Xiaokun Li, Zhiheng Rao, Wenhao Hu+2 more · 2025 · Obesity reviews : an official journal of the International Association for the Study of Obesity · Blackwell Publishing · added 2026-04-24
Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, e Show more
Metabolic dysfunction-associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, excess deposition of lipids in hepatic lipid droplets. Despite the growing prevalence and serious risks it poses, including liver decompensation, the need for transplantation, and increased patient mortality, MASH currently faces no approved pharmacotherapy. Several promising treatment candidates have emerged from recent clinical trials, including analogs of FGF21 and agonists of the associated FGFR1-KLB complex. These agents were well-tolerated in trials and have demonstrated significant improvements in both histological and biochemical markers of liver fat content, inflammation, injury, and fibrosis in patients with MASH. Endocrine FGF21 plays a vital role in maintaining homeostasis of lipid, glucose, and energy metabolism. It achieves this through pathways that target lipids or lipid droplets in adipocytes and hepatocytes. Mechanistically, pharmacological FGF21 acts as a potent catabolic factor to promote lipid or lipid droplet lipolysis, fatty acid oxidation, mitochondrial catabolic flux, and heat-dissipating energy expenditure, leading to effective clearance of hepatic and systemic gluco-lipotoxicity and inflammatory stress, thereby preventing obesity, diabetes, and MASH pathologies. In this review, we aim to provide an update on the outcomes of clinical trials for several FGF21 mimetics. We compare these outcomes with preclinical studies and offer a lipid-centric perspective on the mechanisms underlying the clinical benefits of these agents for MASH. Show less
Hui Wang, Timothy S Chang, Beth A Dombroski+64 more · 2025 · Movement disorders : official journal of the Movement Disorder Society · Wiley · added 2026-04-24
The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear pa Show more
Cardiovascular-kidney-metabolic (CKM) syndrome significantly increases cancer and mortality risks, but the combined effects of CKM syndrome and physical activity (PA) on these outcomes remain poorly u Show more
Cardiovascular-kidney-metabolic (CKM) syndrome significantly increases cancer and mortality risks, but the combined effects of CKM syndrome and physical activity (PA) on these outcomes remain poorly understood. This prospective study included 66,650 UK Biobank participants with accelerometry data. CKM syndrome was classified into five stages based on metabolic, kidney, and cardiovascular health. PA was categorized by intensity into light (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA) levels, and further divided into tertiles by daily duration. Multivariable Cox models were used to estimate hazard ratios. Over a median follow-up of 8.03 years, 4,301 incident cancer cases and 2,442 deaths occurred. Advancing CKM stages were associated with elevated risks of both cancer incidence and all cause mortality, while increasing PA levels reduced these risks. Significant interactions were observed between CKM syndrome and both MPA and MVPA on cancer and mortality risks (P interaction < 0.05). In participants with the lowest tertile of MPA or MVPA, those in stages 2 and 4 had higher cancer risk, while in the highest tertile, this risk was no longer elevated. For all-cause mortality, in participants with the lowest tertile of MPA or MVPA, CKM stage 3 exhibited higher risks, while those in the highest tertile did not. CKM stage 4 remained associated with higher mortality across all PA intensity levels, but risks decreased with increasing MVPA levels. Higher levels of MPA and MVPA may mitigate the elevated risks of both cancer incidence and all-cause mortality associated with CKM stages 2 to 4. Show less
Alzheimer's disease (AD) is a common progressive and irreversible neurodegenerative disease. AD accounts for 60%-70% of all dementia cases, ranking as the seventh leading cause of death globally. Huma Show more
