Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathologic Show more
Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression. Chronic mannose overload increases β-amyloid (Aβ) burdens and exacerbates cognitive impairments, which are reversed by a mannose-free diet or mannose transporter antagonists. Mechanistically, single-cell RNA sequencing and metabolomics suggested that mannose-mediated N-glycosylation of BACE1 and Nicastrin enhances their protein stability, promoting Aβ production. Additionally, reduced mannose intake decreased BACE1 and Nicastrin stability, ultimately lowering Aβ production and mitigating AD pathology. this results highlight that high-dose mannose consumption may exacerbate AD pathogenesis. Restricting dietary mannose may have therapeutic benefits. Show less
Hyperlipidemia and its associated hepatic steatosis pose significant global health burdens, necessitating novel therapeutic strategies. High-fat diet (HFD)-fed C57BL/6 mice received TAC (2.5, 5.0, 10. Show more
Hyperlipidemia and its associated hepatic steatosis pose significant global health burdens, necessitating novel therapeutic strategies. High-fat diet (HFD)-fed C57BL/6 mice received TAC (2.5, 5.0, 10.0 g/L) or simvastatin for 2 weeks. Metabolic parameters, serum lipid profiles, hepatic function markers, and histopathology were systematically analyzed. Molecular pathways were interrogated through qPCR, Western blot, and pharmacological inhibition of AMPK (Compound C) and PPARα (GW6471). TAC treatment demonstrated significant dose-dependent improvements across multiple parameters. Compared to HFD controls, TAC reduced body weight by 21.3% and liver index by 18.7%, while lowering fasting blood glucose levels by 32.4%. Serum analyses showed substantial reductions in total cholesterol (46.2%), triglycerides (38.5%), and LDL-cholesterol (52.1%), accompanied by a 29.8% increase in HDL-cholesterol. Hepatic function improved markedly, with ALT and AST levels decreasing by 57.3% and 49.6% respectively. Histopathological examination revealed a 68.4% reduction in hepatic lipid accumulation. At the molecular level, TAC treatment resulted in a 2.7-fold increase in AMPK phosphorylation while significantly reducing HMGCR expression by 63.1% and nuclear SREBP-1c levels by 71.5%. Concurrently, TAC upregulated PPARα and LXRα expression by 3.1-fold and 2.4-fold respectively, leading to enhanced expression of lipolytic enzymes LPL and HL by 2.8-fold and 2.1-fold. These beneficial effects were completely abolished by co-treatment with pathway-specific inhibitors. TAC ameliorates hyperlipidemia and hepatic steatosis through dual modulation of AMPK/SREBP-1c-mediated lipid synthesis and PPARα/LXRα-driven lipolysis, presenting a multifaceted therapeutic approach for metabolic disorders. Show less
Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy, yet this practice often induces hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous Show more
Intensive aquaculture frequently utilizes high-fat diets (HF) as a cost-effective strategy, yet this practice often induces hepatic steatosis, oxidative stress, and chronic inflammation in carnivorous fish. Betaine, a natural methyl donor, has shown potential as a functional feed additive, but its comprehensive protective mechanisms under HF stress remain to be fully elucidated. Juvenile largemouth bass (Micropterus salmoides) were fed one of four isonitrogenous diets for 8 weeks: a normal-fat control (Control), a high-fat diet (HF), and two high-fat diets supplemented with 0.5% (HFB0.5) or 1.0% (HFB1) betaine. Growth performance, digestive enzyme activities, serum biochemical parameters, hepatic antioxidant capacity, and the expression of genes related to antioxidant defense, lipid metabolism, and inflammation were analyzed. The HF group exhibited significantly impaired growth, digestive function, and antioxidant capacity, along with elevated lipid peroxidation, dyslipidemia, and pro-inflammatory cytokine expression. Betaine supplementation restored growth performance and feed efficiency to control levels, ameliorated digestive enzyme activities (particularly enhancing lipase), and activated the hepatic Nrf2-Keap1 pathway, upregulating antioxidant genes (nrf2, sod1, cat, gpx, ho-1, gr) and enhancing enzyme activities. Betaine also improved serum lipid profiles, upregulated genes related to fatty acid oxidation (pparα, cpt-1) and lipolysis (lpl, hsl), suppressed lipogenic genes (srebp-1, fas), and rebalanced inflammatory cytokines by reducing tnf-α and il-1β while increasing tgf-β1 and il-10. Dietary betaine effectively counteracts HF-induced metabolic stress in M. salmoides through coordinated multi-pathway regulation. It enhances antioxidant defense, reprograms hepatic lipid metabolism toward catabolism, and restores inflammatory homeostasis. These findings underscore betaine's role as a multi-functional feed additive capable of mitigating HF-related metabolic disorders and promoting overall health in carnivorous fish aquaculture. Show less
Central nervous system (CNS) tumors often harbor alterations in genes regulating key cellular pathways, including fibroblast growth factor receptor (FGFR) genes. Here, we report the efficacy and safet Show more
