To explore the therapeutic mechanism of The active components and disease targets of JZQBR were screened using TCMSP and GeneCards databases, followed by protein-protein interaction analysis and GO an Show more
To explore the therapeutic mechanism of The active components and disease targets of JZQBR were screened using TCMSP and GeneCards databases, followed by protein-protein interaction analysis and GO and KEGG enrichment analyses. In the animal experiments, Network pharmacology identified 65 potential targets, with quercetin, kaempferol, and luteolin as the core components and IL-6, IL-1β, and TNF‑α as the key targets. The targets were enriched mainly in the pathways involving inflammatory responses and diabetic complications. In the JZQBR improves T2DM complicated with hyperlipidemia possibly by multi-target regulation of the inflammation-metabolism network. Show less
Aortic dissection is a life-threatening cardiovascular disease whose complex cellular pathophysiology is studied using various mouse models. To systematically evaluate their fidelity, we performed cro Show more
Aortic dissection is a life-threatening cardiovascular disease whose complex cellular pathophysiology is studied using various mouse models. To systematically evaluate their fidelity, we performed cross-species single-cell RNA sequencing, integrating data from human aortic dissection with five mouse models (BAPN, Ang-II, Ang-II apoE Show less
Hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) are characterized by left ventricular hypertrophy and diastolic dysfunction. Despite overlapping remodeling features, their disti Show more
Hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) are characterized by left ventricular hypertrophy and diastolic dysfunction. Despite overlapping remodeling features, their distinct mechanisms and therapeutic responses remain unclear. This study integrated genetic, imaging, and proteomic data to identify key mediators underlying β1-adrenergic receptor blockers (β1-blockers)-related therapeutic heterogeneity between HHD and HCM. Genetic instruments for β1-blockers were derived from two genome-wide association studies and integrated with cardiac magnetic resonance radiomic traits and plasma proteomic data from the UK Biobank, along with disease outcomes from FinnGen. A refined two-stage network Mendelian randomization framework with pleiotropy-robust estimators identified mediators of treatment response. To further elucidate their biological and clinical significance, additional analyses were performed, including drug-target profiling, molecular docking, adverse events (AEs) assessment, and drug prediction. We identified three types of imaging features and ten mediator proteins that contributed to therapeutic responses in HHD and HCM. These mediators were categorized as either mediating (aligned with therapeutic outcomes) or suppressing (opposing therapeutic outcomes). Left ventricular regional radial strain acted as a suppressing factor in HHD but a mediating factor in HCM, whereas end-diastolic and end-systolic volumes consistently showed suppressing effects in both. Regional myocardial wall thickness also exerted a suppressing role in HCM. Among protein mediators, APOE, CGREF1, ITGA5, LSP1, NOS3, and NPPB were linked to HHD, whereas DUSP13, ITGA11, NID1, and SERPINA4 were related to HCM. Specifically, APOE, ITGA5, NOS3, NPPB, DUSP13, and ITGA11 acted as mediating factors, while CGREF1, LSP1, NID1, and SERPINA4 served as suppressing ones. These findings remained robust after pleiotropy adjustment and other genetic analyses. Molecular docking revealed interactions between ADRB1, the β1-blockers target, and downstream proteins, while drug prediction identified eight potential compounds linked to these mediators. Additionally, AE analyses indicated that some targets, such as DUSP13, could both mitigate and aggravate common AEs while contributing to cardiac therapy. This integrative multi-omics analysis revealed distinct imaging and proteomic mechanisms of genetically proxied β1-blockers in HHD and HCM, providing genetic evidence for differential therapeutic responses and highlighting molecular targets for precision cardiovascular therapy. Show less
Hypertrophic scar (HS) represents a skin fibroproliferative disease characterized by a high incidence, frequent recurrence, and limited treatment options. Thus, identifying new targets to optimize the Show more