Alzheimer's disease (AD) is a common progressive and irreversible neurodegenerative disease. AD accounts for 60%-70% of all dementia cases, ranking as the seventh leading cause of death globally. Human umbilical cord mesenchymal stem cells (hUC-MSCs) characterized by their abundant availability and low immunogenicity, have demonstrated significant therapeutic potential for AD in both preclinical studies and clinical trials. The use of exosomes can help mitigate the issues associated with cellular therapies. However, the clinical application of hUC-MSCs remains challenging due to their inability to effectively traverse the blood-brain barrier (BBB) and reach pathological sites. Therapeutic strategies utilizing exosomes derived from hUC-MSCs (Exos) have emerged as an effective approach for AD intervention. Here, we used ultrasound to construct multifunctional Exos (MsEVB@R/siRNA) for AD therapy. We obtained small interfering RNA for β-site precursor protein lyase-1 (BACE1 siRNA) and berberine for co-delivery into the brain. Berberine, a classical anti-inflammatory agent, effectively alleviates neuroinflammation in AD pathogenesis. BACE1 serves as the pivotal cleavage enzyme in amyloid β-protein (Aβ) formation, where silencing BACE1 synthesis through BACE1 siRNA significantly reduces Aβ production. In a 5xFAD mouse model, Exos selectively targeted microglial and neuronal cells after nasal delivery under the action of neural cell-targeting peptide rabies virus glycoprotein 29 (RVG29). BACE1 siRNA and berberine (BBR) loading enhanced the effectiveness of Exos in improving cognitive function, promoting nerve repair and regeneration, reducing inflammatory cytokine expression, and suppressing glial responses. BACE1 siRNA release was confirmed to reduce BACE1 expression and Aβ deposition. Concurrently, berberine effectively suppressed the release of inflammatory factors, thereby reducing neuroinflammation. In conclusion, the nasal delivery of engineered exosomes is a potentially effective method for treating AD. Show less
Juvenile hormone (JH) is important to maintain insect larval status; however, its cell membrane receptor has not been identified. Using the lepidopteran insect
The intrinsic heterogeneity and invasiveness of diffuse gliomas complicate accurate prognosis. Existing approaches are largely constrained by subtype specificity or limited analytical dimensions. To a Show more
The intrinsic heterogeneity and invasiveness of diffuse gliomas complicate accurate prognosis. Existing approaches are largely constrained by subtype specificity or limited analytical dimensions. To address this gap, a multi- dimension-based prognostic framework encompassing the full glioma spectrum was developed, accompanied by an analysis of the associated immune microenvironment. A total of 3,323 glioma samples from the SEER (n = 2181), CGGA (n = 807), and TCGA (n = 335) datasets were integrated. Differentially expressed genes were screened using the limma package, and a Lasso-Cox-based prognostic signature (Glioma-GDPM) was established. Clinical variables such as age, grade, and IDH mutation status were harmonized through propensity score matching to construct a multi-omics prognostic model (Glioma-GCDPM). GSEA, CIBERSORT-based immune infiltration analysis, and TIDE scoring were used to investigate the biological characteristics of different risk subgroups. Eleven key prognostic genes (such as PRAMEF2 and FADS1) and four clinical factors (age, tumor grade, IDH mutation, and 1p/19q codeletion) were identified. Glioma-GCDPM demonstrated favorable predictive ability in both the internal test cohort (AUC 0.81-0.86) and external validation sets (AUC 0.59-0.83). High-risk tumors exhibited greater invasiveness, with significant enrichment in cell cycle and proliferation-associated pathways. Additionally, a suppressed immune microenvironment was observed, reflected by elevated M2 macrophage infiltration and increased T cell dysfunction scores. The multi-omics model established in this study enables precise stratification of prognostic risk in diffuse glioma patients and reveals immunosuppressive features in high-risk individuals, providing a new basis for personalized treatment strategies. Show less
This study investigates the effect of angiopoietin-like 4 (ANGPTL4) on allergic rhinitis (AR) and explores the underlying mechanisms. A mouse model of AR was generated through ovalbumin (OVA) challeng Show more