Central nervous system (CNS) tumors often harbor alterations in genes regulating key cellular pathways, including fibroblast growth factor receptor (FGFR) genes. Here, we report the efficacy and safety of treatment with pemigatinib, an oral, potent, selective FGFR1-3 inhibitor, in patients with advanced FGFR-altered CNS tumors. FIGHT-207 was a single-arm, open-label, phase 2 study of pemigatinib in patients with advanced solid tumors harboring FGFR fusions/rearrangements or other mutations. Patients received pemigatinib 13.5 mg once daily until disease progression or unacceptable toxicity. Endpoints included tumor response and safety. Of the 13 patients with CNS tumors in FIGHT-207, 10 had glioblastoma. Fibroblast growth factor receptor alterations were FGFR3-TACC3 fusions (n = 9), FGFR1 K656E mutations (n = 2), FGFR1 N546K mutation (n = 1), and FGFR1-MITF fusion (n = 1). Three patients (23%) displayed objective responses (1 complete, 2 partial). Safety was consistent with the overall FIGHT-207 population. Pemigatinib had antitumor activity and a manageable safety profile in patients with CNS tumors. Show less
Radiation-induced brain injury (RIBI) is a significant complication following radiotherapy for brain tumors, leading to neurocognitive deficits and other neurological impairments. This study aims to i Show more
Radiation-induced brain injury (RIBI) is a significant complication following radiotherapy for brain tumors, leading to neurocognitive deficits and other neurological impairments. This study aims to identify potential biomarkers and therapeutic targets for RIBI by utilizing advanced proteomic techniques to explore the molecular mechanisms underlying RIBI. A rat model of RIBI was established and subjected to whole-brain irradiation (30 Gy). Tandem mass tagging (TMT)-based quantitative proteomics, combined with high-resolution mass spectrometry, was used to identify differentially expressed proteins (DEPs) in the brain tissues of irradiated rats. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to identify the biological processes and pathways involved. Protein-protein interaction (PPI) networks were constructed to identify key hub proteins. A total of 35 DEPs were identified, including PHLDA3, APOE and CPE. GO enrichment analysis revealed that the DEPs were mainly involved in lipid transport, cell adhesion, and metabolic processes. KEGG analysis highlighted the enrichment of pathways related to metabolism, tight junctions, and PPAR signaling. APOE was identified as a key hub protein through PPI network analysis, indicating its potential role in RIBI pathophysiology. Immunohistochemistry further validated the increased expression of PHLDA3, APOE, and CPE in the brain tissue of irradiated rats. This study provides valuable insights into the molecular mechanisms of RIBI by identifying key proteins and their associated pathways. The findings suggest that these proteins, particularly APOE and PHLDA3, could serve as potential biomarkers and therapeutic targets for clinical intervention in RIBI. These results not only enhance our understanding of RIBI's molecular pathology but also open new avenues for the development of targeted therapies to mitigate radiation-induced neurotoxicity. Show less
Ruotong Li, Wenye Zhao, Jiaxin Zhang+7 more · 2025 · FASEB journal : official publication of the Federation of American Societies for Experimental Biology · added 2026-04-24
The global increase in muscle weakness poses a critical public health concern. Nutritional interventions that improve muscular function hold promise as a therapeutic potential. Vitamin A (VA) and its Show more
The global increase in muscle weakness poses a critical public health concern. Nutritional interventions that improve muscular function hold promise as a therapeutic potential. Vitamin A (VA) and its active metabolites have been implicated in muscle development and the transformation of muscle fiber types. However, conventional VA formulations are restricted by poor stability and low bioavailability. In this study, a stable Nano VA was utilized to systematically evaluate its effects on muscle development and exercise performance in mice, as well as to explore its underlying mechanisms. A total of 44 male C57BL/6J mice were randomly divided into four groups: (i) normal control (NC), (ii) 5 mg/kg Nano VA (5 NVA), (iii) 10 mg/kg Nano VA (10 NVA), and (iv) 10 mg/kg VA (10 VA). The 10 NVA group demonstrated significantly improved muscle strength and swimming endurance, compared with the NC group. Further examination suggested a significant increase in myofiber diameter, cross-sectional area, and the content of fast-twitch fibers. Additionally, Nano VA treatment improved glucose tolerance and insulin sensitivity. To elucidate the mechanism by which Nano VA enhances muscle locomotor ability, transcriptomics and metabolomics data identified 111 differentially expressed genes and 253 differential metabolites. Of these, Angptl4, Ppp1r3a, and Cyp26b1 were identified as candidate regulators of muscle development and myofiber type transformation. In conclusion, Nano VA regulates muscle development and promotes muscle fiber type conversion, thus improving muscle strength and endurance in mice. Moreover, Nano VA facilitates mitigating and improving myasthenia gravis-related conditions. Show less
Gentidelasides A-G (1-7) seven unreported loganin derivatives and fourteen known compounds (8-21) were isolated from the flowers of Gentiana delavayi Franch. Their structures including absolute config Show more
