👤 Yunjun Liang

Older adults increasingly rely on digital health resources, yet evidence regarding the relationship between eHealth literacy (eHL) and 24-hour movement behaviors (24-HMB), including physical activity (PA), sedentary behavior (SB), and sleep, remains underexplored. This study examined the associations between eHL and 24-HMB in Chinese older adults and examined self-efficacy as a potential mediator and moderator. Using a convenience sampling approach, 564 community-dwelling older adults (aged 60-74 years) were recruited from four urban Chinese cities via an online survey. A total of 553 valid cases were retained for analyses. eHL was assessed using the eHealth Literacy Scale-Web 3.0, and self-efficacy was assessed using a validated Self-Efficacy Scale. PA and SB were assessed objectively using ActiGraph GT3X+ accelerometers over three consecutive days (two weekdays and one weekend day). Sleep duration was derived from accelerometer-based estimates anchored by daily sleep logs. Multiple linear regression analyses were conducted to examine associations, and mediation and moderation were tested using PROCESS macro (Model 4 and Model 1, respectively), adjusting for age, sex, and education. After adjustment for covariates ( In this cross-sectional, urban, device-using sample of older adults, higher eHL was associated with a more favorable 24-HMB profile, particularly higher LPA and lower SB, while associations with sleep duration were weaker. Self-efficacy showed modest indirect associations consistent with partial mediation for PA and SB and also acted as a moderator of several associations. Given the observational design and modest effect sizes, findings should be interpreted cautiously and require confirmation in longitudinal or experimental studies with more representative sampling and improved sleep assessment. Show less

Negative Emotional symptoms such as depression and anxiety do not exist independently, often co-occurring in the same individual, and heterogeneity exists between individuals suffering from depression and anxiety; however, prior research has rarely investigated heterogeneity in a person-centered manner and from the perspective of college students. The main purpose of this study was to explore this heterogeneity and its association with e-Health literacy (e-HL) using Latent profile analysis (LPA), a person-centered statistical method. A total of 7,503 Chinese college students from 10 regions (including Guangdong Province, Shanghai Municipality, and Jiangsu Province) were surveyed using the Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9) to assess anxiety and depressive symptoms. LPA was employed to identify potential profiles of negative emotional symptoms and validate their robustness; binary logistic regression was used to explore differences in demographic characteristics (sex, grade ranking), sociological factors (family residential background, per capita monthly family income), and lifestyle factors (adherence to physical activity, smoking status, alcohol consumption) across profiles; analysis of variance (ANOVA) was applied to compare e-HL levels among different profiles. The two-class model was identified as the optimal classification of negative emotional symptoms: low/no negative emotional symptoms (61.49%) and high negative emotional symptoms (38.51%). Female college students, those with low per capita monthly family income, lack of regular physical exercise, and alcohol consumption habits were more likely to be categorized into the high negative emotional symptoms group (all Reliance on self-report measures may lead to recall bias and social desirability bias; the cross-sectional design cannot establish causal relationships between variables; digital addiction, a potential confounding factor that may co-occur with negative emotional symptoms and influence e-HL, was not included in the analysis. This study identified two distinct latent profiles of negative emotional symptoms among Chinese college students and their key predictive factors using LPA. The findings highlight the need for stratified early screening for high-risk groups (females, low-income families, inactive individuals, and drinkers) and the development of targeted interventions. Enhancing e-HL could be a potential pathway to improve mental health outcomes, providing actionable insights for scientific and effective mental health management in colleges and universities. Show less

To examine associations between the 24-h composition of movement behaviors (sedentary behavior [SB], light physical activity [LPA], moderate-to-vigorous physical activity [MVPA], and sleep) and physical and mental health in older adults using compositional data analysis. Data came from 4,150 adults aged ≥ 60 in the 2015 China Health and Nutrition Survey. Multiple‑balance isometric log‑ratio regression and compositional isotemporal substitution models were used to assess relative associations and the effect of time reallocation. The 24‑hour geometric mean composition was 43.1% sleep, 30.6% SB, 21.8% LPA, and 4.5% MVPA. LPA was positively associated with physical (β = 0.062, Replacing sedentary time or sleep with LPA, even in small amounts, is associated with better physical and mental health in older adults, supporting integrated 24‑hour activity guidelines that emphasize light‑intensity movement. Show less

