👤 Yang Xiao

The protein branched-chain ketoacid dehydrogenase kinase (BCKDK), which regulates the metabolism of branched-chain amino acids, has recently been implicated in tumor progression. However, the role of BCKDK in lung cancer remains largely unexplored. In this study, we explored the mechanisms by which BCKDK influences lung cancer progression and contributes to drug resistance. By integrating single-cell RNA and bulk RNA sequencing data from lung cancer patients, we identified BCKDK as a novel gene related to malignant epithelial cells, involved in tumor initiation and associated with poor patient prognosis. Subsequently, through a series of molecular biology experiments, we demonstrated that BCKDK promotes aerobic glycolysis, Trametinib resistance, and tumor progression in lung cancer by upregulating MYC transcription. Mechanistically, BCKDK interacts with BCLAF1 to promote its phosphorylation at the serine 285 site. This modification facilitates BCLAF1 binding to the MYC promoter, thereby enhancing MYC transcription. Subsequently, elevated MYC levels upregulate hexokinase 2, promoting aerobic glycolysis and lung cancer progression. In addition, the elevated glycolysis product, lactate, promotes Trametinib resistance by upregulating the ABC transporters. Taken together, our data identify BCKDK as a novel regulator of aerobic glycolysis that promotes lung cancer progression and Trametinib resistance through the BCKDK/BCLAF1/MYC/HK2 axis. Targeting BCKDK in combination with Trametinib may offer a promising treatment for lung cancer. Graphical representation of the BCKDK/BCLAF1/MYC/HK2 axis and its role in Trametinib resistance and lung cancer progression. Created with BioRender.com. Show less

Neuroblastoma (NB) is the most common solid tumor in children, characterized by high recurrence rates, drug resistance, and significant mortality. In this study, we analyzed the proteomic profiles of NB tissue samples alongside other pathological categories, including ganglioneuroma (GN) and ganglioneuroblastoma (GNB). Using weighted gene co-expression network analysis (WGCNA), the core prognostic gene models associated with histopathology of NB were identified. Furthermore, by mapping our core prognostic gene models onto drug-perturbed transcriptome profiles from the L1000FWD and CMap databases, repurposing drug candidates were screened and validated for NB. Our proteomic analysis reveals that pathways associated with the cell cycle and DNA replication are significantly upregulated in NB, while oxidative phosphorylation, pyruvate metabolism, and the TCA cycle are notably downregulated compared to GNB and GN. By applying WGCNA, we identified a core prognostic gene model strongly associated with the unfavorable subtype and high MKI of NB and primarily related to chromatin binding and mRNA metabolic process. Protein-protein interaction network analysis identified 15 hub genes in this core prognostic module: SMARCA4, SMARCA5, SMARCC2, SMARCC1, PBRM1, BRD3, ARID1A, BRD2, ARID1B, KDM1A, TP53BP1, ALYREF, CBX1, SF3B1, and ADNP, which mainly related to chromatin remodeling. Notably, SMARCA4 and ALYREF are also high-risk genes of mortality and validated as potential prognostic biomarkers for NB. Through repurposing drugs screening, mocetinostat and clofarabine were validated as effective treatments in two NB cell lines. Mocetinostat and clofarabine offer valuable insights for the development of novel targeted therapies in neuroblastoma. Show less

Clinical guidelines recommend the use of statins to reduce portal pressure and alleviate portal hypertension (PH). However, there is a lack of population-level studies on the use of non-statin Low-Density Lipoprotein Cholesterol (LDL-c) reduction agents for the treatment of PH. This study utilized a novel method, Mendelian Randomization (MR) analysis, to investigate the impact of commonly used LDL-c-lowering medications on PH. Instrumental variables (IVs) for eight lipid-lowering drug-related genes were extracted from three large-scale LDL-c databases of Genome-Wide Association Studies (GWAS), followed by MR analysis. The MR results indicated that, compared to normal individuals, lower expression of CETP and NPC1L1 in whole blood (result of meta-analysis: CETP [OR: 0.322, 95%CI:0.130-0.795, P = 1.396e-02], NPC1L1 [OR: 0.057, 95%CI: 0.022-0.146, P = 2.670e-09]) is associated with reduced portal pressure. The IVs of target genes were subjected to MR analysis with coronary atherosclerosis (CAD) as a positive control, confirming that the IVs can effectively substitute for the biological function of the target gene, thereby further enhancing the reliability of the results. Subsequently, Summary-based Mendelian Randomization (SMR) analysis was conducted by using expression quantitative trait loci (eQTL) data to validate the results of the MR analysis. The SMR results suggested that only NPC1L1 is associated with PH (OR: 0.648, 95%CI: 0.472-0.891, P Show less