Gentidelasides A-G (1-7) seven unreported loganin derivatives and fourteen known compounds (8-21) were isolated from the flowers of Gentiana delavayi Franch. Their structures including absolute configurations were unambiguously elucidated by analysis of extensive NMR spectroscopy, ECD, and HRESIMS, as well as enzymatic hydrolysis. In vitro bioassay, compound 7 showed obvious inhibitory effects on the production of Aβ40 and Aβ42, with IC Show less
Xiaolei Song, Chenchen Wang, Qin Ding+8 more · 2025 · Journal of controlled release : official journal of the Controlled Release Society · Elsevier · added 2026-04-24
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. The vicious circle between amyloid-β peptide (Aβ) overgeneration and microglial dysfunction is an important path Show more
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. The vicious circle between amyloid-β peptide (Aβ) overgeneration and microglial dysfunction is an important pathological event that promotes AD progression. However, therapeutic strategies toward only Aβ or microglial modulation still have many problems. Herein, inspired by the Aβ transportation, an Aβ-derived peptide (CKLVFFAED) engineered biomimetic nanodelivery system (MK@PC-R NPs) is reported for realizing BBB penetration and reprogram neuron and microglia in AD lesion sites. This hollow mesoporous Prussian blue-based MK@PC-R NPs carrying curcumin and miRNA-124 can down-regulate β secretase expression, thereby inhibiting Aβ production and reducing Aβ-induced neurotoxicity. Meanwhile, MK@PC-R NPs with excellent antioxidant and anti-inflammatory properties could normalize the microglial phenotype and promote Aβ degradation, providing neuroprotection. As expected, after treatment with MK@PC-R NPs, the Aβ burdens, neuron damages, neuroinflammation, and memory deficits of transgenic AD mice (APP/PS1 mice) are significantly attenuated. Overall, this biomimetic nanodelivery system with anti-Aβ and anti-inflammatory properties provides a promising strategy for the multi-target therapy of early AD. Show less
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompl Show more
Impaired glucose-stimulated insulin secretion (GSIS) is a hallmark of β cell dysfunction in diabetes. Epigenetic mechanisms govern cellular glucose sensing and GSIS by β cells, but they remain incompletely defined. Here, we found that BAF60a functions as a chromatin regulator that sustains biphasic GSIS and preserves β cell function under metabolic stress conditions. BAF60a was downregulated in β cells from obese and diabetic mice, monkeys, and humans. β cell-specific inactivation of BAF60a in adult mice impaired GSIS, leading to hyperglycemia and glucose intolerance. Conversely, restoring BAF60a expression improved β cell function and systemic glucose homeostasis. Mechanistically, BAF60a physically interacted with Nkx6.1 to selectively modulate chromatin accessibility and transcriptional activity of target genes critical for GSIS coupling in islet β cells. A BAF60a V278M mutation associated with decreased β cell GSIS function was identified in human donors. Mice carrying this mutation, which disrupted the interaction between BAF60a and Nkx6.1, displayed β cell dysfunction and impaired glucose homeostasis. In addition, GLP-1R and GIPR expression was significantly reduced in BAF60a-deficient islets, attenuating the insulinotropic effect of GLP-1R agonists. Together, these findings support a role for BAF60a as a component of the epigenetic machinery that shapes the chromatin landscape in β cells critical for glucose sensing and insulin secretion. Show less
Biomolecular condensates, membrane-less assemblies formed by phase separation, are implicated in neurodegenerative disease, but their role in Alzheimer's disease (AD) remains unclear. Here, we report Show more
Biomolecular condensates, membrane-less assemblies formed by phase separation, are implicated in neurodegenerative disease, but their role in Alzheimer's disease (AD) remains unclear. Here, we report that in the brain of AD patients and animal models, an elevation of poly(C)-binding protein 2 (PCBP2) correlates with biomolecular condensation that involves phase separation. These condensates sequester large numbers of mitochondrial and mRNA-binding proteins, leading to the outside impairment of mitochondrial morphology and function, and BACE1 mRNA decay relative to amyloid deposition. We then identify a small molecule CN-0928 that inhibits the condensates by reducing PCBP2 protein level and mitigates AD pathology and cognitive decline, in which CN-0928 binding to a target protein integrator complex subunit 1 (INTS1) allows to regulate PCBP2 expression. Our findings place PCBP2 condensates as a key player that cooperates the seemingly disparate but important pathways, and show pharmacological modulation of PCBP2 as an effective approach for treating AD. Show less
The Huainan pig (HN) is known for its impressive litter size and exquisite meat quality. However, it also exhibits certain drawbacks such as excessive fat deposition, a relatively low percentage of le Show more