This study examined the relationship between motor competence (MC) and Physical Activity (PA) in school-aged children, and assessed the mediating role of physical fitness, based on the Model of the Relationship between Children’s Motor Development and Obesity Risk. From March to April 2022, 1,026 children (53.6% boys, mean age 8.93 years) from four public primary schools in Shijiazhuang City, China, were recruited via stratified cluster sampling. MC was assessed using the Test of Gross Motor Development, 3rd edition (TGMD-3), PA was measured via a three-axis accelerometer, and physical fitness was evaluated according to the Chinese National Student Physical Health Standards (2014 revision). Data were analyzed using SPSS 26.0, with mediation tested via the bias-corrected bootstrap method (10,000 resamples). Ball skills ( Ball skills are critical for promoting MVPA in school-aged children, with physical fitness acting as a significant mediator. Systematic ball skill training is recommended as a core strategy to enhance physical activity via improved fitness. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined independent risk factor for atherosclerotic cardiovascular disease (ASCVD) that drives a significant residual risk through proatherogenic, proinflammatory, and prothrombotic pathways. However, current mainstay lipid-lowering therapies such as statins have limited efficacy in reducing Lp(a) levels, highlighting a critical therapeutic gap. This review aims to synthesize evidence on the role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors in targeting Lp(a). We systematically searched PubMed and Embase for clinical trials and mechanistic studies (2010-2025), using the PRISMA and AMSTAR-2 frameworks to ensure methodological rigor and demonstrated that PCSK9 inhibitors (eg, alirocumab, evolocumab, and tafolecimab) not only reduced low-density lipoprotein (LDL-C) by 55%-60% but also lowered Lp(a) by 20%-30%. The efficacy of these agents varies ethnically, with tafolecimab showing superior performance in East Asian populations, which is partly attributable to the higher prevalence of the PCSK9 R46L loss-of-function allele. Mechanistically, PCSK9 inhibitors lowered Lp(a) levels through 2 pathways: suppression of hepatic synthesis and enhanced plasma clearance. This evidence supports the 2023 ESC guidelines, which issued a Class IIa recommendation for PCSK9 inhibitor use in patients with ASCVD and elevated Lp(a) levels. Given the evolving landscape, further research is warranted to confirm the role of these therapies in precision medicine paradigms for managing Lp(a)-associated risks. Show less

Physical inactivity is a health concern for children and adolescents with neurodevelopmental disorders (NDDs) as it directly increases their risk of developing various health problems. Evidence on differences in accelerometer-assessed physical activity between children and adolescents with and without NDDs is inconclusive. And age- and body mass index (BMI)-related effects on physical activity remain unclear. The systematic literature searches were performed in 6 databases up to March 2025. Methodological quality was evaluated by the Newcastle-Ottawa Scales. Data were pooled using a random-effects model. Hedges' g was used to express the effect size index with 95 % confidence interval (CI). Meta-regression on age and BMI was also performed to investigate the potential moderating effects. Out of the 2167 studies initially identified, 28 were included in the analysis, which comprised total physical activity (TPA), moderate-to-vigorous physical activity (MVPA), and light physical activity (LPA) included in the meta-analysis, respectively. These studies involved 1060 children and adolescents with NDDs and 1820 without, aged 6.6-16.9 years. A small-to-moderate effect size exists for the difference in TPA (g=-0.299) and MVPA (g=-0.479) between children and adolescents with and without NDD, particularly indicating a difference in 12.7 min of MVPA daily. The difference in LPA was not significant (g=0.450, p = 0.125). The decline in MVPA with age was more pronounced in those with NDDs, and the difference in MVPA was smaller for those with lower BMI. The variation in MVPA differences by age and BMI highlights the need to develop better physical activity habits and reduce these disparities for children and adolescents with NDDs. Show less

