Alcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal-related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may Show more
Alcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal-related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may modulate alcohol-related behaviors. We investigated the effects of pitolisant, an FDA-approved H3R antagonist, on ethanol (EtOH)-related behaviors in mice. Adult male C57BL/6J mice underwent acute or chronic (2 or > 8 weeks) intermittent alcohol exposure. Pitolisant pretreatment was administered, and then pharmacological behavior, histologic, and molecular assays were conducted. Pitolisant administration reduced acute EtOH-induced locomotor activation, conditioned place preference, and sedative effects, and also curtailed EtOH intake. It alleviated anxiety and depression-like behavior during 24-h withdrawal (Post-EtOH). Mechanistically, the Post-EtOH condition was featured by complicated brain cFos expression mapping, including elevated cFos, [HA] and [glutamine]/[glutamate] ratio in the lateral habenula (LHb). However, systemic pitolisant treatment significantly increased [norepinephrine]/[normetanephrine] ratio, and restored the diminished phosphorylated CREB and BDNF levels in the LHb. Intra-LHb H2R antagonist cimetidine infusion partly blocked the pitolisant therapeutic effect on alcohol-related behavior. These findings highlight the HAergic system as a critical regulator of alcohol-related behaviors. The LHb HA signaling and norepinephrine neurotransmission might underlie pitolisant's potential novel therapeutic strategy for AUD. Show less
Dual GIP/GLP-1 receptor agonists have gained significant attention in clinical applications because of their remarkable efficacy in reducing obesity and type 2 diabetes. However, the mechanisms by whi Show more
Dual GIP/GLP-1 receptor agonists have gained significant attention in clinical applications because of their remarkable efficacy in reducing obesity and type 2 diabetes. However, the mechanisms by which these dual agonists affect systemic metabolism remain elusive. To investigate the effects of a novel dual-receptor agonist, THDBH120, on systemic metabolism in obese individuals and the specific roles of GIPR and GLP-1R in modulating systemic and adipose tissue metabolism. To evaluate the intrinsic properties of THDBH120, we conducted a potency assay by using HEK293 cell lines overexpressing either human GIPR or GLP-1R and measured the accumulation of cAMP as a downstream second messenger following receptor activation. To evaluate the efficacy of THDBH120 on systemic metabolism, we used obese rodents and nonhuman primate species that received various doses and frequencies of THDBH120. To determine the metabolic roles of GLP-1R and GIPR in mediating the beneficial effects of THDBH120, we used GLP-1R- and GIPR-knockout mouse models treated with THDBH120, the GLP-1R agonist semaglutide, or the GIPR agonist LAGIPRA and performed transcriptomic sequencing analyses of adipose tissues. THDBH120 is a novel long-acting dual GIPR/GLP-1R agonist that has superior weight loss and metabolic improvement effects in rodents and mammals. The activation of GLP-1R by semaglutide or THDBH120 improved lipid metabolism, whereas the activation of GIPR by LAGIPRA or THDBH120 alleviated inflammation. THDBH120 improved lipid metabolism via GLP-1R-mediated pathways and mitigated inflammation by activating GIPR-associated pathways in the adipose tissues of obese mice. Both GLP-1R and GIPR are important in mediating the beneficial effects of dual receptors on systemic metabolism. THDBH120 is a novel long-acting dual GIPR/GLP-1R agonist that has potential clinical applications. Show less
Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with hypercholesterolemia serving as a critical driver of atherogenesis. Although current lipid-lowering therapies Show more
Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with hypercholesterolemia serving as a critical driver of atherogenesis. Although current lipid-lowering therapies substantially improve circulating lipid profiles, strategies that provide more durable, safe, and efficient control of lipid metabolism are still needed. Epigenome editing offers a promising approach for long-lasting repression of disease-modifying genes without altering the underlying DNA sequence. Here, we develop CRISPRoff platforms delivered by adeno-associated virus or lipid nanoparticle to epigenetically silence hepatic Hmgcr or Pcsk9 in vivo. In both C57BL/6J wild-type and ApoE Show less
The bioactive peptide setmelanotide is a validated MC4R agonist, yet its clinical utility is constrained by poor aqueous solubility and dose-limiting, off-target hyperpigmentation. To overcome these d Show more
The bioactive peptide setmelanotide is a validated MC4R agonist, yet its clinical utility is constrained by poor aqueous solubility and dose-limiting, off-target hyperpigmentation. To overcome these dual liabilities, we executed a synergistic optimization strategy guided by detailed SAR investigation. This approach unveiled two critical design principles: a C-terminal "cationic imperative", where lysine uniquely conferred a > 20-fold solubility enhancement while retaining potency, and rational manipulation of the core pharmacophore, which imparted >100-fold selectivity over MC1R/MC3R. This synergy yielded the lead compound SC19, which integrates these features into a balanced profile of sub-nanomolar potency (EC₅₀ = 0.12 nM; pEC₅₀ = 9.93), exceptional selectivity, and high aqueous solubility. In a diet-induced obesity model, SC19 demonstrated robust efficacy comparable to setmelanotide in reducing weight gain and improving lipid profiles, affirming its therapeutic potential. This work not only presents a promising lead compound but also validates a synergistic optimization blueprint for concurrently enhancing the pharmacological and drug-like properties of therapeutic peptides. Show less