DHX36 is an ATP-dependent DNA/RNA helicase that unwinds the guanine-quadruplexes (G4s) of DNA or RNA and regulates their metabolism for key biological functions. Breast cancer is a malignant tumor and effective targeted therapy drugs are limited, even though chemotherapy is generally used. In this study, we found that overexpression of DHX36 promotes breast cancer cell growth, migration, and invasion in vitro, while knocking down or knocking out reversed in vitro and in vivo. Moreover, DHX36 was highly expressed in most clinical breast tumor tissues compared with the matched healthy tissues. Accordingly, higher DHX36 expression correlated with poor recurrence-free survival (RFS) in the patients of breast cancer. These results substantiate that DHX36 might be a diagnostic and prognostic biomarker and is a proto-oncogene that promotes the growth and metastasis of breast cancer. Thus, targeting DHX36-associated G4s in genes, particularly in proto-oncogenes, might be a novel anticancer strategy. Show less

Discs large homolog 2 (DLG2) has been implicated in cancer development, yet its role in cervical cancer remains unclear. This study aims to explore the regulatory mechanism of DLG2 in cervical cancer and its clinical implications. Quantitative reverse transcription polymerase chain reaction and western blotting assays were employed to detect RNA and protein expression, respectively. Colony formation assay, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, and transwell assays were conducted for cell functional analysis. A xenograft mouse model assay was performed to analyze tumor tumorigenesis in vivo. m6A RNA immunoprecipitation assay was used to analyze the association of METTL3 and DLG2. DLG2 was underexpressed in cervical cancer tissues and cells. Elevating DLG2 levels significantly suppressed cervical cancer cell proliferation, migration, and invasion, while promoting apoptosis. Additionally, DLG2 overexpression led to the deactivation of the Hippo/YAP signaling pathway. In vivo, DLG2 overexpression was shown to reduce tumor formation. We also discovered that METTL3 destabilized DLG2 mRNA through an m6A-dependent mechanism. Moreover, lowering DLG2 expression mitigated the effects of METTL3 silencing on cervical cancer cell malignancy. DLG2 acted as a tumor suppressor in cervical cancer by inhibiting the Hippo/YAP signaling pathway. The METTL3-dependent regulation of DLG2 mRNA stability could be a critical factor in cervical cancer progression. Show less

Brain-derived neurotrophic factor (BDNF) protects neurons from degeneration, making it a promising therapeutic target for Alzheimer's disease (AD). However, the genetic regulation resulting from BDNF overexpression in the brain remains to be further illustrated. Using APP/PS1 and rTg4510 mouse models, we analyzed hippocampal transcriptomes after intrahippocampal AAVT42- Show less

Cervical cancer remains one of the leading causes of cancer-related deaths among women globally, and there is still a need to research molecular targets that can be used for prognosis assessment and personalized molecular therapies. Here, we investigate the role of potential molecular target ribosomal L22-like 1 (RPL22L1) on cervical cancer, identify its potential mechanisms, and explore its related applications in prognosis and molecular therapies. Multiple cervical cancer cohorts online, tissue microarrays and clinical tissue specimens were analyzed for the association between RPL22L1 expression and patient outcomes. Functional and molecular biology studies of cell and mice models were used to clarify the effects and potential mechanisms of RPL22L1 on cervical cancer. RPL22L1 is highly expressed in both cervical adenocarcinoma and squamous cell carcinoma, and its expression is significantly associated with histology grade, clinical stage, recurrence, vascular space involvement, tumor sizes and poor prognosis. In vitro and in vivo experiment revealed that RPL22L1 overexpression significantly promoted cervical cancer cell proliferation, migration, invasion, tumorigenicity and Sorafenib resistance, which were attenuated by RPL22L1 knockdown. Mechanistically, RPL22L1 competitively binds to ERK phosphatase DUSP6, leading to excessive activation of ERK. The combined application of ERK inhibitors can effectively inhibit RPL22L1 overexpressing cervical cancer cells both in vivo and in vitro. RPL22L1 promotes malignant biological behavior of cervical cancer cells by competitively binding with DUSP6, thereby activating the ERK pathway. The combined use of Sorafenib and an ERK inhibitor is a potentially effective molecular targeted therapy for RPL22L1-high cervical cancer. Show less