Familial partial lipodystrophy type 3 (FPLD3) is a rare autosomal dominant disorder caused by mutations in peroxisome proliferator-activated receptor gamma(PPARG), which encodes the key adipogenic transcription factor peroxisome proliferator-activated receptor gamma(PPARγ). Clinical diagnosis is challenging due to phenotypic overlap with common metabolic syndromes. We identified a novel PPARG variant in a Chinese family and performed comprehensive functional characterization to elucidate its pathogenic mechanism. The proband, a 15-year-old boy presenting with atypical fat distribution, severe insulin resistance, hypertriglyceridemia, and pancreatitis, underwent clinical evaluation and whole-exome sequencing. The identified variant was confirmed by Sanger sequencing. Its functional impact was assessed through in silico modeling, luciferase reporter assays, protein stability analysis (cycloheximide chase), and evaluation of mitochondrial function (JC-1 staining) and adipocyte gene expression in cellular models. A heterozygous PPARG c.634C>T (p.Arg212Trp, R212W) variant was identified and segregated with the phenotype. Functional studies revealed that the R212W mutant exhibits a partial loss of transcriptional activity (~40% of wild-type) while retaining ligand sensitivity. Crucially, we demonstrated that the mutant protein has significantly reduced stability due to accelerated degradation. In adipocyte models, R212W expression led to impaired mitochondrial membrane potential, depleted cellular ATP levels, and downregulated expression of key metabolic genes (glucose transporter 4[GLUT4], adiponectin[ADIPOQ], fatty acid binding protein 4[FABP4], lipoprotein lipase[LPL], perilipin 1[PLIN1]). These functional deficits were partially rescued by treatment with the PPARγ agonist rosiglitazone. We report a novel pathogenic PPARG R212W variant associated with FPLD3. Our data extend beyond a simple loss-of-function model by establishing a multi-faceted pathogenic mechanism involving protein destabilization, mitochondrial dysfunction, and cellular bioenergetic failure. The partial rescue by rosiglitazone suggests a potential therapeutic avenue. This study underscores the importance of integrating clinical phenotyping with deep functional analysis to diagnose and understand rare monogenic lipodystrophies. Show less

Organic and organic-inorganic hybrid materials exhibiting room-temperature phosphorescence (RTP) and long persistent luminescence (LPL) materials have attracted growing attention for various time-resolved optoelectronic applications. To date, realizing intrinsically distinct RTP and LPL emissions within a single material system remains elusive, yet it is crucial for unlocking multifunctional applications such as multilevel optical encryption. Here, a Mn Show less

BRAF, when mutated at V600E, is a well-known potent early oncogenic driver in papillary thyroid carcinoma (PTC), with potential prognostic and therapeutic implications. Non-V600E mutations are less common and without clear functional or therapeutic significance. One class of non-V600E mutations is BRAF gene fusions, which typically involve the C-terminal kinase domain of BRAF joined to a wide repertoire of potential N-terminal fusion partners. The aim of this study was to employ a sequential algorithmic approach to identify patients with BRAF fusions based on an integrated analysis of histologic, immunohistochemistry (IHC), and molecular (NGS) features of BRAF-rearranged PTCs. Nine patients with PTC previously scrutinized as BRAF V600E negative by IHC were analyzed by NGS. The studied 9 cases showed conventional PTC growth; 2 cases displayed a minor high-grade component (tall cell and hobnailing, < 20%), 1 case qualified as high-grade differentiated thyroid carcinoma (presence of necrosis and mitotic activity > 5 MF/ 2 mm Show less

Microtubule and actin crosslinking factor 1 (MACF1) plays a critical role in cytoskeletal regulation. Pathogenic variants in We identified two Chinese patients with Our findings broaden the phenotypic spectrum of The online version contains supplementary material available at 10.1186/s40246-026-00917-y. Show less

In this study, we used optical genome mapping (OGM), conventional karyotyping, and next-generation sequencing to analyze cytogenomic alterations in 91 cases of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Whereas karyotyping detected abnormal karyotypes in 55% of cases, OGM identified cytogenetic abnormalities in 97.8% of the cases and provided clinically relevant information beyond karyotyping in ∼70% of cases. OGM detected gene rearrangements in 80% of cases, including 24 recurrent gene fusions and 21 previously unreported putative gene fusions in T-ALL. Copy number variants were detected in 93% of cases, with interstitial deletions the most common. Gene mutations were detected in 93% of cases, with NOTCH1 being most frequent (in 57% of cases). Combining all data, most T-ALL cases harbored 3 or more cytogenomic aberrations. Specific cytogenomic alterations differed among T-ALL subtypes as follows: rearrangements of BCL11B and PICALM::MLLT10, deletions of 7p, and mutations involving DNMT3A, WT1, TET2, IDH2, and FLT3 were common in early T-precursor and near-early T-precursor subtypes. Rearrangements of TLX1, KMT2A, STIL::TAL1, and NUP214::ABL1, deletions of 9p, and FBXW7 mutations were frequently associated with the cortical subtype. We conclude that integration of OGM and next-generation sequencing with karyotyping enables comprehensive cytogenomic profiling of T-ALL that improves detection of clinically relevant genomic alterations and may inform disease classification and future studies of risk stratification. Show less