With the rapid progression of global population aging, the incidence of cognitive dysfunction-related disorders is steadily increasing. In recent years, growing attention has been directed toward the Show more
With the rapid progression of global population aging, the incidence of cognitive dysfunction-related disorders is steadily increasing. In recent years, growing attention has been directed toward the interaction between the gut microbiota and the central nervous system (CNS). The gut-brain axis (GBA), as a bidirectional communication pathway, plays an increasingly recognized role in regulating cognitive functions. Ganoderma lucidum polysaccharides (GLP), a traditional medicinal and edible substance, can regulate gut microbiota homeostasis and short-chain fatty acid (SCFAs) levels through the GBA. GLP reduces the Firmicutes/Bacteroidetes ratio, significantly increases the abundance of Lactobacillus, and further suppresses oxidative stress and inflammatory responses by controlling microglial overactivation and neuroinflammation, thereby enhancing the expression of synapse-associated proteins and brain-derived neurotrophic factor (BDNF). Consequently, GLP shows potential for improving cognitive dysfunction. This review systematically summarizes the bioactivities of GLP, explores the neurodegenerative mechanisms of aging, and proposes the possibility that GLP mitigates aging-induced inflammation and improves cognitive function via modulation of the gut microbiota. Show less
In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly r Show more
In recent years, except for the well-known heart failure with reduced ejection fraction (HFrEF), the incidence of heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) among the classification of heart failure (HF) has been increasing. However, due to their complex mechanisms, current research remains insufficient to address clinical needs. Utilizing wild-type (WT), miR-30a-5p knockout (KO), and overexpression (OE) murine models combined with estrogen modulation and ovariectomy (OVX), this study delineates sex-specific regulatory networks in HF pathogenesis. Female KO mice lost the inherent resistance of WT females to HFpEF induction via 24-week HFD/L-NAME, whereas males exhibited comparable HFpEF susceptibility regardless of genotype, developing hallmark phenotypes including diastolic dysfunction (E/E'), myocardial hypertrophy (heart weight/tibia length), cardiac fibrosis, and hepatic steatosis. Particularly, due to the reduced ejection fraction in KO mice, combined with HFD/L-NAME, the HF phenotype was ultimately manifested as impaired diastolic function and slightly reduced ejection fraction (with the characteristics of HFpEF and HFmrEF). Mechanistically, KO-HF females displayed significant estrogen axis disruption (plasma estradiol and the expression of ERα, ERβ, ESRRA, and PELP1 expression). OVX in WT females validated the importance of estrogen for HFpEF resistance. Transcriptomic profiling identified convergent targets across cardiac (ITGAD, ITGAM, FGA, and FGB) and hepatic tissues (APOA1 and APOB), revealing miR-30a-5p's orchestration of extracellular matrix remodeling (via ITGAD/ITGAM mechanotransduction),fibrinogen-mediated microvascular homeostasis, and APOB-driven metabolic dysregulation. Notably, OE intervention failed to mitigate OVX-induced cardiac/hepatic pathology, implicating estrogen-dependent miR-30a-5p functionality. These findings establish miR-30a-5p as a crucial sex-specific regulator of HF (mainly HFpEF), operating through estrogen signaling to balance cardiac compliance and metabolic adaptation. Show less
Diabetic foot ulcers (DFU) are a severe complication of diabetes. Although dysregulated M2 macrophage polarization is recognized as a key driver of chronic inflammation in DFU, the molecular checkpoin Show more
Diabetic foot ulcers (DFU) are a severe complication of diabetes. Although dysregulated M2 macrophage polarization is recognized as a key driver of chronic inflammation in DFU, the molecular checkpoints that can be therapeutically targeted to restore M2 bias remain poorly defined. Here, we aimed to determine whether the RNA-binding protein TAF15 acts as a post-transcriptional stabilizer of the M2-promoting CEBPB/APOE/PTX3 axis, thereby accelerating DFU healing. First, we confirmed that APOE positively regulates PTX3, which supports M2 polarization and the proliferation and migration of HDF. CEBPB transcriptionally activated APOE and promoted M2 macrophage polarization. TAF15 stabilized CEBPB mRNA and affected HDF cell proliferation and migration by promoting M2 macrophage polarization. Additionally, TAF15 overexpression partially counteracted the disruption of M2 macrophage polarization caused by APOE silencing and facilitated DFU wound healing. Collectively, our findings establish TAF15-driven stabilization of CEBPB mRNA as a target point that sequentially activates APOE/PTX3 signaling to enforce M2 polarization and accelerate DFU closure. This study provides a preclinical rationale for the development of TAF15-targeted oligonucleotides or small-molecule strategies to reprogram wound macrophages and improve DFU outcomes in patients with diabetes. Show less