Hypertrophic scar (HS) represents a skin fibroproliferative disease characterized by a high incidence, frequent recurrence, and limited treatment options. Thus, identifying new targets to optimize the treatment of HS is of critical importance. Using summary statistics from the eQTLGen Consortium, Decode database, and FinnGen cohort, we conducted transcriptome-wide and proteome-wide Mendelian randomization (MR) to discover potential pharmacological targets against HS, with subsequent validation via RNA sequencing. Upstream regulators and downstream mechanisms were further investigated to better understand the roles of the pathogenic gene. Drug prediction, molecular docking, and molecular dynamics (MD) simulation were employed to estimate the value of potential drugs for HS. A high level of fibroblast growth factor receptor 1 (FGFR1) significantly increased the risk of HS according to transcriptome-wide (P = 0.011) and proteome-wide MR (P = 0.002) analyses. RNA-seq further validated the high expression of FGFR1 in HS. Gene-gene interaction network and enrichment analysis identified FGFR1 as the core gene driving the progression of HS, highlighting multiple biosynthetic processes. Pharmacological evaluation of candidate drugs predicted stable binding between Ro-4396686 and FGFR1. Our findings suggest that FGFR1 can serve as promising target for optimizing HS treatments, potentially reducing the costs of drug development. Show less
Colorectal cancer (CRC) remains a major global health challenge, underscoring the need for reliable biomarkers to improve prognosis and therapeutic stratification. In this study, we comprehensively in Show more
Colorectal cancer (CRC) remains a major global health challenge, underscoring the need for reliable biomarkers to improve prognosis and therapeutic stratification. In this study, we comprehensively investigated the expression pattern, clinical significance, molecular functions, and immunological implications of LINGO1 in CRC. Integrative analyses of TCGA and GEO datasets, together with validation in 72 clinical CRC samples, demonstrated that LINGO1 is markedly overexpressed in tumors and strongly associated with advanced clinicopathological features and poor patient outcomes. Functional experiments revealed that both knockdown of LINGO1 in SW480 and LoVo cells and overexpression of LINGO1 in HCT116 cells significantly modulate malignant phenotypes, including proliferation, migration, invasion, and angiogenic capacity. Transcriptome-wide and pathway enrichment analyses further indicated that high LINGO1 expression is linked to epithelial-mesenchymal transition, angiogenesis, Wnt/β-catenin signaling, and other oncogenic pathways. Immunogenomic profiling, supported by multiplex immunofluorescence staining, showed that elevated LINGO1 is associated with an immunosuppressive tumor microenvironment characterized by reduced CD8⁺ T-cell infiltration and diminished GZMB expression, alongside upregulation of multiple immune checkpoint molecules. Collectively, our findings identify LINGO1 as a novel oncogenic driver and immune-modulatory biomarker in colorectal cancer, with potential value for prognosis and therapeutic targeting. Show less
Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. Howev Show more
Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. However, adaptive changes in respiratory metabolism and molecular mechanisms in lung tissues of small mammals under extreme water shortage conditions remain unclear. This study hypothesized that small desert mammals can adapt to extreme water shortage environments by regulating the plasticity of lung tissue gene expression and respiratory metabolism. Using 29 wild-caught Siberian jerboas ( 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 physic Show more
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
Physical activity (PA) is known to enhance brain health; however, prior research has predominantly concentrated on the total volume of PA, often overlooking the frequency of daily PA on an hourly basi Show more
Physical activity (PA) is known to enhance brain health; however, prior research has predominantly concentrated on the total volume of PA, often overlooking the frequency of daily PA on an hourly basis. This prospective cohort study examined 69,393 middle-aged and older adults, utilizing wrist-worn accelerometer data to assess PA. A novel PA frequency score was developed, which integrated light PA (LPA) and moderate-to-vigorous PA (MVPA) across 18 hourly segments (6:00 AM-12:00 AM). Participants were categorized into Inactive, Active, and Very Active groups. After adjusting for potential confounders, it was observed that individuals in the Active and Very Active groups exhibited a reduced risk of developing brain disorders such as dementia, anxiety, depression, migraine, Parkinson's disease, and stroke over a median follow-up period of 7.41 years. Magnetic Resonance Imaging (MRI) findings demonstrated that each unit increase in the PA frequency score correlated with a 51.55 mm Show less