Liver X receptors (LXRs), transcription factors belonging to the nuclear receptor superfamily, exist as two isoforms, LXRα (NR1H3) and LXRβ (NR1H2), that orchestrate cholesterol absorption, transport and excretion. Beyond their canonical roles in lipid homeostasis, LXRs modulate glucose metabolism, inflammatory responses and cellular proliferation. Emerging evidence implicates dysregulated LXRs activity in the pathogenesis of chronic liver diseases (CLDs), including viral hepatitis, metabolic dysfunction‑associated steatotic liver disease and hepatocellular carcinoma. However, the therapeutic potential of LXRs modulation remains paradoxical: While activation mitigates hepatic injury by maintaining cholesterol homeostasis and suppressing inflammation, concurrent upregulation of sterol regulatory element‑binding protein 1c exacerbates lipogenesis, potentially aggravating hepatosteatosis. The present review synthesized current insights into the dual regulatory mechanisms of LXRs in CLDs, critically evaluates their context‑dependent roles and highlights the imperative to balance therapeutic efficacy with metabolic side effects in future drug development. Show less

The role of efferocytosis in chronic rhinosinusitis (CRS), particularly CRS with nasal polyps (CRSwNP), remains poorly understood. We comprehensively characterized efferocytosis in CRS and determined its association with inflammatory endotypes and clinical outcomes in CRSwNP. Efferocytosis-related marker expression between nasal polyps and healthy nasal mucosa was detected by quantitative real-time PCR and immunohistochemistry. Public single-cell RNA sequencing profiles of CRS were reanalyzed to dissect efferocytosis at single-cell resolution. Associations between efferocytosis and tissue inflammation were evaluated by Spearman correlation. Regression models and receiver operating characteristic analyses assessed the predictive capability of efferocytosis for CRSwNP recurrence. Compared with controls, CRSwNP exhibited widespread efferocytosis deficiency, including "find me" signals (CX3CR1, S1PRs, P2RY2, GPR132), "eat me" signals (ITGAV, MerTK, Tim1, ADGRB1), "don't eat me" signal CD300a, postengulfment signals (ABCA1, NR1H3/2, PPARδ/γ), and bridging molecule MFGE8. Macrophages, the principal efferocytic cells, shifted from homeostatic C3 Insufficient phagocytosis and increased antiphagocytosis activity are hallmarks of efferocytosis deficiency in CRS and are associated with the severity of inflammation and the clinical outcome of CRSwNP. Show less

The development and function of B lymphocytes require the precise integration of signaling, transcriptional networks, and metabolic programs. While interferon (IFN)-inducible proteins can bridge innate and adaptive immunity, their roles in B cells remain poorly defined. Here, we identified RNF213, a giant IFN-inducible RING finger E3 ligase, as a key orchestrator of B-cell biology. Mice lacking Rnf213 exhibited defective splenic B-cell development, impaired B-cell receptor (BCR) signaling, and compromised metabolic activity. Mechanistically, RNF213 targeted the transcription factor SPIB for proteasomal degradation via K11-linked ubiquitylation. In Rnf213‑deficient B cells, stabilized SPIB transcriptionally upregulated Pik3c3, thereby increasing phosphatidylinositol 3-phosphate (PI3P) production. Excess PI3P recruited PTEN to early endosomes, where PTEN hydrolyzed phosphatidylinositol-3,4,5-trisphosphate (PIP3) and attenuated AKT-mTOR signaling. Strikingly, both genetic deletion of Spib and pharmacological inhibition of PIK3C3 restored AKT-mTOR activation, metabolic fitness, and B-cell development in Rnf213-null mice. Furthermore, Rnf213 deficiency impaired both T-independent and T-dependent antibody responses, highlighting its critical role in humoral immunity. Overall, our work reveals a novel ubiquitin-dependent circuit that links interferon signaling to the transcriptional and metabolic control of B-cell homeostasis. This study also establishes RNF213 as a crucial bridge between innate immune sensing and the dynamic regulation of lymphocyte development. Show less