Men, despite having a lower likelihood of longevity compared to women, generally exhibit better health status when they achieve longevity. The role of DNA methylation in this paradox remains unclear. We performed whole-genome bisulfite sequencing on long-lived men (LLMs), long-lived women (LLWs), younger men (YMs) and younger women (YWs) to explore specific methylation characteristics in LLMs. Despite an accelerated methylation aging rate in LLMs compared to LLWs, we identify thousands of differentially methylated genomic units (DMUs) in LLMs independent of age and sex. These DMUs, validated by an elastic net classifier, can serve as methylation markers for discriminating longevity potential in men. Many are located near health-related genes. Genes like PIWIL1 and EXT1, with promoters featuring DMUs, exemplify the potential role of LLM-specific methylation patterns in suppressing age-related diseases by regulating gene transcription. Our findings provide evidence of a distinct methylation feature contributing to healthy aging and longevity of LLMs. Show less

Fatty acyl desaturases (Fads) are known to play critical roles in the biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs) in fish species. To date, research on Fads in fish has predominantly focused on Fads2, while studies on Fads1 have been rarely reported. Acipenseriformes, commonly known as Chondrostei, are an ancient fish lineage with unique evolutionary history. However, the biological roles and evolutionary status of Fads1 in Chondrostei remain unclear, which constrains our understanding of the evolutionary processes shaping LC-PUFA biosynthesis in this lineage. In this study, we identified and characterized a fads1 gene from Chinese sturgeon (Acipenser sinensis), a critically endangered Chondrostei, using molecular cloning and multiple bioinformatic analyses. The spatio-temporal expression patterns, functional characteristics, and transcriptional regulation in response to dietary fatty acids were investigated. The coding sequence of the fads1 gene was 1317 bp in length, encoding a protein of 438 amino acids. Bioinformatic analyses suggested high conservation of fads genes across Chondrostei despite their complex evolutionary history. Functional characterization in yeast showed that Chinese sturgeon Fads1 exhibited Δ5 desaturation activity, efficiently converting 20:3n-6 to arachidonic acid (ARA) and 20:4n-3 to eicosapentaenoic acid (EPA). Fatty acid composition analysis indicated that Chinese sturgeon could biosynthesize LC-PUFAs when they are deficient in their diets. Taken together, these results suggest that fads1 plays a crucial role in LC-PUFA biosynthesis in Chinese sturgeon, which provides solid theoretical basis for dietary LC-PUFA requirement of Chinese sturgeon. Furthermore, our findings provide novel insights into evolutionary diversification of fads genes in fish species. Show less

The mitogen-activated protein kinase (MAPK) signaling pathway plays roles in cell proliferation, differentiation, and apoptosis, all crucial for cellular transformation. It's no surprise that MAPK alterations are prevalent in numerous tumors. Several critical genes in the MAPK signaling pathway, including Show less

Hair follicle stem cells (HFSCs) are resident stem cells within hair follicles (HFs) that possess self-renewal and differentiation capacities, serving as a critical model for regenerative medicine research. Their dynamic interaction with dermal papilla cells (DPCs) plays a decisive role in HF development and cycling. Show less