This study investigates the effect of angiopoietin-like 4 (ANGPTL4) on allergic rhinitis (AR) and explores the underlying mechanisms. A mouse model of AR was generated through ovalbumin (OVA) challenge. The numbers of nasal rubbing and sneezing were counted and scored. Histological staining was conducted to analyze pathological alterations and inflammation in the mouse nasal mucosa. Inflammatory cytokines in serum and nasal lavage fluid (NALF) samples were analyzed using ELISA kits. Populations of regulatory T cells (Tregs) and Th17 cells in NALF or lymph nodes were analyzed using flow cytometry. Mice with AR were administered short hairpin (sh) RNAs targeting ANGPTL4. The effect of Notch pathway in AR severity was analyzed by gain- and loss-of-function assays. The consistent OVA challenge led to significant AR-like symptoms in mice, along with increased Notch signaling activation. Inhibiting this pathway using γ-secretase inhibitor (DAPT) markedly reduced the AR scores and alleviated inflammatory infiltration by improving Treg/Th17 cell balance. ANGPTL4 silencing significantly mitigated AR-related symptoms, Treg/Th17 cell imbalance, and inflammatory cascades in mice by inactivating the Notch signaling pathway. However, these alleviating effects of ANGPTL4 silencing on mice were negated by the administration of valproic acid, an agonist of the Notch signaling. This paper provides evidence that the ANGPTL4 knockdown shows significant therapeutic effects on AR by improving the Treg/Th17 cell balancing, effects achieved, at least in part, by blocking the Notch signaling pathway. Show less
Halide perovskite nanomaterials have emerged as a transformative platform for generating and manipulating polarized luminescence, offering unprecedented opportunities for next-generation optoelectroni Show more
Halide perovskite nanomaterials have emerged as a transformative platform for generating and manipulating polarized luminescence, offering unprecedented opportunities for next-generation optoelectronic technologies. This review comprehensively examines recent advances in engineering both linearly polarized luminescence (LPL) and circularly polarized luminescence (CPL) from perovskite nanostructures, focusing on structural design principles, chirality transfer mechanisms, and performance optimization strategies. Methods are systematically analyzed to achieve polarized emission, including anisotropic nanocrystal growth, chiral ligand functionalization, and liquid crystal-mediated alignment, while highlighting critical optical factors such as dissymmetry factors and photoluminescence quantum yield. Key challenges in enhancing the precision control over perovskite nanostructures, room-temperature CPL efficiency, and scalable assembly are discussed, with a forward-looking perspective on the integration of artificial intelligence (AI) to accelerate progress in the development of perovskite nanomaterials with customized polarized luminescence. By bridging fundamental insights with technological applications, this review outlines a roadmap for developing perovskite-based polarized light sources that combine high performance, stability, and manufacturability, which are key enablers for the future of quantum photonics, ultra-secure communication, and intelligent optical systems. Show less
To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD). A bidirectional and multivariable Mendelia Show more
To identify the connections between lipid biomarkers and the anti-VEGF therapy response in patients with neovascular age-related macular degeneration (nAMD). A bidirectional and multivariable Mendelian randomization study. The summary statistics for anti-VEGF nAMD treatment response included a total of 128 responders, 51 nonresponders, and 6 908 005 genetic variants available for analysis. The sample size of lipid biomarkers is 441 016 and 12 321 875 genetic variants available for analysis. Two-sample Mendelian randomization (MR) method was conducted to exhaustively appraise the causalities among 13 lipid biomarkers and the risk of different anti-VEGF treatment responses (including visual acuity [VA] and central retinal thickness [CRT]) for nAMD subtypes. Thirteen lipid biomarkers, VA, and CRT. A positive causal relationship was identified between triglycerides (TGs), apolipoproteins (Apos) E2, ApoE3, total cholesterol (TC), and VA response to anti-VEGF therapy in patients with nAMD, as confirmed by MR-Egger, weighted median, and weighted mode models. The MR-Egger model yielded statistically significant results for TC, ApoA-I, ApoB, and ApoA-V in relation to the CRT response to anti-VEGF treatment in patients with nAMD. In the reverse MR, the MR-Egger model identified significant causal relationships between ApoA-I, low-density lipoprotein cholesterol (LDL-c), ApoE3, and ApoF and the VA response. However, this was not the case in the weighted median and weighted mode models. In the MR-Egger model, ApoB, LDL-c, ApoE3, and ApoM were identified as significantly influencing the CRT response. In the multisample MR analysis, TC, high-density lipoprotein cholesterol, LDL-c, and TG were found to be causally related to VA response, and TC was also identified as being causally related to the CRT response to anti-VEGF therapy in patients with nAMD. This MR study suggests unidirectional causality between TG and ApoE3 and the response to anti-VEGF treatment in patients with nAMD. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Show less