The stimulator of interferon genes (STING) is a central mediator of innate immune sensing and represents a critical regulator of chronic inflammation. Upon persistent infection, excessive neutrophil activation leads to the formation of neutrophil extracellular traps (NETs) that damage the tissues. However, the mechanism by which STING signaling regulates NETs formation under chronic inflammatory conditions remains poorly understood. In this study, using LPS-induced murine endometritis models in wild-type and STING-deficient mice, we demonstrated that STING deficiency significantly suppressed myeloperoxidase activity, and diminished NETs formation. We identified neutrophil surface molecular CD11b as a key downstream target of STING, whose expression was transcriptionally regulated via IRF7. Furthermore, the STING-IRF7 axis was found to drive lipocalin-2 (LCN2) expression, which acted through its receptor MC4R to upregulate intracellular adhesion molecule-1 (ICAM-1), thereby facilitating neutrophil recruitment and NETosis during LPS stimulation. The role of this pathway was validated both Our findings revealed a novel mechanism in which the STING-IRF7 pathway exacerbated endometrial inflammation and tissue damage by coordinately upregulating CD11b and activating the LCN2-ICAM-1 axis. Consequently, targeting the STING signaling pathway may offer a promising therapeutic strategy for chronic endometritis. Show less

Sepsis, characterized as a systemic inflammatory response triggered by pathogen invasion, represents a continuum that may progress from mild systemic infection to severe sepsis, potentially culminating in septic shock and multiple organ dysfunction syndrome. A pivotal element in the pathogenesis and progression of sepsis involves the significant disruption of oncological metabolic networks, where cells within the pathological milieu exhibit metabolic functions that diverge from their healthy counterparts. Among these, purine metabolism plays a crucial role in nucleic acid synthesis. However, the contribution of Purine Metabolism Genes (PMGs) to the defense mechanisms against sepsis remains inadequately explored. Leveraging bioinformatics, this study aimed to identify and substantiate potential PMGs implicated in sepsis. The approach encompassed a differential expression analysis across a pool of 75 candidate PMGs. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were employed to assess the biological significance and pathways associated with these genes. Additionally, Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) methodologies were implemented to identify key hub genes and evaluate the diagnostic potential of nine selected PMGs in sepsis identification. The study also examined the correlation between these hub PMGs and related genes, with validation conducted through expression level analysis using the GSE13904 and GSE65682 datasets. The study identified twelve PMGs correlated with sepsis, namely AK9, ENTPD3, NUDT16, GMPR2, PKM, RRM2B, POLR2J, POLE3, ADCY3, ADCY4, ADSSL1, and AMPD1. Functional analysis revealed their involvement in critical processes such as purine nucleotide and ribose phosphate metabolism. The diagnostic capability of these PMGs to effectively differentiate sepsis cases underscored their potential as biomarkers. This research elucidates twelve PMGs associated with sepsis, providing valuable insights into novel biomarkers for this condition and facilitating the monitoring of its progression. These findings highlight the significance of purine metabolism in sepsis pathogenesis and open avenues for further investigation into therapeutic targets. Show less

Exploding head syndrome (EHS) is a parasomnia characterized by the perception of loud noises originating from inside the head during sleep transitions, often accompanied by visual phenomena and fear. Treatment remains challenging due to unknown etiology and limited therapeutic options. We report a 75-year-old man with chronic exploding head syndrome experiencing lightning-like sensations, thunder-like sounds, sleep paralysis, and intense fear during sleep onset. Episodes occurred multiple times weekly for over five years. Initial treatments, including gabapentin, valproic acid, amitriptyline, and buspirone, proved ineffective. The patient was subsequently treated with sublingual ketamine, starting at 25 mg every third night and escalating to nightly dosing. After one month, episode frequency decreased from 3-4 times weekly to once every two weeks. By three months, episodes occurred monthly with reduced intensity. After six months, the patient experienced only occasional sleep paralysis with the complete resolution of exploding head syndrome and reported improved quality of life. Ketamine's mechanism likely involves N-methyl-D-aspartate (NMDA) receptor modulation, brain-derived neurotrophic factor release, and σ1 receptor agonism, promoting neuroplasticity and sleep regulation. This case represents a reported successful treatment of exploding head syndrome with ketamine, suggesting a potential therapeutic approach for this refractory parasomnia. Further studies are warranted to evaluate ketamine's efficacy in exploding head syndrome treatment. Show less