The neurovascular unit (NVU) represents a multicellular functional ensemble pivotal to the preservation of cerebral homeostasis, encompassing endothelial cells, pericytes, glial cells (astrocytes, mic Show more
The neurovascular unit (NVU) represents a multicellular functional ensemble pivotal to the preservation of cerebral homeostasis, encompassing endothelial cells, pericytes, glial cells (astrocytes, microglia, oligodendrocytes), and neurons. This complex orchestrates the regulation of blood-brain barrier (BBB) integrity, cerebral blood flow (CBF), and the metabolic microenvironment requisite for neuronal viability and functional competence. Accumulating lines of evidence have underscored that NVU dysfunction constitutes a critical early pathological event in neurodegenerative disorders, including Alzheimer's disease (AD) and vascular dementia (VaD). The present review summarizes the structural composition and core physiological functionalities of the NVU, with particular emphasis on the emerging role of lipid metabolism dysregulation in mediating NVU impairment-an aberrant process encompassing lipid droplets, apolipoprotein E (APOE), ATPase phospholipid transporting 11B (ATP11B), triggering receptor expressed on myeloid cells 2 (TREM2), and ATP-binding cassette (ABC) transporters. We further delineate the mechanisms by which disrupted lipid homeostasis elicits neuroinflammation, amplifies oxidative stress, impairs amyloid-β (Aβ) clearance, and precipitates BBB breakdown, ultimately culminating in cognitive decline. Simultaneously, this review examines controversies within the field, such as the specific role of apolipoprotein E ε4 allele (APOE4) in disease and highlights the significant pathophysiological differences between preclinical animal models and human diseases. Therapeutic strategies targeting lipid metabolism or the blood-brain barrier still face considerable challenges in clinical translation. Meanwhile, emerging tools such as lipidomics contribute to systematically analyzing the associated dysregulated lipid networks, thereby aiding in the identification of novel therapeutic targets. Show less
Alzheimer' s disease (AD) is a progressive neurodegenerative disorder characterized by a spectrum of cognitive impairments, ranging from mild memory loss to severe cognitive decline and, ultimately, d Show more
Alzheimer' s disease (AD) is a progressive neurodegenerative disorder characterized by a spectrum of cognitive impairments, ranging from mild memory loss to severe cognitive decline and, ultimately, death. The global incidence of AD is projected to increase significantly, with late-onset AD being predominantly sporadic in nature. Over the past three decades, the Apolipoprotein E (APOE) gene has been recognized as the most important single genetic determinant of sporadic AD risk. The APOE4 allele is a major risk factor for AD and is known to exacerbate the pathological process for AD. Identifying protective variants that may reduce the risk or delay the onset of AD is of great significance for the development of effective treatments. This review comprehensively examines the protective effects of APOE and its related protective mutations. It also explores the impact of these unique protective variants at the cellular level during the pathological progression of AD. Furthermore, the review compiles new insights for AD treatment offered by these protective mutations, exploring the potential applications of APOE and its related protective variants in advanced therapeutic strategies, including gene editing, RNA editing, and stem cell therapy. Show less
This study examined the associations between 24-hour movement behaviors and health-related fitness in university students, and estimated the substitution effects using a compositional isotemporal subs Show more
This study examined the associations between 24-hour movement behaviors and health-related fitness in university students, and estimated the substitution effects using a compositional isotemporal substitution model. This study was conducted between May and June 2023, using a combination of convenience and random sampling to recruit 325 undergraduate students from Tianjin University of Science & Technology as participants, including 167 males and 158 females. Daily 24-hour activity behaviors were measured using a triaxial accelerometer(ActiGraph GT3X+), including moderate-intensity physical activity(MPA), vigorous-intensity physical activity(VPA), light-intensity physical activity(LPA), sedentary behaviors(SB), and sleep(SLP) duration. Body composition was assessed via body mass index(BMI), waist circumference, and body fat percentage. Muscular strength was measured