Jiaotaiwan (JTW) is a classic traditional Chinese medicine (TCM) prescription for treating depression, but its potential mechanisms are not fully understood. The aim of this study is to detect the lev Show more
Jiaotaiwan (JTW) is a classic traditional Chinese medicine (TCM) prescription for treating depression, but its potential mechanisms are not fully understood. The aim of this study is to detect the levels of serum Short-chain fatty acids (SCFAs) and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP-response element binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway, further revealing the scientific connotation of the antidepressant effect of JTW. In this multicenter, randomized, controlled study, 120 patients with depression were divided into the JTW (16.5 g/d) group, JTW (16.5 g/d) + selective serotonin reuptake inhibitors (SSRIs) group, and SSRIs group. Hamilton depression Scale-24 (HAMD-24) and Self-rating depression scale (SDS) were used for efficacy evaluation. Enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR) were used to evaluate the expression levels of cAMP-PKA-CREB-BDNF signaling pathway. Serum SCFAs concentrations were analyzed using liquid chromatograph-mass spectrometer (LC-MS) targeted metabolomics. After eight weeks of treatment, HAMD score and SDS score were significantly decreased in the three groups, and HAMD score in JTW + SSRIs group was significantly lower than that in SSRIs group. After treatment, the expression levels of cAMP-PKA-CREB-BDNF signaling pathway were significantly increased in the three group, with the JTW + SSRIs group showing more significant increase. After treatment, the levels of isobutyric, butyric, isovaleric, and valeric acids in the JTW + SSRIs groups were significantly higher than that before treatment, and the levels of isobutyric, and isovaleric acids in the JTW + SSRIs group was significantly higher than that in the JTW group and SSRIs groups. JTW can alleviate symptoms in patients with depression, and its antidepressant mechanism may be related to regulating serum SCFAs and cAMP-PKA-CREB-BDNF signaling pathway. Show less
Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagi Show more
Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagic pathway has emerged as an avenue for cancer therapy. In the present study, we identify apolipoprotein B100 (ApoB100), a key modulator of lipid metabolism, as a potential prognostic biomarker of ovarian cancer. ApoB100 functioned as a tumor suppressor in ovarian cancer, and the knockdown of ApoB100 promoted ovarian cancer progression in vivo. Moreover, ApoB100 blocked autophagic flux, which was dependent on interfering with the lipid accumulation/endoplasmic reticulum (ER) stress axis. The effects of LFG-500, a novel synthetic flavonoid, on ApoB100 induction were confirmed using proteomics and lipidomics analyses. Herein, LFG-500 induced lipid accumulation and ER stress and subsequently blocked autophagy by upregulating ApoB100. Moreover, data from in vivo experiments further demonstrated that ApoB100, as well as the induction of the lipid/ER stress axis and subsequent blockade of autophagy, were responsible for the anti-tumor effects of LFG-500 on ovarian cancer. Hence, our findings support that ApoB100 is a feasible target of ovarian cancer associated with lipid-regulated autophagy and provide evidence for using LFG-500 for ovarian cancer treatment. Show less
Increasing evidence underscores the driving role of coding and non-coding variants in cancer development. Analyzing gene sets in biological processes offers deeper insights into the molecular mechanis Show more
Increasing evidence underscores the driving role of coding and non-coding variants in cancer development. Analyzing gene sets in biological processes offers deeper insights into the molecular mechanisms of carcinogenesis. Here, we developed geMER to identify candidate driver genes genome-wide by detecting mutation enrichment regions within coding and non-coding elements. We subsequently designed a pipeline to identify a core driver gene set (CDGS) that broadly promotes carcinogenesis across multiple cancers. CDGS comprising 25 genes for 25 cancers displayed instability in DNA aberrations. Variants within the TTN enrichment region may influence the folding of the I-set domain by altering