies between PFAS and these target proteins, suggesting direct interactions. Our findings provide novel insights into how PFAS may promote breast cancer progression at the molecular level and highlight the need for further research on environmental pollutants in cancer risk assessment and public health initiatives. Show less
Follicular development is tightly regulated by the coordinated action of multiple hormones and complex gene regulatory networks in granulosa cells, which play a crucial role in egg production and fert Show more
Follicular development is tightly regulated by the coordinated action of multiple hormones and complex gene regulatory networks in granulosa cells, which play a crucial role in egg production and fertility in hens. Extensive studies have established that Niemann-Pick C2 (NPC2) is a key regulator of cholesterol metabolism and steroid hormone secretion in mammals. However, its specific role in chicken ovarian granulosa cells remains unclear. In this study, cultured chicken ovarian granulosa cells were used to investigate the function of NPC2 through transfection with NPC2 overexpression vectors or small interfering RNAs (siRNAs). The results showed that silencing NPC2 significantly increased the expression of SREBP1, SREBP2, LPL, SCD1, CPT1 and DGAT2 genes involved in lipid synthesis (P < 0.01), and also increased the synthesis of Triglyceride (TG) and Cholesterol (TC) in granulosa cells (P < 0.05), whereas NPC2 overexpression led to a marked reduction in the expression of these indicators of lipid metabolism (P < 0.01). Furthermore, NPC2 knockdown significantly inhibited the production of progesterone (P Show less
Membrane lipids play a crucial role in brain function and cell signalling, and they serve as key biological substrates in inflammatory responses, thrombosis, and energy metabolism. Multiple clinical a Show more
Membrane lipids play a crucial role in brain function and cell signalling, and they serve as key biological substrates in inflammatory responses, thrombosis, and energy metabolism. Multiple clinical and molecular evidences suggest that membrane lipids are probably involved in the pathogenesis of ischemic stroke (IS). However, current knowledge about the membrane lipid landscape and its involvement in IS pathophysiology is limited. We performed untargeted lipidomic analysis on erythrocyte membranes from 56 IS patients and 55 healthy controls. Integrated with gene expression and weighted gene co-expression network analysis, we identified dysregulated lipid signalling pathways and their contributions to IS pathophysiology. A total of 1392 erythrocyte membrane lipids were detected and quantified. Our results revealed significant impairment of membrane lipid homeostasis in IS patients, characterized by a marked reduction in glycerophospholipids (GPLs) and lysophospholipids (LPLs). Further analysis indicated that the impaired lipids were primarily concentrated in three disturbed signalling pathways, including the phospholipase A2-mediated GPL-LPL pathway, the phospholipase C-mediated inositol 1,4,5-trisphosphate/diglyceride pathway, and the sphingosine-1-phosphate (S1P)-S1P receptors pathway. Gene expression results indicated that these pathways were inhibited during the subacute phase of IS. Furthermore, these lipid signalling pathways form a highly interconnected network that collaboratively contributes to inflammation and thrombosis in IS, thereby influencing the progression and prognosis of the disease. Our findings reveal impaired erythrocyte membrane lipid homeostasis in IS, which implicates inflammatory processes and thrombosis in IS. This research offers new insights into the role of membrane lipids in IS pathogenesis, potentially informing future monitoring and therapeutic strategies. Show less
Intramuscular fat (IMF) content in beef cattle is a critical determinant of beef meat quality, as it positively influences juiciness, tenderness, and palatability. In China, the crossbreeding of Wagyu Show more
Intramuscular fat (IMF) content in beef cattle is a critical determinant of beef meat quality, as it positively influences juiciness, tenderness, and palatability. In China, the crossbreeding of Wagyu and Angus is a prevalent method for achieving a better marbling level. However, the molecular mechanisms governing IMF regulation in these crossbreeds remain poorly understood. To elucidate the mechanism of IMF deposition in these crossbred cattle, we conducted a comparative transcriptomic analysis of Show less