Osimertinib (OSI) therapy, a cornerstone in treating non-small cell lung cancer (NSCLC), has been severely limited by rapidly developing acquired resistance. Inhibition of bypass activation using a combination strategy holds promise in overcoming this resistance. Biguanides, with excellent anti-tumor effects, have recently attracted much attention for this potential. The current study investigated whether novel biguanide compounds developed by our team could overcome OSI resistance and the underlying mechanisms were explored. A comprehensive screening assay using OSI-resistant cells identified the optimal combination of biguanide compounds with OSI. Proteomics, co-immunoprecipitation mass spectrometry, RNA sequencing, and homologous recombination assays were used to elucidate the molecular mechanisms underlying combination therapy. NSCLC tumor tissues, especially OSI-resistant tissues, obtained from our clinic were used to assess the correlations between key proteins and OSI resistance. SMK-010, a highly potent biguanide compound, effectively overcame OSI resistance These findings highlight the crucial role of the BMI1/FGFR1 axis in OSI resistance and provide a rational basis for the future clinical application of the biguanide, SMK-010, in combination with OSI. 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

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is a leading cause of cancer-related mortality worldwide. Despite its high mortality rate, the development of effective targeted therapies remains challenging due to an incomplete understanding of their underlying molecular mechanisms. Here, we highlight a pivotal role for IL27/IL27RA signalling in driving HCC progression. Our findings reveal that IL27RA is significantly upregulated in HCC. Both in vitro and in vivo experiments demonstrated that IL27RA knockdown markedly inhibited the proliferation and metastasis of HCC cells. Mechanistic investigations show that IL27RA promotes HCC progression through activation of the STAT3/TGF-β signalling pathway. Specifically, STAT3 enhances TGFβR1 protein stability by increasing the transcription of USP15. Notably, IL27RA regulates the proliferation and metastatic potential of liver cancer cells in a TGFβR1-dependent manner. In summary, these results underscore the critical role of IL27RA in HCC progression, identifying it as a promising therapeutic target for HCC treatment. Show less

Interleukin-27 (IL-27) is a cytokine that is reported to be highly expressed in the peripheral blood of patients with pulmonary tuberculosis (PTB). IL-27-mediated signaling pathways, which exhibit anti- Mycobacterium tuberculosis (Mtb) properties, have also been demonstrated in macrophages infected with Mtb. However, the exact mechanism remains unclear. This study aimed to clarify the potential molecular mechanisms through which IL-27 enhances macrophage resistance to Mtb infection. Both normal and PTB patients provided bronchoalveolar lavage fluid (BALF). Peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals and stimulated with 50 ng/mL macrophage-colony stimulating factor (M-CSF) to obtain monocyte-derived macrophages (MDMs). Using 100 ng/mL phorbol 12-myristate 13-acetate (PMA), THP-1 cells were induced to differentiate into THP-1-derived macrophage-like cells (TDMs). Both MDMs and TDMs were subsequently infected with the Mtb strain H37Rv and treated with 50 ng/mL IL-27 prior to infection. The damage and inflammation of macrophages were examined using flow cytometry, enzyme-linked immunosorbent assay (ELISA), and Western blotting. Patients with PTB had elevated levels of IL-27 in their BALF. Preconditioning with IL-27 was shown to reduce H37Rv-induced MDMs and TDMs apoptosis while also decreasing the levels of Cleaved Caspase-3, Bax and the proinflammatory cytokines TNF-α, IL-1β, and IL-6, promoting the expression of Bcl-2 and the anti-inflammatory factors IL-10 and IL-4. Silencing of the IL-27 receptor IL-27Ra increased macrophage damage and inflammation triggered by H37Rv. Mechanistically, IL-27 activates autophagy by inhibiting TLR4/NF-κB signaling and activating the PI3K/AKT signaling pathway, thereby inhibiting H37Rv-induced macrophage apoptosis and the inflammatory response. Our study suggests that IL-27 alleviates H37Rv-induced macrophage injury and the inflammatory response by activating autophagy and that IL-27 may be a new target for the treatment of PTB. Show less