Cognitive impairment is acknowledged as an early stage between normal aging and Alzheimer's disease, emphasizing the need for prompt intervention. There is growing evidence that the gut-brain axis plays a role in regulating cognitive function, indicating that probiotics and their derivatives may impact cognitive functions through the brain-gut axis. In this study, we isolated and identified a novel bacterial strain Show less

Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompletely defined. Here, we found that BAF60a functions as a chromatin regulator that sustains biphasic GSIS and preserves β cell function under metabolic stress conditions. BAF60a was downregulated in β cells from obese and diabetic mice, monkeys, and humans. β cell-specific inactivation of BAF60a in adult mice impaired GSIS, leading to hyperglycemia and glucose intolerance. Conversely, restoring BAF60a expression improved β cell function and systemic glucose homeostasis. Mechanistically, BAF60a physically interacted with Nkx6.1 to selectively modulate chromatin accessibility and transcriptional activity of target genes critical for GSIS coupling in islet β cells. A BAF60a V278M mutation associated with decreased β cell GSIS function was identified in human donors. Mice carrying this mutation, which disrupted the interaction between BAF60a and Nkx6.1, displayed β cell dysfunction and impaired glucose homeostasis. In addition, GLP-1R and GIPR expression was significantly reduced in BAF60a-deficient islets, attenuating the insulinotropic effect of GLP-1R agonists. Together, these findings support a role for BAF60a as a component of the epigenetic machinery that shapes the chromatin landscape in β cells critical for glucose sensing and insulin secretion. Show less

This patent application pertains to a novel class of peptide triagonists, generally represented by Formula I. These peptides exhibit selective activities toward GIPR (gastric inhibitory polypeptide receptor), GLP-1R (glucagon-like peptide-1 receptor), and GCGR (glucagon receptor). The unique pharma-cological profile of these triagonists offers promising therapeutic potential for the management of various conditions, including type 2 diabetes mellitus (T2DM), weight management, nonalcoholic fatty liver disease, etc. Show less

Obesity and weight regulation disorders are determined by the combined effects of genetics and environment. Polygenic obesity results from the combination of common variants in several genes which predisposes the individual to obesity and its related complications. In contrast, monogenic obesity results from changes in single genes, especially those in leptin-melanocortin pathway, and presents with early onset severe obesity, with or without other syndromic features. Rare variants in melanocortin 4 receptor are the commonest form of monogenic obesity. In addition, structural variation in small or large segments of chromosomes may also present with syndromic forms of obesity. Prader-Willi Syndrome, caused by imprinting errors in chromosome 15q11-13, is the most prevalent genetic cause of severe hyperphagia and obesity. With the advances in technologies, the past decade has witnessed a revolution in the identification of novel genetic causes of obesity, primarily in genes related to the leptin melanocortin pathway. The availability of safe melanocortin analogs holds the potential for targeted therapies for some of these disorders. This review summarizes known and novel rare genetic forms of obesity, along with approaches for the clinical investigation of copy number and sequence variants. The goal is to provide a reference for practicing clinicians to encourage genetic testing in obesity. IMPACT: What does this article add to the existing literature? Genetic obesity is an expanding frontier with potential to change management. Here, we summarize current information on the genetic causes of obesity and provide guidance for genetic testing. Emerging treatments may provide targeted precise treatment and change management practices. 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