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that are widely found in organisms and play an important regulatory role in various biological processes, especially immune and infla Show more
MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs that are widely found in organisms and play an important regulatory role in various biological processes, especially immune and inflammatory responses. However, the function of miR-320b in the inflammatory responses of bovine mammary epithelial cells (bMECs) remains to be elucidated. In this study, we examined the miR-320b mimic transduction group (miR-320b_mimic) and negative control mimic transduction group (NC_mimic) of lipopolysaccharide-treated bMECs using data-independent acquisition (DIA) proteomics and untargeted metabolomics. Subsequently, we performed a joint analysis of the sequencing data. Proteomic analysis identified 330 differentially abundant proteins (DAPs) primarily related to PPAR, ferroptosis, arachidonic acid metabolism, IL-17, and complement and coagulation cascades. Metabolome analysis identified 128 and 66 differentially accumulated metabolites (DAMs) in the positive and negative ion mode primarily involved in linoleic acid metabolism, cholesterol metabolism, AMPK, MAPK, and chemokine. Integrated metabolomics and proteomics analysis revealed the co-enrichment of DAPs and DAMs in choline metabolism in cancer, endocrine resistance, glycerophospholipid metabolism, primary bile acid biosynthesis, and the ferroptosis signaling pathways. The results of quantitative real-time PCR (RT-qPCR) showed that compared with the NC_mimic group, mRNA expression levels of COX-2, IL-12Β A, iNOS, MAPK1, and MAPK14 genes were significantly down-regulated, and the mRNA expression levels of PPARΞ³, CEBPΞ±, CEBPΞ², FABP4, and LPL genes were significantly up-regulated in the miR-320b_mimic group. These results provide crucial insights into the molecular regulatory functions of miR-320b and offer valuable data for further research on molecular breeding aimed at enhancing mastitis resistance in bovine animals. Show less
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatom Show more
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatomical structures of the midfoot and Lisfranc joint complexes. A total of 100 adult lower limbs were dissected and the types of LPL were divided according to their insertions, among them, 63 were (63%) and 37 were female (37%); 50 were on the left side (50%) and 50 were on the right side (50%). The fiber bundle length, origin width, insertion width, and thickness of the LPL were measured. (1) According to the insertions of the LPL, they were divided into: β Type I, the LPL was inserted at the base of the second metatarsal (M2) in 47 cases; β‘ Type II, the LPL was inserted at the base of M2 and fused with tibialis posterior tendon (TPT) in 16 cases; β’ Type III, the LPL was absent in 16 cases; β£ Type IV, the LPL was inserted at TPT in 6 cases; β€ Type V, the LPL was inserted at the intermediate cuneiform (IC) in 1 case; β₯ Type VI, bifid LPL with one bundle inserted at the base of M2, and the other bundle inserted at the medial cuneiform (MC) in 4 cases; β¦ Type VII, two bundles of LPL inserted at the base of M2 in 8 cases; β§ Type VIII, the LPL consisted of 3 bundles; the distal, middle and proximal bundles was inserted at the base of M2, the TPT and the lateral side of navicular bone in 2 cases, respectively. (2) There was a statistical significance in the length of LPL between male (31.62βΒ±β3.83) mm and female (28.07βΒ±β3.46) mm (t=-3.050, Pβ=β0.003). There was no statistical significance in the types of LPL between male and female (Z=-1.721, Pβ>β0.05), and no statistical significance in the types between left and right sides (Z=-0.026, Pβ>β0.05). According to our research, LPL originates from M5 and is divided into 8 types according to its insertion location, of which insertion at the base of M2 is the most common. In addition, we found that LPL has fibrous fusion with the long plantar ligament and the TPT, which may be involved in maintaining arch stability. The classification of LPL in this study is a supplement to the anatomical structure of the middle foot and Lisfranc joint complex, providing a new direction for the diagnosis and treatment of middle foot and arch injury in the future. Show less