Ting Fang, Xinyu Yang, Xiaoqing Deng+5 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Excessive fructose intake is strongly associated with metabolic diseases, with the carbohydrate response element-binding protein (ChREBP) playing a key role in its metabolism, particularly in renal tu Show more
Excessive fructose intake is strongly associated with metabolic diseases, with the carbohydrate response element-binding protein (ChREBP) playing a key role in its metabolism, particularly in renal tubules. However, the role of its active form, ChREBP-β, was previously unclear. In this study, ChREBP-β overexpression and ChREBP knockout mouse models were utilized to investigate the effects of excessive fructose intake in vivo. In addition, primary renal tubular epithelial cells from mice and human kidney-2 (HK2) cells were applied for further validation in vitro. We found that ChREBP-β leads to increased transcription to mediate endoplasmic reticulum stress and mitochondrial dysfunction, which ultimately impairs renal function. Our findings underscore the critical role of ChREBP-β in fructose-related renal disorders. 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
Bone angiogenesis is important for bone formation and regeneration after bone injury. Endothelial-derived angiogenic factors are key signal transducers in the bone microenvironment and maintain vascul Show more
Bone angiogenesis is important for bone formation and regeneration after bone injury. Endothelial-derived angiogenic factors are key signal transducers in the bone microenvironment and maintain vascular-osteogenic coupling during bone regeneration. CGRP, a bone sensory neuron-derived peptide, contributes to bone formation, but the potential mechanism by which it improves bone regeneration via angiogenesis is unclear. Here, we demonstrate that CGRP may contribute to bone repair in the elderly, as human CGRP levels are inversely proportional to age and proportional to bone mass in clinical data and bulk transcriptome data. Based on single-cell RNA sequencing data and experimental analyses, CGRP is found to promote the angiogenesis of human microvascular endothelial cell line-1 in vitro through the FAK-AKT-VEGF pathway. CGRP gene deletion in mice reduced bone vascular density and bone mass, and delayed angiogenesis and bone regeneration at the bone defect site. Recombinant CGRP restored bone repair after defect introduction. It also promoted Angptl4 secretion by bone vascular endothelial cells, thereby driving osteogenic differentiation of bone marrow mesenchymal stem cells and enhancing bone regeneration after bone injury. Treatment with recombinant Angptl4 enhanced bone healing in a mouse bone defect model. These integrated analysis reveal the important role and mechanism of CGRP in vascular-mediated osteogenesis, suggesting a novel therapeutic strategy for promoting bone regeneration. Show less
Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfun Show more
Corneal transparency maintenance relies on the water-pumping function of the corneal endothelium. Currently, corneal transplantation remains the only available treatment for corneal endothelial dysfunction, therefore, the development of alternative therapies is critical due to the global shortage of donor corneas. In our previous study, we confirmed that corneal stromal cells (CSCs) secretion can promote corneal endothelial cells (CEnCs) proliferation. This effect can be enhanced by treatment with lysophosphatidic acid (LPA), a bioactive phospholipid. Nevertheless, the components involved in CSC secretion remain to be elucidated. In this study, we investigated the therapeutic potential of CSC-derived exosomes and exosomal microRNAs (miRNAs) for enhancing CEnCs proliferation and corneal endothelial healing. CSC exosomes were characterized via nanoparticle tracking (NTA), transmission electron microscopy (TEM), and immunoassays. The miRNA expression profiles of CSC exosomes were identified via RNA sequencing, revealing a total of 767 distinct miRNAs. The proliferative effects of CSC exosomes and exosomal miR-221-3p were increased by LPA. Ectopic expression of miR-221-3p further increased CEnC proliferation and suppressed the expression of the CDK inhibitor p27 Show less
FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms rema Show more
FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms remain incompletely understood. Here, we report that cerebral FURIN-deficient mice exhibit cognitive decline and neurodegeneration. Lipid droplets (LDs) that are preferentially accumulated in astrocytes correlate with an increase of the LD markers PLIN2 and PLIN3, and conversely a decreased level of autophagic proteins including ATG5, BECN1 and MAP1LC3/LC3 as well as LAMP1. Accordingly, silencing of Show less
To investigate longitudinal changes in neuroimmune biomarkers during acute exacerbations of chronic obstructive pulmonary disease (AECOPD), their modulation by standard therapy, and prognostic implica Show more
To investigate longitudinal changes in neuroimmune biomarkers during acute exacerbations of chronic obstructive pulmonary disease (AECOPD), their modulation by standard therapy, and prognostic implications for 90-day outcomes. In a prospective cohort, 266 hospitalized AECOPD patients were stratified into worsened ( Compared with controls, AECOPD patients exhibited higher IL-6, TNF-α, PD-1, and MMP-9, alongside reduced BDNF and IL-10. Stable patients demonstrated partial biomarker normalization, whereas worsened patients retained a pro-inflammatory profile. Corticosteroids and antibiotics attenuated cytokine elevations, and oxygen therapy facilitated BDNF recovery. Low BDNF and high MMP-9 predicted spirometric decline, while elevated PD-1 and MMP-9 were associated with increased 90-day readmission risk. A dual-axis model incorporating neurotrophic and immune exhaustion markers outperformed GOLD classification for risk prediction. Neuroimmune biomarkers capture recovery heterogeneity in AECOPD. The proposed dual-axis model improves prognostic accuracy and may inform personalized management strategies. Show less