local polarity or side-chain chemistry properties of amino acids, potentially disrupting its antigen-binding capacity in LUAD. Multi-omics analysis revealed that APOB emerged as a candidate oncogene in LIHC, whose genetic alterations within the enrichment region may activate key TFs, upregulate DNA methylation levels, modulate critical histone modifications, and enhance transcriptional activity in the HepG2 and A549 cell lines compared to Panc1. Additionally, CDGS mutation status was an independent prognostic factor for the pan-cancer cohort. High-risk patients tended to develop an immunosuppressive microenvironment and demonstrated a higher likelihood of responding to ICI therapy. Finally, we provided a user-friendly web interface to explore candidate driver genes using geMER ( http://bio-bigdata.hrbmu.edu.cn/geMER/ ). Show less
Sperm flagellum defects are tightly associated with male infertility. Centriolar satellites are small multiprotein complexes that recruit satellite proteins to the centrosome and play an essential rol Show more
Sperm flagellum defects are tightly associated with male infertility. Centriolar satellites are small multiprotein complexes that recruit satellite proteins to the centrosome and play an essential role in sperm flagellum biogenesis, but the precise mechanisms underlying this role remain unclear. Show less
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. W Show more
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 Show less
Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treat Show more
Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation. Show less
The Kruppel-like factor 15(KLF15) gene functions as a crucial transcriptional modulator involved in numerous cellular processes such as differentiation, proliferation, growth, and programmed cell deat Show more
The Kruppel-like factor 15(KLF15) gene functions as a crucial transcriptional modulator involved in numerous cellular processes such as differentiation, proliferation, growth, and programmed cell death. The epithelial-to-mesenchymal transition (EMT) provides malignant cells with the adaptability and movement necessary for tumor advancement and spread, with zinc finger E-box binding homeobox 1(ZEB1) playing a pivotal role as a transcriptional factor in EMT. This investigation initially examined the association between the KLF15 protein and EMT associated transcription factors such as ZEB1, Slug, and Snail, along with marker proteins like E-cadherin and β-catenin in bladder cancer. Furthermore, we explored their connections with clinicopathological attributes and conducted prognostic analyses. Immunohistochemical techniques were utilized to ascertain the presence of KLF15 protein and EMT-associated transcription factor proteins, along with their marker proteins in 110 specimens of bladder cancer tissues. Concurrently, clinicopathological data and postoperative survival statistics were amassed. The rates of KLF15 and Slug protein expression were linked with pathological differentiation, lymphatic involvement, and pTNM staging. The protein expression rates of ZEB1, Slug, Snail, E-cadherin, and β-catenin also showed associations with lymphatic metastasis and pTNM stages. Notably, the expression of KLF15, the coexpression of KLF15 and ZEB1, and lymphatic metastasis emerged as independent prognostic indicators for the overall survival rates in bladder cancer cases. EMT enhances the risk of tumor recurrence and reduces overall survival durations in bladder cancer cases. Furthermore, KLF15 is a significant contributor to the EMT pathway in bladder cancer, primarily through its interaction with the transcription factor ZEB1. KLF15 and ZEB1 might serve as key biomarkers for metastasis and prognosis, offering potential new targets for therapeutic intervention in bladder cancer. Show less
Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emergi Show more
Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emerging evidence has identified significant associations between CAVS and key biomarkers, including Lp(a) (lipoprotein [a]), low-density lipoprotein cholesterol, and PCSK9 (proprotein convertase subtilisin/kexin type 9). However, robust evidence from randomized controlled trials is still lacking to substantiate these associations. The EPISODE (Effect of PCSK9 Inhibitors on Calcific Aortic Valve Stenosis) trial is a prospective, evaluator-blinded, randomized controlled trial designed to assess the therapeutic efficacy of PCSK9 inhibitors in patients with CAVS. A total of 160 patients with mild-to-moderate or asymptomatic severe CAVS will be randomly assigned to receive either statin monotherapy or a combination of statins and PCSK9 inhibitors. Participants will undergo follow-up assessments at 3-month intervals for 24 months, including transthoracic ultrasonic cardiogram, computed tomography, and quality-of-life evaluations using the EuroQol-5 Dimension-3 Level questionnaire. The primary end point is the annualized change in peak aortic jet velocity, whereas secondary end points encompass changes in aortic valve area, calcification score, incidence of heart valve surgery, and quality of life. Safety end points include all-cause mortality and cardiovascular events. The trial aims to evaluate the efficacy of PCSK9 inhibitors in modulating disease progression, reducing adverse cardiovascular events, and improving clinical outcomes in patients with CAVS. The anticipated findings are expected to provide critical insights for developing novel therapeutic strategies for early intervention in CAVS. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04968509. Show less
Cang Li · 2025 · Bulletin of experimental biology and medicine · Springer · added 2026-04-24
The paper is aimed to screen the target molecules of miR-12 and to further explore the mechanism of GAS5 action in prostate cancer. The expression of GPRC5B in prostate cancer cell lines LNCaP, VCaP, Show more
The paper is aimed to screen the target molecules of miR-12 and to further explore the mechanism of GAS5 action in prostate cancer. The expression of GPRC5B in prostate cancer cell lines LNCaP, VCaP, 22RV1, DU145, and PC3 was measured by quantitative real-time PCR with reverse transcription (RT-qPCR) and variations in GPRC5B expression were analyzed after down-regulating GAS5 or silencing miR-12. CCK8 and plate clone experiments were performed to detect changes in proliferative activity and colony-forming capacity of prostate cancer cells after down-regulating GPRC5B. After transfection of prostate cancer cells with sh-GAS5 and/or miR-12 inhibitor, the changes in GPRC5B expression were evaluated with RT-qPCR and Western blotting. Our results showed that GPRC5B was highly expressed in prostate cancer cell lines. Down-regulating of GAS5 decreased GPRC5B expression, while silencing miR-12 increased it. CCK8 and plate clone experiments showed that expression of GPRC5B increased proliferative activity and clone formation ability of prostate cancer cells. RT-qPCR and Western blotting revealed that miR-12 inhibited the promoting effect of GAS5 on GPRC5B expression. Thus, GPRC5B is directly bound to miR-12. GAS5 promotes proliferation, migration, and invasion of prostate cancer cells and participates in malignant progression of tumors by suppressing miR-12-mediated regulation of GPRC5B expression. Show less
This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from u Show more
This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from up to 12 weeks were analyzed to assess the effects of tafolecimab 450 mg every four weeks (Q4W) in patients with T2D and hypercholesterolemia. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Secondary endpoints included the proportion of participants achieving LDL-C levels below 1.8 mmol/L at weeks 12, the proportion of patients achieving LDL-C ≥ 50% reduction and LDL-C < 1.4 mmol/L, as well as percentage changes from baseline to week 12 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and triglyceride (TG) levels. The reduction in LDL-C from baseline was significantly greater in patients receiving tafolecimab than in those receiving placebo (estimated treatment difference: - 64.02%, 95% confidence interval: [- 68.08%, - 59.96%], P < 0.0001). The proportion of patients achieving a reduction of over 50% and an absolute LDL-C value below 1.4 mmol/L was significantly higher in the tafolecimab group than that in the placebo group (P < 0.0001). Furthermore, a significantly greater proportion of patients in the tafolecimab group achieved LDL-C levels below 1.8 mmol/L at week 12 compared to the placebo group (P < 0.0001). The tafolecimab group also showed significant reductions in TG, non-HDL-C, apo B, and Lp(a) from baseline to week 12 compared to the placebo group (all P < 0.001). The incidence of adverse events was generally similar between the two groups. Tafolecimab 450 mg Q4W demonstrated a superior lipid-lowering efficacy and favorable safety profile compared to placebo. This suggests it could be a promising new treatment option for Chinese patients with T2D and hypercholesterolemia. Show less