Gastric cancer (GC) is a common malignant tumor, which originated from the epithelial cells of the stomach. It has the characteristics of high incidence and poor prognosis. Therefore, it is urgent to find new prognostic markers for the diagnosis and treatment of GC. Download gene expression matrix and clinical data from TCGA database and GSE84437 dataset. Through independent prognostic analysis and clinical correlation analysis, 74 prognostic related genes (PRG) were screened out. A PPI network was established for PRG to identify four key genes (KG), namely LMOD1, CRYAB, VCL and MYL9. Survival analysis showed that patients with high expression of KG had poor prognosis. Multivariate Cox regression analysis showed that KG was an independent prognostic factor. TCGA database verifies the importance and significance of KG as a prognostic indicator. Functional enrichment analysis showed that KG was mainly involved in cell adhesion molecules, adhesion spots and PI3K/AKT signaling pathway. KG may be a potential therapeutic target for gastric cancer. Show less

Repetitive Transcranial Magnetic Stimulation (rTMS) is a promising intervention for Autism Spectrum Disorder (ASD), but objective markers for rTMS tolerance remain lacking. This case-control study explored gaze behavior variability toward emotional faces in ASD children undergoing rTMS, focusing on identifying subgroups associated with rTMS intolerance. Eye-tracking data (Tobii technology, preferential-looking paradigm) were collected from 104 ASD children (48 intolerant, 56 tolerant) receiving DLPFC-targeted rTMS (left high-frequency, right low-frequency). Latent Profile Analysis (LPA) identified fixation subgroups across eight conditions. Demographic (sex, age), clinical (CARS scores) differences, and profile-tolerance associations were analyzed. LPA revealed three gaze profiles: moderate non-preferential fixation (80.76%), low diverse fixation (9.62%), and increased fixation with mild variability (9.62%). Sex and CARS scores differed across profiles (age did not). Intolerance rates were 38.1%, 60.0%, and 100%, with profiles predicting rTMS intolerance (OR = 0.210, 95% CI: 0.079-0.557). ASD children exhibit heterogeneous emotional face gaze patterns. Findings highlight the need for personalized rTMS interventions, especially for those with higher CARS scores and increased emotional face fixation-at elevated intolerance risk. Show less

Stroke is a leading cause of mortality and disability globally, with post-stroke depression and post-stroke anxiety being common and significant complications that hinder recovery and adversely affect quality of life. Although these conditions frequently co-occur, their heterogeneity remains poorly understood. This study integrates the Health Ecology Model (HEM) and employs Latent Profile Analysis (LPA) to identify distinct psychological profiles of depression and anxiety among patients with acute ischemic stroke (AIS), as well as to investigate their multilevel determinants. Patients with AIS from a tertiary hospital in Guangdong Province, China, from January to November 2024 were included. Within one week of stroke onset, the data of sociodemographic, clinical characteristics, swallowing function, stroke severity, activities of daily living, resilience and social support were collected according to the HEM guidelines. The Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7 were used to assess the depression and anxiety symptoms of the patients three months after stroke onset. LPA was employed to identify distinct psychological profiles, and variables with a A total of 551 patients with AIS were included in the study, 49 were lost to follow-up or withdrew, resulting in a final analytic sample of 502 participants (91.11%). Three distinct psychological profiles were identified: no depression-anxiety (67.93%), high-risk depression-anxiety (21.12%) and major depression-anxiety (10.95%). In the multivariate analysis, the results indicated that occupation (OR = 0.61, 95% CI [0.40-0.93]), National Institutes of Health Stroke Scale (NIHSS, OR = 1.60, 95% CI [1.06-2.42]), Barthel Index (BI, OR = 1.67, 95% CI [1.27-2.19]) and hypertension (OR = 2.37, 95% CI [1.29-4.35]) were independent predictors of the high-risk depression-anxiety profile, while NIHSS (OR = 2.33, 95% CI [1.42-3.85]), BI (OR = 2.65, 95% CI [1.62-4.35]) and resilience (OR = 0.92, 95% CI [0.87-0.98]) were significantly associated with the major depression-anxiety profile. This study reveals significant heterogeneity in psychological distress among AIS survivors. Key predictors of post-stroke emotional comorbidity include occupation, hypertension, stroke severity, activities of daily living and low resilience. Early identification of high-risk individuals can significantly enhance screening and intervention strategies, particularly by focusing on symptoms such as anhedonia and nervousness. Future research should focus on longitudinal designs and objective biomarkers to better understand the mechanisms behind post-stroke emotional comorbidity. Show less