Hepatocellular carcinoma (HCC) exhibits high recurrence rates and limited therapeutic options. Endothelial cell-specific molecule 1 (ESM1) and angiopoietin-like 4 (ANGPTL4) are implicated in tumor pro Show more
Hepatocellular carcinoma (HCC) exhibits high recurrence rates and limited therapeutic options. Endothelial cell-specific molecule 1 (ESM1) and angiopoietin-like 4 (ANGPTL4) are implicated in tumor progression, yet their synergistic role in HCC lipid metabolism and angiogenesis remains unexplored. We integrated multi-omics approaches, including RNA sequencing, metabolomics, and immunoprecipitation-mass spectrometry, in HCC cell lines and patient-derived xenograft models. Key experiments involved Co-IP, Western blotting, tube formation assays, and clinical tissue microarray analysis to validate the ESM1-ANGPTL4-FASN-trioleate axis. ESM1 and ANGPTL4 formed a positive feedback loop, stabilizing fatty acid synthase (FASN) to promote trioleate synthesis. Trioleate activated the NF-κB/IL-17 pathway in HCC cells and upregulated CD99 in endothelial cells, driving angiogenesis. In vivo, ESM1/ANGPTL4 knockdown suppressed tumor growth, which was rescued by trioleate supplementation. Clinical data revealed elevated ESM1/ANGPTL4 expression in bevacizumab-resistant HCC, correlating with poor prognosis. The ESM1-ANGPTL4-FASN-trioleate axis orchestrates metabolic reprogramming and endothelial activation, representing a promising therapeutic target. Future studies should explore combination therapies targeting this axis and overcoming bevacizumab resistance in HCC. Show less
Hemodialysis, as one of the main alternative treatment methods for end-stage renal disease, has received much attention in recent years. Due to the particularity of hemodialysis treatment, patients ha Show more
Hemodialysis, as one of the main alternative treatment methods for end-stage renal disease, has received much attention in recent years. Due to the particularity of hemodialysis treatment, patients have a relatively high risk of infection during the treatment process. Hemodialysis nurses, who are the main executors of the treatment operations and have the most contact with patients, have a close relationship with the infection risk of patients. The level of their hospital infection prevention and control literacy is closely related to the infection risk of patients. To explore the current level of knowledge, attitudes, and practices (KAP) of hospital infection prevention and control among haemodialysis nurses in the Sichuan Province, China, and identified their potential categories. This provided evidence-based recommendations for improving infection control management in hemodialysis departments. A cross-sectional study was conducted From July 15 to August 15, 2025 using a convenience sampling method to survey 470 hemodialysis nurses from 78 hospitals in Sichuan Province. Participants were licensed nurses with over 3 months of hemodialysis experience. Data were collected using the A total of 460 valid questionnaires were collected, with an effective response rate of 97.87%. The average scores for knowledge, attitudes, and practices related to hospital infection prevention and control among haemodialysis nurses were 4.67 ± 0.43, 4.59 ± 0.43, and 4.74 ± 0.34, respectively. Three latent profile models were constructed, with the two-class model identified as the optimal solution, which were defined as the "Low KAP Group" (25.9%) and "High KAP Group" (74.1%). Logistic regression analysis revealed that sex, responsibility for infection control, hospital level, annual number of infection control training sessions, organizational support, and work engagement were significant influencing factors ( The KAP level of haemodialysis nurses in hospital infection prevention and control was relatively high. Hospital managers should tailor supportive work environments on the basis of the individual characteristics and work engagement of haemodialysis nurses to improve the KAP level of nosocomial infection prevention and control among haemodialysis nurses. Show less
Neuropathic pain (NP) is a debilitating condition with limited treatment options. The ethanolic extract of Bauhinia brachycarpa Benth (EEBb) has demonstrated antinociceptive effects in NP, but its act Show more
Neuropathic pain (NP) is a debilitating condition with limited treatment options. The ethanolic extract of Bauhinia brachycarpa Benth (EEBb) has demonstrated antinociceptive effects in NP, but its active components and underlying mechanisms of action remain largely unexplored. Bauhinia brachycarpa Benth (BBB), an ethnic medicine in China, has antinociceptive effect on neuropathic pain (NP). In this study, an effective portion from BBB was screened and its antinociceptive mechanism was investigated. After the preparation of ethanolic extract from BBB (EEBb) and different soluble portion from EEBb (peEEBb, eaEEBb, nbEEBb), the total content of flavonoids and phenolic acids were measured. A partial sciatic nerve ligation (PSNL) model in vivo was applied to evaluate the antinociceptive effect and the influence on microglia function of these samples. The possible acting target of BBB was predicted by network pharmacology. And the mechanism of nbEEBb, the most effective antinociceptive portion, were studied by PSNL model in vivo and ATP-induced activation of BV2 model in vitro. nbEEBb had the strongest ability of alleviating NP as well as the obvious effect on microglia polarization. The action of nbEEBb was positively correlated to the total content of flavonoids or phenolic acids. nbEEBb inhibited the protein and gene expressions of most key components in P2X4-BDNF-TrkB signaling pathway. nbEEBb is the most effective portion from BBB on NP, and its mechanism refers to the inhibition of P2X4-BDNF-TrkB signaling pathway, which involved in neuron-microglia interaction. Show less
Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to c Show more
Fusion genes are pivotal drivers of tumorigenesis, often generating oncogenic chimeric RNAs and fusion circular RNAs. However, the mechanisms by which these transcripts synergistically contribute to cancer progression remain poorly understood. Here, we identified a lung cancer-specific chimeric RNA KANSL1-ARL17A (chKANSARL) and its circular variant fusion circular RNA KANSL1-ARL17 A (F-circKA), both derived from the fusion gene KANSARL. Functional assays revealed that overexpression of either chKANSARL or F-circKA significantly enhanced lung cancer cell proliferation, migration, and invasion, while their knockdown suppressed these malignant phenotypes. In vivo experiments demonstrated that chKANSARL overexpression accelerated tumor growth in immunodeficient mice. Notably, coexpression experiments uncovered a synergistic regulatory interaction between F-circKA and chKANSARL, amplifying oncogenic effects. Mechanistically, miRNA sequencing and dual-luciferase assays revealed that F-circKA acts as a molecular sponge for miR-6860, thereby derepressing chKANSARL expression. Rescue experiments further validated this regulatory axis, wherein miR-6860 inhibition reversed the tumor-suppressive effects of F-circKA knockdown. Collectively, our study identifies and characterizes a novel F-circKA/miR-6860/chKANSARL regulatory axis, revealing how dual transcriptional outputs from the KANSARL fusion gene can synergistically drive lung cancer progression. These findings highlight a previously unrecognized layer of cooperative regulation between linear and circular fusion RNAs in oncogenesis and provide a new framework for understanding fusion gene-mediated tumorigenesis. Show less
Wenyu Gao, Hao Chen, Fangyu Lin+7 more · 2026 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
Gastric cancer (GC) is a leading cause of cancer-related deaths and has high recurrence rate. Although fibronectin domain-containing protein 1 (FNDC1) is implicated in GC progression, its molecular me Show more
Gastric cancer (GC) is a leading cause of cancer-related deaths and has high recurrence rate. Although fibronectin domain-containing protein 1 (FNDC1) is implicated in GC progression, its molecular mechanisms remain unclear. Multi-omics analyses (TCGA, GEO datasets) were used to assess FNDC1 expression and clinical correlation. In vitro (cell proliferation, invasion, EMT markers) and in vivo (xenograft) experiments, combined with molecular assays (Co-IP, WB, ChIP), explored FNDC1's function and mechanism. FNDC1 was significantly upregulated in GC, correlating with advanced clinicopathological features and poor prognosis. Knockdown of FNDC1 suppressed GC cell proliferation, invasion, and metastasis by inhibiting EMT and Wnt/β-catenin signaling. Mechanistically, FNDC1 competitively bound the WD5 domain (residues 224-254) of Gβ2, disrupting Gβγ-Dvl1 interaction. This prevented Dvl1 degradation, promoted Axin1 ubiquitination, and destabilized the β-catenin-destruction complex (GSK3 β-APC-Axin1), leading to β-catenin accumulation and Wnt pathway activation. FNDC1 drives GC malignancy by targeting the Gβ2-Dvl1 axis to activate Wnt/β-catenin signaling, suggesting FNDC1 as a novel prognostic biomarker and therapeutic target. Show less
Given the heterogeneous nature of Alzheimer's disease (AD) and its higher prevalence in females, it is crucial to understand sex-related differences in AD presentation and changes in the brain. This s Show more
Given the heterogeneous nature of Alzheimer's disease (AD) and its higher prevalence in females, it is crucial to understand sex-related differences in AD presentation and changes in the brain. This systematic review investigates sex differences in AD and summarizes key findings from neuroimaging studies over the past two decades to examine how genetics, hormones, and lifestyle factors influence neuroimaging biomarkers and their correlation with cognitive decline and AD progression. A comprehensive literature search was conducted across several databases for human studies from 2004 to 2024 related to AD, biological sex differences, and neuroimaging. After a 3-step review process, the final extraction included 120 peer-reviewed studies using various neuroimaging modalities, such as MRI, amyloid-beta PET, tau-PET, and fluorodeoxyglucose (FDG) PET, to investigate sex as a biological predictor variable in adults with or at risk for AD. Over 90% of the reviewed studies identified clear sex-specific patterns of imaging biomarkers related to cognitive reserve, hormonal changes, APOE-ɛ4 genotype, inflammation, vascular health, and lifestyle factors. Machine learning studies increasingly incorporate sex as a key variable, revealing sex-specific biomarkers and improving model performance in predicting disease status and progression. Considering biological sex in AD research is essential for improving diagnostic accuracy, tailoring interventions, and health outcomes. This systematic review identifies sex-specific patterns in neuroimaging biomarkers of AD, influenced by cognitive reserve, hormones, APOE-ɛ4 genotype, inflammation, vascular health, and lifestyle. Recognizing these differences is crucial for understanding, diagnosis, and treatment efficacy. Show less