by handgrip strength, cardiorespiratory fitness was measured by vital capacity and maximum oxygen uptake(VO₍₂ max)), and flexibility was assessed by the sit-and-reach test. Compositional data analysis was used to investigate the associations between activity behaviors and health-related physical fitness. A 15-minute isotemporal substitution model was applied to predict the effects of replacing one activity with another on outcome variables. The mean age of male participants was(19.74±1.16) years, and that of female participants was(19.51±1.29) years. Based on 24-hour compositional activity behavior analysis, college students spent an average of 16.42 minutes(1.14% of the day) in MPA, 26.57 minutes(1.85%) in VPA, 150.92 minutes(10.48%) in LPA, 645.78 minutes(46.05%) in SB, and 561.31 minutes(40.21%) in SLP. After adjusting for covariates including sex and age, isotemporal substitution models revealed that replacing an equivalent amount of sedentary time with MPA was associated with a reduction in BMI by 0.07-0.19 units, body fat percentage by 0.53-0.59 units, waist circumference by 0.16-0.27 cm, an increase in vital capacity by 119.18-152.67 mL, VO₍₂ max) by 1.76-1.88 mL/(kg·min), handgrip strength by 0.86-1.46 kg, and sit-and-reach performance by 0.19-0.38 cm. Similarly, increasing VPA led to decreases in BMI by 0.14-0.16 units, body fat percentage by 0.49-0.54 units, waist circumference by 0.12-0.23 cm, increases in vital capacity by 127.45-160.84 mL, VO₍₂ max) by 1.91-2.03 mL/(kg·min), handgrip strength by 0.98-1.56 kg, and sit-and-reach by 0.14-0.32 cm. Increasing LPA result ed in BMI increases of 0.11-0.12 units, handgrip strength increases of 0.65 kg, and sit-and-reach increases of 0.21 cm. Increasing SLP was associated with BMI reduction of 0.04 units and waist circumference reduction of 0.09 cm. MPA had the most significant effect on improving BMI, body fat percentage, and waist circumference, while VPA was more effective in enhancing cardiorespiratory fitness, muscular strength, and flexibility. SLP had a modest positive effect on BMI and waist circumference but was less impactful than MPA and VPA. SB and LPA were generally unfavorable for health-related physical fitness. Show less
no PDFDOI: 10.19813/j.cnki.weishengyanjiu.2026.01.011
Indigenous chickens in tropical regions routinely survive high environmental temperatures (40-45 °C) that cause significant mortality and production loss in commercial breeds, yet the genetic mechanis Show more
Indigenous chickens in tropical regions routinely survive high environmental temperatures (40-45 °C) that cause significant mortality and production loss in commercial breeds, yet the genetic mechanisms of thermotolerance remain poorly understood. This study integrated genome-wide selective scans across 14 geographically and climatically diverse chicken breeds with multi-tissue expression data, gene expression quantitative trait locus (eQTL) analysis, transcriptome-wide association study (TWAS), and cross-species phenome-wide association study (PheWAS) to validate candidate genes. We identified 25 high-confidence genes under selection, with ATP1A1, PLCB4, RYR2 and AKT3 forming a regulatory hub coordinating cardiovascular, calcium and survival signaling. These genes converge on interconnected adrenergic, calcium, and GnRH signaling pathways, with coordinated expression across heart, hypothalamus, and liver forming an integrated thermoregulatory axis. The eQTL integration analysis using ChickenGTEx data identified 359 tissue-specific cis-eQTLs in selected regions. Additionally, TWAS analysis linked ATP1A1 to 145 gene-trait associations across 13 tissues and 14 trait categories (hepatic regulation, β = -2.13, p = 4.21 × 10⁻¹²), and cross-species PheWAS validated conserved roles in cardiovascular function (RYR2, resting heart rate p = 4.9 × 10⁻¹²), and ionic homeostasis (ATP1A1, chloride p = 1.18 × 10⁻³). In parallel, we also identified robust genomic signatures of domestication in classic candidate genes (TSHR, TBC1D1, BDNF), highlighting how initial separation from Red Jungle Fowl and subsequent adaptation to diverse climates have shaped the genetic and physiological diversity of the domesticated chicken. Collectively, our results reveal an integrated cardio-neuroendocrine calcium network driving heat adaptation, providing potential targets for breeding heat-tolerant chickens. Show less
Aging worsens Alzheimer's disease (AD) peripheral metabolism and central pathology, yet few interventions are effective when started late. Methionine restriction (MR) induces the hepatokine FGF21 and Show more