In the field of second language acquisition, there is a growing recognition of the importance of emotional factors, particularly emotional intelligence (EI), in influencing learners' willingness to communicate (WTC) in a second language (L2). However, previous studies have predominantly adopted a variable-centered approach, often overlooking individual heterogeneity and the mediating role of foreign language enjoyment (FLE) in the relationship between EI and WTC. To address these gaps, this study integrated variable-centered and person-centered approaches to examine 1111 students from Chinese private colleges, representing a distinct educational ecology. Questionnaires were used to measure EI, FLE, and L2 WTC, followed by mediation analysis and latent profile analysis (LPA). Results indicated that EI positively predicted WTC ( Show less

This study systematically examines the relationship between mindfulness and metacognition among Chinese college students through a person-centered analytical approach. Using latent profile analysis (LPA) of Five Facet Mindfulness Questionnaire (FFMQ) responses, we identified four distinct mindfulness profiles: (1) High Observation/Low Non-reactivity, (2) High Awareness/Judging, (3) Moderately Mindful, and (4) Highly Mindful. Gender differences were observed across profiles, with female students more represented in the Highly Mindful group. Hierarchical regression analyses revealed that mindfulness profiles significantly predicted metacognitive ability, with the Highly Mindful group demonstrating superior metacognitive self-regulation and learning strategy application. These findings contribute to the literature by identifying distinct mindfulness subtypes and their differential relationships with metacognition. The results suggest that educational interventions emphasizing non-judgmental present-moment awareness may be particularly effective for fostering students' metacognitive development, while highlighting the importance of considering individual differences in mindfulness training approaches. Show less

Previous studies showed that obstructive sleep apnea (OSA) is associated with dyslipidemia. However, whether micro-arousals during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep independently associated with dyslipidemia were unknown. 4472 participants with OSA-related symptoms were finally included in our cohort. Various sleep variables including micro-arousal index (MAI) were obtained from standard polysomnography (PSG) recordings. Fasting serum lipid levels were assessed at our hospital laboratory. Linear regression models were employed to investigate relationships between micro-arousals in REM and NREM sleep and lipid profile with adjusting for multiple confounding factors. Fully adjusted models demonstrated a significant dose-dependent positive correlation between the MAI during REM sleep (MAI MAI Show less

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health issue due to its high prevalence, yet the impact of accelerometer-measured physical activity on clinical outcomes remains unclear. This study aims to examine the associations of physical activity with the risk of liver cirrhosis, cancer, cardiovascular disease (CVD) incidence and mortality. 32 681 MASLD participants with accelerometer-derived physical activity data from the UK Biobank were analysed. Physical activity intensity was categorised into light (LPA), moderate (MPA) and vigorous (VPA) intensity. Cox proportional hazard and acceleration failure models were employed to assess associations between physical activity duration and outcomes. During a median follow-up of 7.5-7.9 years, 1883 deaths, 151 liver cirrhosis, 3312 cancers and 6657 CVD events were recorded. Physical activity, regardless of intensity, was consistently associated with a reduced risk of liver cirrhosis, CVD and all-cause mortality. Compared with non-MASLD individuals, our analysis indicates that longer duration of physical activity, specifically >1945 min/week of LPA or >383 min/week of MPA may theoretically eliminate the excess risk of mortality associated with MASLD. Among MASLD individuals, longer physical activity duration, regardless of intensity, was associated with reduced risks of liver cirrhosis and mortality. MPA and VPA were associated with lower CVD risk, while VPA was associated with reduced cancer risk, highlighting the potential benefits of increasing the intensity and duration of physical activity in MASLD management. Show less