The Huainan pig (HN) is known for its impressive litter size and exquisite meat quality. However, it also exhibits certain drawbacks such as excessive fat deposition, a relatively low percentage of lean meat percentage, and a slower growth rate. Crossbreeding with lean-type breeds, such as Large White, Landrace, and Berkshire can enhance offspring traits, and increase genetic diversity. In this study we employed RNA-seq technology to identify differentially expressed genes (DEGs) in subcutaneous adipose tissue (SAT) samples from HN pigs and their crosses with multiple breeds (with three replicates per group). In the SAT of Huainan × Berkshire pigs (BH), Huainan × Yorkshire pigs (YH), and Huainan × Landrace pigs (LH), numerous key functional genes were identified, including In conclusion, these findings offer valuable insights and provide a foundation for future research on the molecular mechanisms underlying fat deposition in pigs. Show less
Recent researches highlight the interdependence of lipoprotein(a) [Lp(a)] and Lp(a)-associated cardiovascular risk with the background inflammatory burden. This study aimed to investigate whether syst Show more
Recent researches highlight the interdependence of lipoprotein(a) [Lp(a)] and Lp(a)-associated cardiovascular risk with the background inflammatory burden. This study aimed to investigate whether systemic inflammation modulates Lp(a)-associated coronary stenosis in chronic coronary syndromes (CCS). A total of 1513 participants undergoing angiography at a tertiary cardiology center in China were included in our retrospective, cross-sectional study. Participants were categorized into normal, mild, and severe groups based on the Gensini Scores, which quantitatively assess stenosis severity. Multinomial logistic models were calculated according to accompanying systemic inflammation concentration. Participants with elevated Lp(a) levels had a high coronary stenosis risk: fully adjusted model odds ratios (ORs) [95% confidence intervals (CIs)] for the mild vs. normal and severe vs. normal groups were 1.47 (1.11-1.96) and 1.68 (1.21-2.33). Notably, the strongest Lp(a)-coronary stenosis associations after multi-variable adjustment persisted only in low inflammation concentration [systemic inflammation response index (SIRI) < 0.64)] [mild vs. normal, OR 2.03, 95% CI 1.17-3.54, Elevated Lp(a) correlates with coronary stenosis only in low inflammation concentration. Considering systemic inflammation in personalized Lp(a)-lowering therapies is more conducive for CCS managements. Show less
Symptom burden in primary brain tumor patients varies, emphasizing the need for comprehensive understanding to improve patient care. This study aims to identify distinct symptom clusters among brain t Show more
Symptom burden in primary brain tumor patients varies, emphasizing the need for comprehensive understanding to improve patient care. This study aims to identify distinct symptom clusters among brain tumor patients in Shanghai, China, using Latent Profile Analysis (LPA) to guide personalized diagnosis, treatment, and supportive care. A longitudinal study was conducted among 161 patients with primary brain tumors in Shanghai. Participants completed the MD Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) at three intervals: the day of admission (T1), three days after surgery (T2), and two weeks after surgery (T3). Latent Profile Analysis (LPA) was used to identify subgroups with unique symptom patterns. Six distinct subgroups were identified (entropy = 0.964), ranging from low-burden to persistently severe patterns. Subgroup membership was partially associated with age, tumor grade, and diagnosis. These subgroups were: transient postoperative burden group, stable symptom with cognitive emergence group, distress-predominant, low burden group, elderly-high grade, persistently severe group, nausea-dominant recovery group, and distress-plus-nausea, younger urban group. Our findings reveal substantial heterogeneity in perioperative symptom experiences among brain tumor patients. Identifying subgroups with high and persistent symptom burden may help clinicians target interventions such as enhanced education, proactive monitoring, rehabilitation, psychological support, and antiemetic management. This subgroup-based approach may improve quality of life, reduce morbidity, and guide precision supportive care in neuro-oncology. Show less
Lipid metabolism abnormalities and inflammation have been implicated in gallstone disease (GSD) development, but the causal relationships and potential mediation effects among lipid metabolites, infla Show more
Lipid metabolism abnormalities and inflammation have been implicated in gallstone disease (GSD) development, but the causal relationships and potential mediation effects among lipid metabolites, inflammatory factors, and GSD remain unclear. The aim of this study is to explore the causal relationships among these 3 factors. This study employed 2-sample Mendelian Randomization (TSMR) and 2-step MR to investigate the causal relationships and potential mediation effects among 91 inflammatory factors, 6 lipid metabolism-related molecules (HDL-C, LDL-C, TG, total cholesterol, ApoA1, and ApoB), and GSD. We opted for 4 distinct MR analysis methods including inverse variance weighted method, weighted median method, MR-Egger regression method and MR-PRESSO analysis. Sensitivity analyses included MR-Egger intercept tests, Cochran's Q statistic, Steiger tests, and leave-one-out