Aging worsens Alzheimer's disease (AD) peripheral metabolism and central pathology, yet few interventions are effective when started late. Methionine restriction (MR) induces the hepatokine FGF21 and may protect brain function, but its efficacy and mechanisms when started late are unclear. Fourteen-month-old male APP/PS1 mice received 17 weeks of MR (0.17% methionine); behavioral, histological, and molecular assays were performed and hippocampal FGFR1 was knocked down by adeno-associated virus. Late-life MR improved peripheral glucose/lipid profiles, reduced Aβ deposition, preserved synaptic markers, and suppressed neuroinflammation. MR-induced hepatic FGF21 and brain FGFR1-AMPKα signaling to inhibit NFκB; hippocampal FGFR1 knockdown abolished MR's neuroprotective effects while leaving peripheral metabolic changes intact. Even when initiated in late life, MR robustly reduces AD pathology via the hepatic FGF21-brain FGFR1 axis, independent of peripheral metabolic changes. These preclinical findings position MR and FGF21-FGFR1 axis as actionable late-life intervention targets with potential for clinical translation. Show less
Hongbin Zhang, Li Qiao, Fan Yang+5 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
Elucidating effective components and mechanisms of traditional Chinese medicine (TCM) formulas remains a critical challenge for modernization. ErShiWei RouDouKou Pills (ESWRDK), a Tibetan formula with Show more
Elucidating effective components and mechanisms of traditional Chinese medicine (TCM) formulas remains a critical challenge for modernization. ErShiWei RouDouKou Pills (ESWRDK), a Tibetan formula with cardiovascular potential, lacks systematic exploration of its anti-atherosclerotic (AS) material basis and mechanisms. A novel six-stage cascade focused strategy integrating three-dimensional filtering mode, qualitative characterization, multi-component quantification, anti-AS efficacy, multi-lipidomics and bioactive compounds evaluation was proposed, advancing TCM research by holistic and multi-layered approach. UHPLC-MS combined with mass defect-ion intensity filtering (MD-ITF), DPIs, Nl and FBMN employed for profiling. Nine characteristic components were quantitated. A 12-week high-fat diet was fed to ApoE Firstly, the MD-ITF method and structural classification was established for complicated matrix. Secondly, 426 chemical components including 74 low-abundance were characterized. Thirdly, 9 characteristic components were quantified, and content distribution were profiled. Fourthly, ESWRDK reduced lipids, inflammation, and aortic plaques in AS mice. Fifthly, a total of 38, 23 and 48 differential biomarkers were identified predominantly linked to glycerophospholipids (GP) metabolism. WB confirmed ESWRDK downregulated hepatic PLA2, upregulated p-AMPK/AMPK and PPAR-α, and suppressed SREBP-1, orchestrating and mitigating lipid dysregulation. Finally, dehydrodiisoeugenol and agarotetrol bound PLA2, formed stable 1:1 static quenchingand inhibited PLA2 activity in vitro. A novel six-stage cascade-focused strategy was successfully established to elucidate ESWRDK's anti-AS mechanisms, offering feasible paradigm for advancing modernization of TCM. Show less
Atherosclerosis (AS) is a prevalent typical chronic inflammation disease characterised by lipid deposition, immune cell infiltration and inflammatory response in the arterial intima. The long-term tre Show more
Atherosclerosis (AS) is a prevalent typical chronic inflammation disease characterised by lipid deposition, immune cell infiltration and inflammatory response in the arterial intima. The long-term treatments of the existing drugs suffered safety concerns. Show less
Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible Show more
Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible mechanism by which TUG1 inhibits neural repair subsequent to ICH through adjusting miR-381-3p/brain-derived neurotrophic factor (BDNF). After the ICH model was created, miR-381-3p agomir and pcDNA-TUG1 were injected. The neural function of rats was estimated using the modified neurological severity score. To quantify the expression of genes and proteins, western blotting, immunohistochemistry, and qRT-PCR were used. To confirm the interaction between TUG1 and miR-381-3p and between miR-381-3p and BDNF mRNA, a luciferase reporter assay was employed. In rats treated with miR-381-3p agomir, a trend of improvement in neurological dysfunction was observed, while the pcDNA-TUG1-treated ones showed deterioration. Furthermore, miR-381-3p agomir increased, while pcDNA-TUG1 reduced the expression level of BDNF in ICH rats. TUG1 and BDNF mRNA were validated to attach directly to miR-381-3p. Overexpressing TUG1 inhibited the level of BDNF by sponging miR-381-3p and antagonized its protective effect on neural repair in ICH rats. Our study suggests that TUG1 can sponge miR-381-3p to downregulate BDNF expression and inhibit neural repair following ICH, demonstrating a potential signaling pathway that is conducive to a better understanding of the pathological mechanisms of ICH. Show less