Diabetic retinopathy (DR) is a common complication of type II diabetes mellitus (T2DM) and a leading cause of blindness in the working population. Apolipoprotein levels have been reported to be associ Show more
Diabetic retinopathy (DR) is a common complication of type II diabetes mellitus (T2DM) and a leading cause of blindness in the working population. Apolipoprotein levels have been reported to be associated with the risk of DR. This study aimed to develop a predictive model for DR based on apolipoproteins (apoA and apoB) and menopausal status in Chinese Han women with T2DM and to evaluate the model's effectiveness. Data from 2339 T2DM women were collected between January 2018 and June 2022. Multilevel regression was used to explore the independent effect of apolipoproteins and interaction between apolipoproteins and menopausal status on DR and proliferative diabetic retinopathy (PDR). Receiver operating characteristic (ROC) analysis was performed to compare the fitting degree and predictive efficiency of different models. Results showed that both apoA and apoB were independent influencing factors for DR and PDR and interacted significantly with menopausal status. The interaction between apoA and menopausal status had a protective effect on DR [OR (95% CI) = 0.925 (0.858-0.996), P = 0.040] and PDR [OR (95% CI) = 0.937 (0.895-0.981), P = 0.006]. In contrast, the interaction between apoB and menopausal status was a risk factor for DR [OR (95% CI) = 1.684 (1.141-2.379), P = 0.008)] and PDR [OR (95% CI) = 3.377 (1.148-9.937), P = 0.027]. ROC analysis demonstrated that the interaction model outperformed models without interaction terms (P < 0.01). The area under the curve for the interaction model was 0.879 (95% CI 0.864-0.893) for DR and 0.930 (95% CI 0.915-0.945) for PDR. These findings suggest that the interaction model is highly efficient in predicting DR, particularly PDR, in Chinese Han women with T2DM. Show less
This study aims to identify and characterize daily activity accumulation patterns (bouts of physical activity and sedentary behavior) among adolescents and then to explore the associations between the Show more
This study aims to identify and characterize daily activity accumulation patterns (bouts of physical activity and sedentary behavior) among adolescents and then to explore the associations between these groups and depressive symptoms. A total of 521 adolescents aged 13-18 years from Wuhan and Changsha, China, were included. Bouts of physical activity (PA) and sedentary behavior (SED) were measured using accelerometers. The Center for Epidemiologic Studies Depression Scale was used to assess participants' depressive symptoms. Latent profile analysis was employed to identify distinct groups based on their activity patterns. Three distinct groups were identified: "Prolonged sitters" ( The synergistic effect of strategies to reduce total SED duration by limiting SED bouts to 30 min or less and increasing light physical activity (LPA) may also be effective in alleviating depressive symptoms in adolescents. Show less
Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is Show more
Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure. Conversely, Hey2 depletion in adult mouse hearts and zebrafish enhances the expression of mitochondrial oxidation genes and cardiac function. Multifaceted genome-wide analyses reveal that HEY2 enriches at the promoters of genes known to regulate metabolism (including Ppargc1, Esrra and Cpt1) and colocalizes with HDAC1 to effectuate histone deacetylation and transcriptional repression. Consequently, restoration of PPARGC1A/ESRRA in Hey2- overexpressing zebrafish hearts or human cardiomyocyte-like cells rescues deficits in mitochondrial bioenergetics. Knockdown of Hey2 in adult mouse hearts protects against doxorubicin-induced cardiac dysfunction. These studies reveal an evolutionarily conserved HEY2/HDAC1-Ppargc1/Cpt transcriptional module that controls energy metabolism to preserve cardiac function. Show less
To investigate the clinical and pathological characteristics of patients with non-small cell lung cancer exhibiting coexistence of Clinical data, as well as histopathological, immunohistochemical, and Show more
To investigate the clinical and pathological characteristics of patients with non-small cell lung cancer exhibiting coexistence of Clinical data, as well as histopathological, immunohistochemical, and molecular pathological characteristics, of two patients harboring both Both patients were women aged 57 and 66 years. The two cases were diagnosed as invasive lung adenocarcinoma, and immunohistochemical staining showed that all tumor cells expressed CK7, Napsin A, TTF-1, and PD-L1. In Case 1, an Show less