Endometrial cancer (EC) is a malignant tumor arising from the endometrial epithelium and is among the most prevalent gynecological malignancies worldwide. Increasing evidence suggests that lipid profiles, hyperglycemia, and other metabolic factors play a role in EC pathogenesis. However, research on the association between lipoprotein(a) [Lp(a)] levels and EC prognosis remains limited. This retrospective cohort study analyzed Lp(a) levels in patients diagnosed with EC at Ganzhou Hospital, affiliated with Nanchang University, between January 2017 and January 2022. Lp(a) concentrations were measured post-admission, and patient prognosis was categorized as favorable or poor. Multivariate logistic regression analysis was performed to determine the adjusted odds ratio (OR) and 95% confidence interval (CI). The study included 296 EC patients, out of whom 72.3% (214/296) had a favorable prognosis, defined as no recurrence within five years post-surgery. The overall healing rate was 72.3% (214/296). When stratified by Lp(a) levels, patients in the first quantile (Q1 ≤ 122.2 g/L) had a favorable prognosis rate of 77.7% (115/148), whereas those in the second quantile (Q2 > 122.2 g/L) had a rate of 66.9% (99/148), with a statistically significant difference between groups (p < 0.05). In the multivariate regression model, the log2-transformed Lp(a) values and their corresponding ORs (95% CIs) for prognosis at two upper normal limits (ULN) were 1.7248 (1.0288 - 2.8918) and 2.0365 (1.1843 - 3.5018), respectively. Interaction analysis indicated that Lp(a) levels significantly influenced EC prognosis. Lp(a) is strongly associated with EC prognosis and holds potential clinical significance. Further studies are required to validate these findings. Show less

Amyloid deposition of human islet amyloid polypeptide (hIAPP) is closely linked to the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Developing effective inhibitors to suppress hIAPP aggregation holds significant therapeutic potential for the prevention and treatment of T2DM. Recent researches indicate that both heme and lithospermic acid (LPA) can inhibit hIAPP aggregation. However, heme is prone to induce protein damage under oxidative stress, while LPA exhibits limited inhibitory efficacy despite its antioxidant properties. To overcome these limitations, we aimed to develop a dual-component inhibitor comprising heme and LPA. thioflavin T (ThT) fluorescence, transmission electron microscopy (TEM), circular dichroism (CD) and gel electrophoresis were combined to observe the inhibitory efficacy of heme-LPA co-formulation on hIAPP aggregation. The results demonstrate that LPA and heme can synergistically inhibit hIAPP aggregation. The inhibitory effect of heme-LPA co-formulation on hIAPP aggregation is significantly stronger than that of either component alone. The heme-LPA not only prevents the complete conversion of hIAPP into β-sheet fibrillar structures but also maintains its active monomeric conformation for extended periods. Furthermore, peroxidase activity assays revealed that the presence of LPA significantly reduces the peroxidase activity of heme in a concentration-dependent manner and attenuates peptide nitration damage under H₂O₂-NO₂ Show less

The proportion of n-6 and n-3 polyunsaturated fatty acid (PUFA) in commercial pig feed is severely unbalanced. This study was conducted to investigate the effects of different n-6/n-3 PUFA ratios on growth performance and lipid metabolism of nursery pigs. A total of 240 nursery pigs (Duroc × Large White × Landrace) were fed diets with different n-6/n-3 PUFA ratios, including 10:1, 5:1, 3:1, and 1.5:1. Pigs fed diet with n-6/n-3 PUFA ratio of 1.5:1 or 3:1 had optimum average daily gain and feed to gain ratio ( 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 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 50℃, 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

Wenchang chicken, renowned for its high-quality meat, is the economic meat breed in Hainan Province, China. This study compared cage-rearing (CR) and free-range (FR) groups in terms of growth performance, slaughter performance, meat quality, IMP (inosine monophosphate) content, AAs, FAs, serum lipid metabolites, and transcriptomic and metabolomic analyses. The CR group showed increased body weight, live weight, and abdominal fat but lower leg muscle percentage and breast muscle redness, suggesting flavor differences. CR chickens had higher IMP, threonine (Thr), and pentadecanoic, oleic, and linoleic acids, while glutamate (Glu) and alpha-linolenic acid were lower compared to FR. Glycine was elevated, but histidine, myristic, and tricosanoic acids were lower in CR leg muscle. Serum analysis revealed higher total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), fatty acid synthase (FAS), thyroid-stimulating hormone (TSH), leptin (LEP), and adiponectin (ADP) in the CR group. Transcriptomic and metabolomic studies identified 252 differentially expressed genes and 34 metabolites linked to metabolic pathways. In summary, CR system can improve production performance, FR system is considered more flavorful. The results can act as a theoretical basis for selecting a suitable rearing method for this unique breed. Show less