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adv Show more
Periodontal ligament stem cells (PDLSCs) hold great promise for periodontal regeneration therapy. However, their self-renewal and multilineage differentiation capabilities are often compromised by adverse factors in the periodontal microenvironment. Therefore, identifying novel therapeutic targets and elucidating the underlying molecular mechanisms to protect the proliferative and differentiation potential of PDLSCs is of significant importance. PDLSCs were exposed to electronic cigarette extract and various common oral stressors to evaluate the expression of glucagon such as peptide 1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR). PDLSCs isolated from patients with periodontitis and PDLSCs from a mouse periodontitis model were also analyzed. Functional studies were performed by GLP1R or GIPR knockdown, overexpression, and treatment with single or dual receptor agonists, followed by assessment of cell proliferation and multilineage differentiation capacities. Transcriptome (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and RNA immunoprecipitation sequencing (RIP-seq) were applied to delineate downstream signaling pathways and RNA–protein interactions. Protein synthesis regulation was further investigated by immunoprecipitation of interferon induced protein with tetratricopeptide repeats (IFIT)-associated translation initiation factors. For in vivo validation, wild-type and GLP1R/GIPR double-knockout periodontitis mice were transplanted with CRISPR-Cas9 mCherry-labeled PDLSCs and treated with receptor agonists. Disease severity and PDLSC fate were evaluated by histology and lineage tracing. Finally, a questionnaire-based survey was conducted in 150 patients with periodontitis, including 74 individuals with long-term use (> 1 month) of GLP1R or GLP1R/GIPR dual agonists (e.g., semaglutide, liraglutide, tirzepatide), to assess their periodontal outcomes. GLP1R and GIPR expression were markedly downregulated in PDLSCs exposed to multiple stressors and in PDLSCs isolated from periodontitis specimens. RNA-seq, ChIP-seq, and RIP-seq identified downstream pathways and RNA–protein interactions implicated in receptor-mediated regulation. Functionally, GIPR agonism promoted PDLSC proliferation via activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, whereas GLP1R agonist enhanced multilineage differentiation capacity in vitro. Mechanistically, GLP1R knockdown induced robust upregulation of IFIT1/2/3, while GLP1R agonist suppressed IFIT expression. IFIT1/2/3 were shown to interact with eIF3C and to inhibit translation of differentiation-related mRNAs, linking GLP1R signaling to translational control of PDLSC fate. In vivo, transplantation experiments in both wild-type and GLP1R/GIPR double-knockout periodontitis mice demonstrated that single and dual receptor agonists significantly improved endogenous and exogenous PDLSC-mediated periodontal regeneration. Consistently, a clinical survey of 150 patients with periodontitis (74 receiving GLP1R or dual agonists) revealed significantly better periodontal staging and grading in treated individuals, with longer agonist exposure associated with greater improvement. Our findings uncover the different molecular roles of GIPR and GLP1R in self-renewal capacity and multipotency of PDLSCs, and open new avenues for developing therapeutic targets and strategies in oral tissue engineering and regenerative medicine. The online version contains supplementary material available at 10.1186/s11658-026-00867-2. Show less
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don Show more
Pancreatic cancer (PC) is a common gastrointestinal malignancy whose initiation and progression may be closely linked to the gut microbiota. Previous research indicates that Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang (SB-SD) exhibit diverse biological activities, such as anti-inflammatory, antioxidant, and antitumor effects, though their precise regulatory mechanisms are not fully elucidated. Here, we treated PC cells with SB-SD to assess its impact on cell viability, apoptosis, migration, and cell cycle progression, while Western blotting analyzed the expression of HSP90AA1, MAPK3, p53, CDK1, and p21. We also established a pancreatic cancer xenograft model in nude mice to evaluate the in vivo inhibitory effect of SB-SD on tumor growth. Furthermore, we employed metagenomic sequencing, untargeted metabolomics, and