Studies showed that contaminants adhered to the surface of nano-polystyrene microplastics (NPs) have a toxicological effect. Juveniles tilapia were dispersed into four groups: the control group A, 75 Show more
Studies showed that contaminants adhered to the surface of nano-polystyrene microplastics (NPs) have a toxicological effect. Juveniles tilapia were dispersed into four groups: the control group A, 75 nm NPs exposed group B, 5 ng·L Show less
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Show more
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Fritillariae Thunbergii Bulbus, Leonuri Herba, and Forsythiae Fructus, has shown efficacy in treating cardiovascular diseases, although its mechanisms are unclear. This study aimed to explore the protective effects of QRSJF against atherosclerosis and the mechanisms involved. The composition of QRSJF was analyzed using Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. An 8-week high-fat diet (HFD)-induced atherosclerosis model was established in ApoE Both low- and high-dose QRSJF effectively attenuated dyslipidemia and decreased serum inflammatory cytokine levels in HFD-fed ApoE QRSJF improves dyslipidemia and reduces atherosclerotic plaque in ApoE Show less
BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by pathogenesis involving numerous factors. Recent research has highlighted the significant role of autoimmunity in the Show more
BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder characterized by pathogenesis involving numerous factors. Recent research has highlighted the significant role of autoimmunity in the initiation and progression of AD, with autoantibodies emerging as a pivotal area of investigation. Nevertheless, the influence of autoantibodies in AD is marked by substantial heterogeneity, they may either mitigate disease progression by clearing pathogenic protein aggregates or exacerbate the pathological process through mechanisms such as the activation of inflammatory responses or the induction of neuronal damage.ObjectiveThis review aims to synthesize the various roles of autoantibodies in AD, examine the factors that influence their functions, and assess their potential application in precision immunotherapy.MethodsPubMed and Web of Science databases were searched for English-language papers (2015-2025). Peer-reviewed human, animal and cell studies, systematic reviews and meta-analyses were screened independently by two reviewers.ResultsA total of 87 studies were selected for inclusion, spanning human, animal, and cellular research. The findings indicated that certain autoantibodies, such as those targeting amyloid-β, tau, or 4-hydroxynonenal, may confer neuroprotective effects. Conversely, other autoantibodies, including those against BACE1, aquaporin-4, or HuD, may exacerbate AD pathology. Importantly, some autoantibodies were found to exhibit dual roles, contingent upon their specific modifications or the context of the disease.ConclusionsAutoantibodies constitute a double-edged immune axis in AD. Their impact hinges on antigen class, disease stage, isotype affinity and glycosylation. Precision strategies-like CAAR-T cell therapy, glycosylation modulation, and affinity optimization-offer therapeutic promise but require further validation. Show less
Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored. Hence, Show more
Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored. Hence, exploring the function and regulatory mechanisms of Slug is critical for the treatment of CRC. Protein expressions of Slug, N-cadherin, E-cadherin, Snail, HIF-1α, SUMO- 1, Drp1, Opa1, Mfn1/2, PGC-1α, NRF1, and TFAM were measured through western blot. To evaluate the protein expression of Slug and SUMO-1, an immunofluorescence assay was used. Cell migration ability was tested through transwell assay. The SUMOylation of Slug was examined through CO-IP assay. Slug displayed higher expression and facilitated tumor metastasis in CRC. In addition, hypoxia treatment was discovered to upregulate HIF-1α, Slug, and SUMO-1 levels, as well as induce Slug SUMOylation. Slug SUMOylation markedly affected mitochondrial biosynthesis, fusion, and mitogen-related protein expression levels to trigger mitochondrial stress. Additionally, the induced mitochondrial stress by hypoxia could be rescued by Slug inhibition and TAK-981 treatment. Our study expounded that hypoxia affects mitochondrial stress and facilitates tumor metastasis of CRC through Slug SUMOylation. Show less