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

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

Atrial fibrosis serves as a key pathological basis for atrial fibrillation, significantly elevating the risk of cardiovascular events. However, its molecular mechanisms remain incompletely understood. N⁶-methyladenosine (m6A) modifications have been proven to involve in the pathological processes of cardiovascular diseases, yet its role in atrial fibrosis remains unclear. m6A plays an important role in disease pathogenesis via mRNA modification. This study aimed to define the role of m6A modifications in the fibrotic atria of rats with chronic intermittent hypoxia (CIH). A CIH model was established using rats living in an intermittent hypoxia simulation chamber filled with oxygen and nitrogen. Myocardial function and atrial fibrosis were examined by echocardiography, electrophysiology, and histopathology. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and mRNA sequencing (mRNA-Seq) were performed on atria from control and CIH rats to identify differential m6A methylated genes and transcripts and further analyze their coexistence. Functional enrichment of the conjoint genes was analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes assays. m6A distribution of the conjoint gene ANGPTL4 (angiopoietin like 4) was also observed. ANGPTL4 and m6A-related gene expression levels were determined by quantitative real-time polymerase chain reaction. CIH led to electrical conduction dysfunction and abnormal expression of fibrosis-associated proteins, indicating successful atrial fibrosis. Conjoint analysis identified 10 genes with upregulated m6A peaks and transcripts and 24 genes with downregulated m6A peaks and transcripts. These genes were functionally enriched in the calcium ion transport-related and fibrosis pathways (extracellular matrix receptor interaction). The m6A modification level of ANGPTL4 mRNA and the expression of four m6A regulatory enzymes were significantly different between control and CIH rats. Our results revealed that m6A modification plays a crucial role in atrial fibrosis and may provide new therapeutic strategies for this disease. Show less

Tea polyphenols are a class of natural plant compounds with potent antioxidant properties, and their critical role in regulating lipid metabolism has been demonstrated in numerous studies. However, systematic research on the effects of tea polyphenols on lipid metabolism in lion-head geese remains limited. In this study, we examined the impact of tea polyphenols on lipid metabolism in geese through an integrative analysis of transcriptomics and metabolomics. A total of 240 healthy male lion-head geese with similar body weights at 1 day of age were randomly allocated into two treatment groups (6 replicates per group, with 20 geese per replicate). The control group received a basal diet, while the experimental group was supplemented with 1000 mg/kg of tea polyphenols (50.4 % catechin purity) in the basal diet for 18 weeks. The results indicated that serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) activities were significantly increased (P < 0.05), while malondialdehyde (MDA) levels were significantly decreased (P < 0.05) in the tea polyphenol group compared to the control group. Additionally, serum triglycerides (TG), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities were significantly lower (P < 0.05) in the tea polyphenol group than in the control group. Hepatic transcriptomic analysis further revealed that tea polyphenols significantly modulated the expression of several genes involved in lipid metabolism, including angiopoietin-like 4 (ANGPTL4), which plays a role in regulating lipid homeostasis, as well as glycerophosphodiester phosphodiesterase domain containing 2 (GDPD2), immunoglobulin heavy chain (IGH), proto-oncogene protein c-fos (FOS), and matrix metallopeptidase 1 (MMP1), etc. Serum metabolomic analysis also demonstrated significant alterations in lipid metabolites induced by tea polyphenols, including the downregulation of fatty acyl metabolites such as L-Palmitoylcarnitine and Hexadecanal. Moreover, the combined analysis revealed a strong positive correlation between ANGPTL4 and the organic compounds of steroidal saponins, such as Glucoconvallasaponin B, and negative correlations with glycerophospholipid metabolites, such as LysoPC (P-16:0). The comprehensive analysis suggests that the inclusion of tea polyphenols in the diet enhances the antioxidant capacity of lion-head geese, improves hepatic lipid profiles, and regulates lipid metabolism via modulating lipid metabolism-related genes and metabolites. Show less

Angiopoietin-like 4 (ANGPTL4) belongs to the family of angiopoietin- like proteins. The involvement of ANGPTL4 in various aspects of lipid metabolism and inflammation has become an important area of research. A thorough search on PubMed related to ANGPTL4, lipid metabolism, and inflammation was performed. Over the past two decades, the recognition of ANGPTL4 as a potent regulator of lipid metabolism has substantially increased. As part of the senescence-associated secretory phenotype, ANGPTL4 also serves as an inflammatory mediator. Considering the advancements in ANGPTL4 research, we have highlighted that ANGPTL4 acts as a key node linking lipid metabolism and inflammation. ANGPTL4 impacts inflammation by regulating lipid metabolism. It affects critical enzymes (lipoprotein lipase, hepatic lipase, endothelial lipase, and acetyl-CoA carboxylase), regulatory factors (AMPK, cAMP, SLC7A11, GPX4, and mTOR), and receptors (LepR, CD36, and PPARγ) of lipid oxidation, synthesis, and peroxidation, thereby affecting immune cells and inflammatory pathways. Understanding the potential association and the therapeutic value of ANGPTL4 for regulating lipid metabolism and inflammation could contribute to drug discovery and therapeutic development. Show less