analyses. Product of coefficients method was used to estimate mediation proportion. TSMR analysis revealed that every 1-unit increase in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), the risk of GSD decreased by 16.5%, 10.2%, 8.4%, and 13.1%, respectively. Inflammatory factors such as Natural killer cell receptor 2B4 (CD244), Macrophage colony-stimulating factor 1 (CSF-1), and interleukin-18 receptor 1 (IL-18R1) were identified as risk factors for GSD, while Fibroblast growth factor 19 levels (FGF19), Interleukin-1-alpha levels (IL-1α), and Interleukin-8 levels (IL-8) were found to be protective. Mediation analysis through 2-step MR identified potential pathways involving ApoA1--IL-8--GSD (P = .084) and IL-1α--ApoB--GSD (P = .117). This study provides robust evidence of causal links between specific lipid metabolites and GSD, as well as suggestive causal associations for several inflammatory factors. However, mediation analysis did not support significant roles for lipids or inflammatory factors as mediators in GSD pathogenesis. Future research could be further pursued in areas such as drug target intervention and mechanistic studies. Show less
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular bacterial pathogen that grows within a specialized membrane-bound compartment known as the Salmonella-containing Show more
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a facultative intracellular bacterial pathogen that grows within a specialized membrane-bound compartment known as the Salmonella-containing vacuole (SCV). The molecular composition and regulatory mechanisms governing SCV dynamics remain incompletely understood. In this study, we employed proximity-dependent biotin identification (BioID) to analyze the SCV proteome during infection. For this, we targeted the UltraID biotin ligase to the SCV by fusing it to a type 3 secreted effector. We demonstrate that the bacteria express and translocate the effector-UltraID fusion protein directly into host cells for labeling of the cytosolic face of the SCV surface. Proteomic analysis of biotinylated proteins revealed previously undescribed proteins associated with the SCV, including regulators of vesicular trafficking, cellular metabolism and lipid transport. Among these, VPS13C, a lipid transporter and membrane contact site protein, was identified as a critical regulator of SCV morphology and fission. Functional studies revealed that VPS13C also promotes ER-SCV contact formation, controls SCV positioning in host cells, and facilitates cell-to-cell spread by the bacteria. Together, our findings highlight the utility of BioID as a tool to study host-pathogen interactions in the context of infection and characterize VPS13C as a novel modulator of the intracellular life cycle of S. Typhimurium. Show less
This study explored latent profiles of Health Information-Seeking Behavior (HISB) among stroke patients and analyzed its influencing factors. In this cross-sectional study, 311 stroke participants fro Show more
This study explored latent profiles of Health Information-Seeking Behavior (HISB) among stroke patients and analyzed its influencing factors. In this cross-sectional study, 311 stroke participants from two tertiary care hospitals in Gansu Province, China, were recruited between January and May 2025 using convenience sampling. Data were collected using a general information questionnaire, the Health Information-Seeking Behavior Scale, and the Health Behavior Decision-Making Assessment Scale for Stroke Patients. Latent profile analysis (LPA) was employed to identify distinct HISB profiles. Three latent profiles were identified: the high-demand low-barrier positive group, the moderate-balanced group, and the low-demand high-barrier negative group. Key predictors of profile membership included age, education level, monthly personal income, and the presence of comorbid chronic diseases. The identification of three distinct HISB trait types provides an evidence-based foundation for developing personalized health education and tailored decision support interventions. Healthcare professionals can leverage this classification system to customize communication strategies for patients with different traits, deliver tiered information support, and ultimately empower patients to achieve better health behaviors and health outcomes. Show less
Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (P Show more
Two-coordinate coinage metal complexes have been exploited for various applications. Herein, a new donor-metal-acceptor (D-M-A) complex PZI-Au-TOT, using bulky pyrazine-fused N-heterocyclic carbene (PZI) and trioxytriphenylamine (TOT) ligands, was synthesized. PZI-Au-TOT displays decent thermally activated delayed fluorescence (TADF) with a quantum yield of 93 % in doped film. The crystals of PZI-Au-TOT show simultaneous TADF, polymorphism, and linearly polarized luminescence (LPL). The polymorph-dependent emission properties with widely varied peaks from 560 to 655 nm are attributed to different packing modes in terms of isolated monomers, discrete π-π stacked dimers or dimer PLUS. Two well-defined microcrystals of PZI-Au-TOT exhibit linearly polarized thermally activated delayed fluorescence with a degree of polarization up to 0.64. This work demonstrates that the molecular rotational flexibility of D-M-A type complexes endows an integration of multiple functions into one complex through manipulation of supramolecular aggregation. This type of complexes is expected to serve as a versatile platform for the fabrication of crystal materials for advanced photonic applications. Show less