quantitative proteomics to comprehensively profile changes in the gut microbiota, serum metabolites, and differentially expressed proteins, with Western blotting subsequently validating BCKDK, GATM and p53 expression. The results show that SB-SD significantly inhibited PC cell proliferation, promoted apoptosis, and induced S/G2 phase cell cycle arrest, potentially via modulation of the HSP90AA1/MAPK3 signaling pathway. Measurements of tumor volume and weight, complemented by histopathological analysis, confirmed that SB-SD effectively suppressed the growth of PANC-1 xenograft tumors. Integrated multi-omics analyses suggest that the antitumor effects of SB-SD may involve the modulation of key gut microbes like Bacteroides caccae and Lactobacillus, the promotion of choline metabolism, and the regulation of BCKDK and GATM. Together, these findings not only corroborate the direct antitumor activity of SB-SD against pancreatic cancer but also offer novel mechanistic insights by constructing a microbiota-metabolite-protein interaction network. Show less
Abdominal aortic aneurysm (AAA) is a chronic, inflammatory and degenerative vascular disease. Previous studies have demonstrated that stimulator of interferon genes (STING) is involved in multiple inf Show more
Abdominal aortic aneurysm (AAA) is a chronic, inflammatory and degenerative vascular disease. Previous studies have demonstrated that stimulator of interferon genes (STING) is involved in multiple inflammatory diseases. However, the role of STING in AAA formation and its possible mechanisms have yet to be investigated. Here, we investigated the role of STING in the development of AAA using two murine AAA models induced by porcine pancreatic elastase (PPE)/β-aminopropionitrile (BAPN) or angiotensin II (Ang II). The STING signaling pathway was significantly activated in AAA tissues from both mice and patients. Sting mutation slowed AAA formation, as confirmed by reduced AAA incidence, maximal abdominal aortic diameter, elastin disruption, collagen deposition, and inhibited immune cell infiltration in AAA mice. RNA-sequencing analysis revealed that compared with the control, Sting mutation inhibited inflammatory and immune responses in AAA tissues. Similar effects were observed after pharmacological inhibition of STING in Ang II infused ApoE Show less
Ischemic heart failure (IHF) is one of the leading causes of death in the world. Plasma apolipoprotein C3 (ApoC3) levels are significantly elevated in patients with heart failure and positively associ Show more
Ischemic heart failure (IHF) is one of the leading causes of death in the world. Plasma apolipoprotein C3 (ApoC3) levels are significantly elevated in patients with heart failure and positively associated with the incidence of ischemic heart disease (IHD). However, the causal association between ApoC3 and IHD development is unclear. ApoC3 expression changes were assessed in plasma from IHF patients/healthy donors and cardiac tissue from rodent models. 10-week-old male human ApoC3 transgenic (ApoC3 Overexpression of human ApoC3 in ApoC3 ApoC3 overexpression could activate cardiac TLR2/NF-κB to trigger the inflammation, oxidation, and apoptosis pathways, finally aggravating IHF in mice. Inactivation of ApoC3 could significantly alleviate IHF in hamsters. Show less
The increasing prevalence of age-related osteoporosis has emerged as a critical public health issue in the context of the globally aging population. Chronic oxidative stress, induced by excessive reac Show more
The increasing prevalence of age-related osteoporosis has emerged as a critical public health issue in the context of the globally aging population. Chronic oxidative stress, induced by excessive reactive oxygen species (ROS) associated with aging, is a critical factor underlying the development of osteoporosis in elderly individuals and a diminished capacity for bone formation and osteogenic differentiation. However, the mechanism underlying age-related osteoporosis remains unclear. MACF1 (microtubule actin crosslinking factor 1) is an essential factor that regulates bone formation and development, and exhibits reduced expression as humans age. In this study, we used MACF1 conditional knockout (MACF1-cKO) mice as a premature aging model and found that MACF1-cKO mice exhibited chronic oxidative stress. Moreover, the expression level, nuclear translocation, and transcriptional activity of FoxO1 were promoted in MACF1 deficient osteoblastic cells. In addition, the binding of FoxO1 to β-catenin was enhanced, increasing the transcriptional activity of the FoxO1/β-catenin pathway in MACF1 deficient osteoblastic cells. The enhanced FoxO1/β-catenin pathway competitively weakens the binding of β-catenin to TCF7 and decreases the activity of the TCF7/β-catenin pathway. Our study showed that FoxO1 responded to chronic oxidative stress induced by MACF1 deficiency to determine β-catenin fate and regulate osteoblast differentiation during senile osteoporosis. Show less