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the ef Show more
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the effects of Orientin on oxidized low-density lipoprotein and high glucose (ox-LDL/HG)-triggered endothelial cell injury and diabetes-accelerated atherosclerosis remain unclear. ApoE Show less
Occupational stress in nursing is a critical issue that can have significant implications for both workforce stability and personal health. This study aimed to identify subgroups of occupational stres Show more
Occupational stress in nursing is a critical issue that can have significant implications for both workforce stability and personal health. This study aimed to identify subgroups of occupational stress among Chinese female clinical nurses using latent profile analysis, compare sociodemographic differences across these subgroups, and examine their associations with premenstrual syndrome (PMS). A cross-sectional study was conducted among female nurses in tertiary hospitals in Huai'an City, Jiangsu Province, China, from November to December 2023. We recruited participants via convenience sampling, and 400 valid questionnaires were collected. Data were collected using a researcher-developed general information questionnaire, the standardized Chinese Nurses Stressor Scale (35 items), and the Premenstrual Syndrome Scale. Latent profile analysis (LPA) was performed with Mplus 8.0 to identify occupational stress subtypes. Sociodemographic predictors of these subtypes were explored using chi-square tests and multivariate logistic regression in SPSS 25.0. The association between stress subtypes and PMS symptoms was assessed using ANOVA. A Three clinical female nurse occupational stress subtypes were identified: overall low-stress (38.3%, This study identified significant heterogeneity in occupational stress among clinical female nurses, categorized into three distinct subtypes differing in stress levels and demographic characteristics. These findings highlight the importance of considering individual differences when developing interventions to address occupational stress. The study advocates for the implementation of intervention strategies targeting different types of stress in nursing education and organizational reform to better support nurses in fulfilling their responsibilities. Show less
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonst Show more
Breast cancer (BC) progression is intricately linked to the dysregulation of transfer RNA-derived fragments (tRFs). Through comprehensive analysis of The Cancer Genome Atlas (TCGA) data, it is demonstrated that 5'tRF-GlyGCC is overexpressed in BC tissues and negatively associated with patients' survival. Mechanistically, 5'tRF-GlyGCC binds to lactate dehydrogenase A (LDHA), enhancing its enzymatic activity and promoting glycolysis, which drives BC cell malignancy. This binding is mediated by the phosphorylation of LDHA at tyrosine 10, and facilitated by fibroblast growth factor receptor 1 (FGFR1), through the formation of a ternary complex that amplifies oncogenic signaling. Furthermore, 5'tRF-GlyGCC/LDHA axis induces macrophage infiltration and polarization toward an M2 phenotype, mediated by the chemokine CCL7, thereby reshaping the tumor microenvironment. Additionally, it is uncovered that the biogenesis of 5'tRF-GlyGCC is regulated by ALKBH3 and ANG, which also modulate LDHA activity. In vivo, targeting 5'tRF-GlyGCC/LDHA signaling significantly suppresses tumor growth and enhances the efficacy of immunotherapy. Collectively, these findings elucidate the pivotal role of 5'tRF-GlyGCC in BC progression, highlighting its potential as therapeutic target for BC treatment. Show less
Depression has emerged as a concerning factor in colon cancer progression and treatment, yet its underlying mechanisms and therapeutic targets remain poorly defined. This study aimed to elucidate how Show more
Depression has emerged as a concerning factor in colon cancer progression and treatment, yet its underlying mechanisms and therapeutic targets remain poorly defined. This study aimed to elucidate how depression affects colon cancer progression and chemotherapeutic response, and to explore potential molecular targets and therapeutic interventions involving the traditional Chinese medicine formula Sinisan (SNS) and its bioactive component Quercetin. A mouse model combining depression and colon cancer was established to evaluate behavioral alterations, tumor progression, and pathological features. RNA sequencing was performed to screen the differentially expressed genes. The effects of corticosterone (CORT) on proliferation, colony formation, migration, and GSTM2 expression were examined in HCT116 cells, followed by functional validation through GSTM2 overexpression and inhibition assays. Molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) were used to validate the binding of Quercetin to GSTM2. The therapeutic efficacy of SNS and Quercetin was assessed with respect to depressive symptoms, serum BDNF levels, NLRP3 inflammasome activity, and the potency of 5-fluorouracil (5-FU) chemotherapy. Mice with depression and colon cancer exhibited aggravated depressive behaviors and