To establish an The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model, respectively. Bone marrow transplantation (BMT) mouse model ( Show more
To establish an The 6-8-week-old C57BL/6N female mice and BALB/c female mice were used as the donor and recipient mice of the aGVHD model, respectively. Bone marrow transplantation (BMT) mouse model ( An The adipogenic differentiation capacity of MSCs is inhibited by aGVHD mouse serum. Show less
no PDFDOI: 10.19746/j.cnki.issn.1009-2137.2025.01.038
Limited identification of insulin resistance-associated loci hinders understanding of its role in cardiometabolic health, impeding therapeutic strategies. We apply three multivariate genome-wide assoc Show more
Limited identification of insulin resistance-associated loci hinders understanding of its role in cardiometabolic health, impeding therapeutic strategies. We apply three multivariate genome-wide association study approaches on homeostatic model assessment for insulin resistance, insulin resistance index, fasting insulin, and ratio of triglycerides to high-density lipoprotein cholesterol from MAGIC and UK Biobank to develop a comprehensive phenotype ('mvIR'), and identify 217 independent loci, including 24 novel loci. The mvIR is causally associated with higher risks of 17 cardiometabolic diseases and five aging phenotypes, independent of adiposity and sarcopenia. We outline 21 of 2644 druggable genes for insulin resistance by Mendelian randomization and colocalization, where six genes (AKT1, ERBB3, FCGR1A, FGFR1, LPL, NR1H3) encode targets for approved drugs with consistent directions in alleviating insulin resistance, with no significant side effects revealed by phenome-wide association study. This study uncovers novel loci and therapeutic targets to inform strategies promoting insulin resistance-centered cardiometabolic health and longevity. Show less
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatom Show more
To clarify the anatomical characteristics of the lateral plantar ligament (LPL) of the transverse metatarsal arch (TMA) in the population of southwest Shandong Province, so as to complement the anatomical structures of the midfoot and Lisfranc joint complexes. A total of 100 adult lower limbs were dissected and the types of LPL were divided according to their insertions, among them, 63 were (63%) and 37 were female (37%); 50 were on the left side (50%) and 50 were on the right side (50%). The fiber bundle length, origin width, insertion width, and thickness of the LPL were measured. (1) According to the insertions of the LPL, they were divided into: ① Type I, the LPL was inserted at the base of the second metatarsal (M2) in 47 cases; ② Type II, the LPL was inserted at the base of M2 and fused with tibialis posterior tendon (TPT) in 16 cases; ③ Type III, the LPL was absent in 16 cases; ④ Type IV, the LPL was inserted at TPT in 6 cases; ⑤ Type V, the LPL was inserted at the intermediate cuneiform (IC) in 1 case; ⑥ Type VI, bifid LPL with one bundle inserted at the base of M2, and the other bundle inserted at the medial cuneiform (MC) in 4 cases; ⑦ Type VII, two bundles of LPL inserted at the base of M2 in 8 cases; ⑧ Type VIII, the LPL consisted of 3 bundles; the distal, middle and proximal bundles was inserted at the base of M2, the TPT and the lateral side of navicular bone in 2 cases, respectively. (2) There was a statistical significance in the length of LPL between male (31.62 ± 3.83) mm and female (28.07 ± 3.46) mm (t=-3.050, P = 0.003). There was no statistical significance in the types of LPL between male and female (Z=-1.721, P > 0.05), and no statistical significance in the types between left and right sides (Z=-0.026, P > 0.05). According to our research, LPL originates from M5 and is divided into 8 types according to its insertion location, of which insertion at the base of M2 is the most common. In addition, we found that LPL has fibrous fusion with the long plantar ligament and the TPT, which may be involved in maintaining arch stability. The classification of LPL in this study is a supplement to the anatomical structure of the middle foot and Lisfranc joint complex, providing a new direction for the diagnosis and treatment of middle foot and arch injury in the future. Show less
Jessica Blumenfeld, Yaqiao Li, Min Joo Kim+12 more · 2025 · bioRxiv : the preprint server for biology · Cold Spring Harbor Laboratory · added 2026-04-24
Apolipoprotein E4 (APOE4), the strongest genetic risk factor for late-onset Alzheimer's disease (AD), exacerbates tau tangles, amyloid plaques, neurodegeneration, and neuroinflammation-the pathologica Show more