We developed a viscosity-activated near-infrared (NIR) fluorescent probe, QV-S. This probe features a long emission wavelength (815 nm), a large Stokes shift (135 nm), high viscosity sensitivity (431- Show more
We developed a viscosity-activated near-infrared (NIR) fluorescent probe, QV-S. This probe features a long emission wavelength (815 nm), a large Stokes shift (135 nm), high viscosity sensitivity (431-fold signal enhancement), and specific lysosome-targeting capability. QV-S allows for not only real-time monitoring of lysosomal viscosity changes in inflammatory and foam cells but also the precise imaging of atherosclerotic plaques in the aortas of ApoE Show less
The agreement between plasma Aβ42/40 and Aβ positron emission tomography (PET) is approximately 75 %, with ∼85 % of discrepancies due to positive plasma but negative PET results. It is unclear whether Show more
The agreement between plasma Aβ42/40 and Aβ positron emission tomography (PET) is approximately 75 %, with ∼85 % of discrepancies due to positive plasma but negative PET results. It is unclear whether this reflects Aβ changes in plasma before PET-detectable. To assess the influence of Aβ42/40 positivity on risk of progression to Aβ PET positivity, and feasibility of using plasma Aβ42/40 tests to enrich a primary prevention trial. A prospective longitudinal cohort study. Participants of Australian Imaging, Biomarkers and Lifestyle study (AIBL), Alzheimer's Disease Neuroimaging Initiative (ADNI), and Open Access Series of Imaging Studies 3 (OASIS3). 507 cognitively unimpaired adults at baseline, with a baseline Aβ PET < 20 Centiloid (CL) and available longitudinal Aβ PET data. Baseline Aβ PET and plasma Aβ42/40 measurement by mass-spectrometry, followed by 1-6 additional Aβ PET scans every 1.5-3 years. Those < 5 CL were classified as PET- and 5-20 CL as PET At baseline, 283 were Plasma-/PET-, 97 Plasma+/PET-, 76 Plasma-/PET Cognitively unimpaired individuals with abnormal Aβ42/40 are at increased risk for future Aβ PET positivity. In the 5-20 CL subgroup, baseline CL is the main driver of this risk. Combining blood-based pre-screening with PET imaging may help efficiently enrich primary prevention trials. Show less
The quality of informal care for people with dementia (PwD) has gained increasing importance, as most PwD prefer home-based care over institutional placement. However, evidence-based intervention prog Show more
The quality of informal care for people with dementia (PwD) has gained increasing importance, as most PwD prefer home-based care over institutional placement. However, evidence-based intervention programs tailored to distinct care quality profiles remain limited. Additionally, the absence of clear thresholds to identify PwD receiving low-quality informal care poses a challenge for research and clinical practice. Thus, this study aimed to identify the profiles of quality of care (QoC) among informal caregivers of PwD, explore influencing factors of different profile, and determine the optimal cut-off score of the Exemplary Care Scale (ECS). A cross-sectional survey was conducted. A total of 213 dyads of PwD and their informal caregivers were recruited from memory clinic, rehabilitation clinic, and neurological clinic of a tertiary hospitals and communities in Wuhan, Hubei, China, between July 15, 2023, and July 14, 2024. Latent profile analysis (LPA) was employed to identify QoC profiles. Multinomial logistic regression was performed to explore influencing factors of profile membership. Receiver Operating Characteristic (ROC) analysis was conducted to determine the ECS cut-off score. Three distinct QoC profiles were identified: high (24.41%), moderate (44.60%), and low (30.99%). Among informal caregivers, lower monthly income, insufficient social support, and higher perceived overload were associated with low QoC profile, whereas, better quality of pre-illness relationship with PwD and greater activities of daily living (ADL) of PwD were associated with high QoC. ROC analysis yielded an optimal ECS cut‑off score of 15, with high sensitivity (0.993) and specificity (0.955). This study identified three distinct QoC profiles among caregivers of PwD, underscoring the heterogeneity of informal care quality. The identified predictors and the validated ECS cut‑off score of 15 provide an empirical basis for developing tailored screening tools and targeted interventions for high‑risk caregiver subgroups. Show less