accelerated tumor progression. RNA-sequencing and network pharmacology analyses identified GSTM2 as a promising candidate target in colon cancer treatment, which was markedly down-regulated in the DP-CC group. CORT enhanced proliferation, colony formation, and migration of HCT116 cells while simultaneously suppressing GSTM2 expression. Conversely, GSTM2 levels negatively correlated with cell proliferation, colony formation, and chemoresistance in HCT116 cells. Treatment with SNS alleviated depressive symptoms, elevated serum BDNF, reduced NLRP3 inflammasome activity, and potentiated the efficacy of 5-FU chemotherapy. Quercetin, a bioactive component of SNS, bound to GSTM2 through hydrogen-bond and van-der-Waals interactions, up-regulated GSTM2 expression, and mitigated CORT-induced proliferation, colony formation, and chemoresistance. Our findings suggest that depression promotes colon-cancer progression by down-regulating GSTM2, whereas SNS restores GSTM2 expression and enhances chemotherapeutic response. Show less
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with systemic manifestations, including cognitive impairment linked to gut‒brain axis dysregulation. While probiotic therapies show prom Show more
Ulcerative colitis (UC) is a chronic inflammatory bowel disease with systemic manifestations, including cognitive impairment linked to gut‒brain axis dysregulation. While probiotic therapies show promise, their mechanisms in mitigating neuropsychiatric comorbidities remain unclear. Here, we investigated the therapeutic potential of Show less
Gary Chen, Adrienne Sexton · 2026 · Patient education and counseling · Elsevier · added 2026-04-24
This scoping review aims to map the experiences and outcomes of patients and their families undergoing genetic testing and counseling regarding dementia to inform future research directions and clinic Show more
This scoping review aims to map the experiences and outcomes of patients and their families undergoing genetic testing and counseling regarding dementia to inform future research directions and clinical practice. Rigorous scoping review methodology was followed. Ovid Medline, Embase, PsycINFO, and CINAHL were searched with keywords and MeSH terms related to "genetic testing", "genetic counseling", "dementia", "decision making", and "patient outcomes" for peer-reviewed studies with adult participants published over the last ten years. Thirty-six articles met inclusion criteria. Narrative synthesis organized findings into temporal categories including motivations for genetic testing, experiences during the testing/counseling process, and outcomes after testing. Common motivators included reducing uncertainty, reproductive planning, life planning, and the prospect of a treatment becoming available in the future. A lack of current treatments and fear that knowledge of genetic risk would be difficult to cope with were common barriers to testing. Patient-centered communication improved satisfaction. Genetic testing was generally psychologically well tolerated, and a wide range of practical responses were reported including changes to lifestyle, diet, advanced care and financial planning, and engaging in clinical trials. This review maps the experiences and outcomes of genetic testing or counseling for people with or at potentially increased genetic risk of dementia. Genetic testing and counseling for directly causal dementia genes and APOE genotype appears well tolerated but long-term outcome data is lacking. Motivations, concerns and perceived benefits of knowing genetic results vary depending on personal, familial and cultural viewpoints. Genetic counseling can help patients and families prepare, reduce decisional regret, and adapt to results. Motivations varied, and a patient-centered approach addressing both information and psychological aspects improves satisfaction. Future longitudinal research should ascertain ways to support individuals from a wide range of demographics with understanding and adjusting to genetic risk information regarding dementia. Show less
Psoriasis and atopic dermatitis (AD) are two prevalent inflammatory skin disorders, each characterized by distinct adaptive immune responses. However, recent evidence suggests that these diseases may Show more
Psoriasis and atopic dermatitis (AD) are two prevalent inflammatory skin disorders, each characterized by distinct adaptive immune responses. However, recent evidence suggests that these diseases may share overlapping immune mechanisms, especially concerning keratinocyte function. The specific cytokines that coordinate these inflammatory pathways remain largely undefined. The expression of IL-27 and its receptor was analyzed using data derived from GEO datasets. Imiquimod-induced psoriasis-like and MC903-induced AD-like skin inflammation models were established in wild-type and Il27ra knockout littermates. Skin inflammation was evaluated using clinical scoring, histology, and immunostaining. Flow cytometry was employed to characterize immune cell populations in skin. Expression of relevant cytokines and signaling molecules was assessed using quantitative PCR, bulk RNA sequencing, and Western blotting. We found significantly elevated expression of the IL-27 receptor in the lesional skin of patients with psoriasis or AD. IL-27 receptor-deficient mice exhibited markedly reduced skin inflammation in both psoriasis-like and AD-like murine models. Mechanistic investigations revealed that IL-27 induces tumor necrosis factor-α production via signal transducer and activator of transcription 1 activation in keratinocytes, thereby potentiating inflammatory responses. Our findings identify IL-27 signaling in keratinocytes as a pivotal regulator of skin inflammation in both psoriasis and AD. This highlights IL-27 as a promising therapeutic target for inflammatory skin diseases. Show less