Apolipoprotein E4 (APOE4), the strongest genetic risk factor for late-onset Alzheimer's disease (AD), exacerbates tau tangles, amyloid plaques, neurodegeneration, and neuroinflammation-the pathological hallmarks of AD. While astrocytes are the primary producers of APOE in the CNS, neurons increase APOE expression under stress and aging. Prior work established that neuronal APOE4 is essential for AD pathogenesis, but whether it is sufficient to drive disease remained unknown. We generated a PS19 tauopathy mouse model selectively expressing APOE4 in neurons. Neuronal APOE4 alone proved sufficient to promote pathological tau accumulation and propagation, neurodegeneration, and neuroinflammation to levels comparable to a tauopathy model with human APOE4 knocked-in globally. Single-nucleus RNA sequencing further revealed similar transcriptomic changes in neurons and glia of both models. Together, these findings demonstrate that neuronal APOE4 alone can initiate and propagate AD pathologies, underscoring its pivotal role in disease pathogenesis and its potential as a therapeutic target. Show less
Qianzhu Jiang, Huiting Li · 2025 · Journal of bioenergetics and biomembranes · Springer · added 2026-04-24
Myocardial fibrosis (MF) is a key pathological process driving heart failure, characterized by excessive extracellular matrix (ECM) deposition and impaired cardiac function. Although myocyte-specific Show more
Myocardial fibrosis (MF) is a key pathological process driving heart failure, characterized by excessive extracellular matrix (ECM) deposition and impaired cardiac function. Although myocyte-specific enhancer factor 2 A (MEF2A) is implicated in cardiac fibroblast activation, its role in MF remains unclear. We manipulated MEF2A expression in cardiac fibroblasts (CFs) through knockdown and overexpression, and assessed fibrosis markers, migration, and RhoA signaling. Binding of MEF2A to the Snail1 promoter was predicted using JASPAR and validated by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. Rescue experiments with Snail1 overexpression and RhoA inhibition were performed. An angiotensin II (Ang II)-induced MF mouse model was used to evaluate cardiac function by echocardiography and to assess collagen deposition through picrosirius red (PSR) staining. MEF2A was significantly upregulated in Ang II-induced fibrotic hearts and CFs. MEF2A knockdown reduced α-SMA and Col1a1 expression, inhibited CF migration, and suppressed activation of the Snail1/RhoA/α-SMA pathway. ChIP and luciferase assays confirmed the direct binding of MEF2A to the Snail1 promoter. Inhibition of RhoA signaling reversed MEF2A-induced myofibroblast activation and migration. Rescue experiments showed that Snail1 overexpression restored the fibrotic phenotype suppressed by MEF2A knockdown. In vivo, MEF2A knockdown improved left ventricular function, reduced collagen deposition (PSR staining), and lowered heart weight/tibia length ratios. MEF2A promotes myocardial fibrosis by directly activating Snail1 and engages the RhoA/α-SMA pathway. Targeting MEF2A offers a promising therapeutic strategy to attenuate MF and improve heart function. Show less
To investigate the influence of MEK5/ERK5 pathway on mitophagy in osteosarcoma (OS), as well as the involved molecular mechanisms. The overlapped genes of mitophagy-related genes from MSigDB database Show more
To investigate the influence of MEK5/ERK5 pathway on mitophagy in osteosarcoma (OS), as well as the involved molecular mechanisms. The overlapped genes of mitophagy-related genes from MSigDB database and DEGs between metastatic and primary OS groups from GSE32981 were identified. GSVA of mitophagy-related pathways between the metastatic and primary groups were analyzed. The relationships between Nur77 and mitophagy-related pathways, prognosis, immune infiltrating cells, immune response gene sets were investigated. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were utilized to assess the expression levels of MEK5, ERK5, Nur77, PINK1, and Parkin. Cellular behaviors and mitochondrial potential were evaluated via CCK-8, Transwell assay and JC-1 staining. Total 4 overlapped genes were obtained as mitophagy-related DEGs, including GABARAPL1, HIF1A, PINK1, and RB1CC1. The activity scores of 3 mitophagy-related pathways exhibited significant differences between metastatic and primary groups. Importantly, Nur77 was significantly negatively correlated with a mitophagy-related pathway (GOBP MITOPHAGY: R = - 0.48, P = 0.02). The Nur77 expression in metastatic group was remarkedly higher than that in the primary group (P < 0.001). Patients with high Nur77 expression had poor prognosis, with AUC values all above 0.615 in predicting 1-, 3-, and 5-year survival. In addition, Nur77 was closely related to numerous immune cells, including activated dendritic cells, activated mast cells and M0 macrophages, and immune response gene sets chemokines and cytokines (all P < 0.05). In addition, MEK5/ERK5 pathway is activated in OS, and Nur77 is overexpressed in OS, and MEK5/ERK pathway promotes Nur77 expression, tumorigenesis and mitochondrial function in U2OS cells. Cytosporone B implement significantly increased the tumorigenesis of U2OS cells in sh-MEK5 group, and inhibited the weaken in mitochondrial membrane potential caused by MEK5 downregulation, and reversed the protein levels of mitophagy markers PINK1 and Parkin in sh-MEK5 group. MEK5-ERK5 pathway mediates mitophagy by regulating Nur77 to promote tumorigenesis of OS cells. These findings offered promising therapeutic targets for OS. Show less
The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive v Show more