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Show more
Lecanemab, an anti-amyloid beta (Aβ) protofibril antibody, was introduced in China in 2024, but its real-world performance remains unknown. In this prospective, multicenter study across 21 sites, 261 Alzheimer's disease patients (mild cognitive impairment to moderate dementia) received biweekly lecanemab (10 mg/kg). A matched Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort served as comparator. Cognitive tests, plasma biomarkers, and optional amyloid/tau positron emission tomography (PET) were assessed over 6 months. Lecanemab significantly attenuated cognitive decline versus ADNI. Plasma Aβ42, Aβ40, phosphorylated tau 217 (p‑tau217), glial fibrillary acidic protein (GFAP), and ratios showed robust changes; a p‑tau217 reduction correlated with amyloid PET clearance (mean -22.1 Centiloid; 29.2% turned amyloid-negative). Apolipoprotein E (APOE) ε4 non-carriers showed greater improvements. Infusion reactions occurred in 11.1% and amyloid-related imaging abnormalities in 9.2% (1.6% symptomatic), with no stage-related safety differences. Lecanemab was effective and well tolerated in real-world Chinese patients. Plasma p‑tau217 may serve as a sensitive, minimally invasive treatment-response biomarker. Show less
This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and Show more
This study investigated the impact of This retrospective case-control study involved 628 CAD patients and 628 matched controls without CAD. ApoE genotyping was conducted using PCR-chip technology, and genotype and allele frequencies were compared between groups. Multivariate logistic regression analyzed the link between ApoE polymorphisms and CAD risk in populations at middle and high altitudes. The data revealed significant differences in These findings validated that the Show less
Brusatol (BRU), a major bioactive quassinoid isolated from Brucea javanica, has shown potential in the treatment of inflammatory diseases. As mitochondrial dysfunction has been implicated in chronic i Show more
Brusatol (BRU), a major bioactive quassinoid isolated from Brucea javanica, has shown potential in the treatment of inflammatory diseases. As mitochondrial dysfunction has been implicated in chronic inflammatory disorders, modulation of mitochondrial homeostasis may offer a potential approach for the treatment of rheumatoid arthritis (RA) and atherosclerosis (AS). To develop a novel BRU derivative through rational modification at the C11‑hydroxyl group and to compare the therapeutic effects of BRU and its derivative BRUD in experimental models of RA and AS, with particular focus on mitochondrial regulation and Drp1-associated signaling. This study combined in vivo and in vitro experiments to evaluate the pharmacological effects of BRU and BRUD and investigate the underlying mechanisms. The chemical constituents of BRU and BRUD were confirmed by HPLC and NMR spectroscopy ( In vivo studies demonstrated that both compounds ameliorated joint damage in CIA rats and reduced atherosclerotic lesion burden in ApoE These findings suggest that BRUD exhibits improved activity compared with BRU in RA and AS models, with protective effects associated with modulation of mitochondrial dysfunction, supporting its further evaluation as a lead compound. Show less
The polyphenols in grains are highly active, but some polyphenols in highland barley are in a bound form and have extremely low bioavailability. Fermentation by lactic acid bacteria (LAB) is capable o Show more
The polyphenols in grains are highly active, but some polyphenols in highland barley are in a bound form and have extremely low bioavailability. Fermentation by lactic acid bacteria (LAB) is capable of altering the functionality of foods. This research investigated the effects of fermentation with different LAB, such as Lactobacillus acidophilus (LAC), Lactobacillus casei (LCA), Lactobacillus rhamnosus (LRH), Lactobacillus plantarum (LPL), and Lactobacillus bulgaricus (LBU), on the hypoglycemic activity and mechanism of polyphenols in highland barley. The hypoglycemic activity of the fermentation products was measured by in vitro antioxidant, enzyme activity, and glucose consumption experiments. Untargeted metabolomic analysis used UHPLC-Q Exactive HF-X/MS to reveal distinct metabolic profiles among the fermented groups. Molecular docking and western blot experiments were conducted to elucidate the mechanism underlying the hypoglycemic effect of fermentation products. Polyphenolic antioxidant activity in highland barley and its inhibitory activities against α-glucosidase and α-amylase were increased after LAC fermentation. Furthermore, the fermented extracts improved glucose consumption in HepG2 cells. The content determination and metabolomic analysis showed that fermented highland barley polyphenols were increased, and 113 differential phenolic metabolites were identified and annotated, among which 44 exhibited a significant upregulation compared with raw highland barley polyphenols. At the molecular level, the polyphenol extract upregulated PI3K and phosphorylated Akt expression in HepG2 cells. Overall, the results indicate that fermentation by LAC biotransformed highland barley polyphenols into smaller molecules with improved hypoglycemic activities, thereby enhancing their bioavailability. Show less