The FGFR1 V561M mutation significantly reduces the efficacy of current FGFR1 inhibitors, creating an urgent need for targeted second-generation therapies. In this study, we developed a comprehensive virtual screening protocol that combines energy-based screening and machine learning techniques, leading to the identification of a novel compound, Show less
Colorectal cancer (CRC) is a prevalent digestive system malignancy accompanied by peritoneal metastasis occurring in 7% of cases. Methyltransferase-like 3 (METTL3) promoted the progression of CRC wher Show more
Colorectal cancer (CRC) is a prevalent digestive system malignancy accompanied by peritoneal metastasis occurring in 7% of cases. Methyltransferase-like 3 (METTL3) promoted the progression of CRC whereas its function in peritoneal metastasis was incompletely understood. Here, we found that METTL3 was upregulated in peritoneal metastasis tissues of CRC patients compared with CRC tissues. By sequencing the mRNA of above tissues, we discovered that METTL3-mediated N6-methyladenosine (m6A) modification regulated the downstream target Show less
Melatonin (MLT) can improve mitophagy, thereby ameliorating cognitive deficits in Alzheimer's disease (AD) patients. Hence, our research focused on the potential value of MLT-related genes (MRGs) in A Show more
Melatonin (MLT) can improve mitophagy, thereby ameliorating cognitive deficits in Alzheimer's disease (AD) patients. Hence, our research focused on the potential value of MLT-related genes (MRGs) in AD through bioinformatic analysis. First, the key cells in the single-cell dataset GSE138852 were screened out based on the proportion of annotated cells and Fisher's test between the AD and control groups. The differentially expressed genes (DEGs) in the key cell and GSE5281 datasets were identified, and the MRGs in GSE5281 were selected via weighted gene coexpression network analysis. After intersecting two sets of DEGs and MRGs, we performed Mendelian randomization analysis to identify the MRGs causally related to AD. Biomarkers were further ascertained through receiver operating characteristic curve (ROC) and expression analysis in GSE5281 and GSE48350. Furthermore, gene set enrichment analysis, immune infiltration analysis and correlation analysis with metabolic pathways were conducted, as well as construction of a regulator network and molecular docking. According to the Fisher test, oligodendrocytes were regarded as key cells due to their excellent abundance in the GSE138852 dataset, in which there were 281 DEGs between the AD and control groups. After overlapping with 3,490 DEGs and 550 MRGs in GSE5281, four genes were found to be causally related to AD, namely, G protein-coupled receptor, family C, group 5, member B (GPRC5B), Methyltransferase-like protein 7 A (METTL7A), NF-κB inhibitor alpha (NFKBIA) and RAS association domain family 4(RASSF4). Moreover, GPRC5B, NFKBIA and RASSF4 were deemed biomarkers, except for METTL7A, because of their indistinctive expression between the AD and control groups. Biomarkers might be involved in oxidative phosphorylation, adipogenesis and heme metabolism. Moreover, T helper type 17 cells, natural killer cells and CD56dim natural killer cells were significantly correlated with biomarkers. Transcription factors (GATA2, POU2F2, NFKB1, etc.) can regulate the expression of biomarkers. Finally, we discovered that all biomarkers could bind to MLT with a strong binding energy. Our study identified three novel biomarkers related to MLT for AD, namely, GPRC5B, NFKBIA and RASSF4, providing a novel approach for the investigation and treatment of AD patients. Show less
Long noncoding RNAs (lncRNAs), non-protein-coding transcripts exceeding 200 nucleotides, are critical regulators of gene expression through chromatin remodeling, transcriptional modulation, and post-t Show more
Long noncoding RNAs (lncRNAs), non-protein-coding transcripts exceeding 200 nucleotides, are critical regulators of gene expression through chromatin remodeling, transcriptional modulation, and post-transcriptional modifications. While ionizing radiation (IR) induces cellular damage through direct DNA breaks, reactive oxygen species (ROS)-mediated oxidative stress, and bystander effects, the functional involvement of lncRNAs in the radiation response remains incompletely characterized. Here, through genome-wide CRISPR activation (CRISPRa) screening in non-small cell lung cancer (NSCLC) cells, we identified LOC401312 as a novel radiosensitizing lncRNA, the stable overexpression of which significantly enhanced IR sensitivity. Transcriptomic profiling revealed that LOC401312 transcriptionally upregulates carbamoyl-phosphate synthase 1 (CPS1), a mitochondrial enzyme involved in pyrimidine biosynthesis. Notably, CPS1 overexpression recapitulated the radiosensitization phenotype observed with LOC401312 activation. Mechanistic investigations revealed that CPS1 suppresses the phosphorylation of ATM kinase (Ser1981) protein, which is a key mediator of DNA damage checkpoint activation. This study established the LOC401312-CPS1-ATM axis as a previously unrecognized regulatory network governing radiation sensitivity, highlighting the potential of lncRNA-directed metabolic rewiring to impair DNA repair fidelity. Our findings not only expand the functional landscape of lncRNAs in DNA damage response but also provide a therapeutic rationale for targeting the LOC401312-CPS1 axis to improve radiotherapy efficacy in NSCLC. Show less