👤 Jianping Xiong

Neuropathic pain is a chronic condition initiated by nerve injury and frequently accompanied by affective disturbances, including anxiety and depression. Growing evidence suggests that maladaptive neuroplasticity in the anterior cingulate cortex (ACC) contributes to the persistence and affective dimension of neuropathic pain. To narratively review and critically synthesize current evidence on ACC-related neuroplasticity in neuropathic pain across molecular, circuit, glial, and translational domains. We narratively reviewed experimental and clinical studies addressing ACC-related molecular signaling, synaptic and circuit remodeling, glial and neuroimmune mechanisms, and interventional approaches relevant to neuropathic pain and its affective dimension. At the molecular level, abnormal ACC synaptic plasticity has been associated with long-term potentiation involving N-methyl-D-aspartate (NMDA) receptors-particularly GluN2B-dependent signaling-while the brain-derived neurotrophic factor (BDNF)-TrkB axis may further contribute to dendritic remodeling and maladaptive synaptic strengthening. At the circuit level, the ACC interacts with limbic regions including the insula and amygdala, within distributed networks that appear to contribute to aversive learning and pain-related affect. At the non-neuronal level, alterations in the ACC microenvironment include astrocyte-linked neuroinflammation and microglia-associated synaptic remodeling, which may shift excitation-inhibition balance. Therapeutically, ACC-targeted strategies are evolving from broad pharmacological modulation toward more spatially specific neuromodulation, although major translational challenges remain, including limited target specificity, cross-species differences, and uncertain causal inference in humans. ACC-related neuroplasticity appears to be an important component of neuropathic pain-affect pathophysiology. Future progress will depend on integrating mechanistic insights with network-level interpretation and improving the precision and clinical translatability of ACC-engaging interventions. Show less

Bupivacaine (BUP), a widely used amide-type local anesthetic, exhibits neurotoxic effects. This study aimed to explore the functions of brain-derived neurotrophic factor (BDNF) and methyltransferase Like 3 (METTL3) in BUP-induced hippocampal neuronal damage. HT22 cells and SH-SY5Y cells were treated with various concentrations of BUP. METTL3 and BDNF were manipulated using either overexpression or knockdown approaches to assess their functional roles. Cell viability, apoptosis, mitochondrial membrane potential and oxidative stress markers (Lactate Dehydrogenase (LDH), Reactive Oxygen Species (ROS), Superoxide Dismutase (SOD), Malondialdehyde (MDA)) were evaluated using Cell Counting Kit-8 (CCK-8), flow cytometry, JC-1 staining and commercial kits. The expression of BDNF, METTL3, Caspase-9, Bax and Bcl-2 was analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. The N6-methyladenosine (m6A) modification of BDNF mRNA was assessed using Methylated RNA Immunoprecipitation (Me-RIP) and commercial kits. BUP treatment dose-dependently reduced viability, while increasing oxidative stress and apoptosis in our cellular model. BDNF expression was down-regulated in BUP-induced cells. Additionally, BUP stimulation suppressed both total m6A levels and METTL3 expression in cell models. Overexpression of BDNF ameliorated BUP-induced cell damage. METTL3 stabilized BDNF through m6A modification, and the depletion BDNF reversed the protective effect of overexpressing METTL3 on BUP-induced neurotoxicity. Together, our results indicated that METTL3 attenuated BUP-induced neurotoxicity by enhancing BDNF expression via m6A modification. Show less

Acute hepatitis is a major pathological process underlying acute liver injury (ALI) and acute liver failure (ALF), both of which are associated with high mortality. Yet, no effective treatment is currently available, underscoring the pressing need for novel therapeutic targets. By integrating multiple transcriptomic datasets, this study finds that the expression of brain-derived neurotrophic factor (BDNF) is consistently downregulated in hepatocytes across various ALI/ALF models. Mechanistically, this downregulation is attributed to transcriptional repression of BDNF by RE1-silencing transcription factor. Restoration of endogenous BDNF or exogenous administration of recombinant BDNF significantly alleviates LPS/DGal-induced ALI/ALF. Correlation analysis and proteomic profiling reveal that BDNF exerts potent anti-inflammatory effects by directly binding to and antagonizing Toll-like receptor 4 (TLR4) on macrophages. Structural analysis identifies amino acids 233-244 of BDNF as the key functional domain responsible for this effect. A synthetic 12-mer peptide derived from this region, termed BDP12, retains TLR4-antagonizing ability, demonstrating strong anti-inflammatory efficacy and a favorable safety profile in cultured macrophages and mouse ALI/ALF models. In conclusion, this study identifies hepatocyte-derived BDNF as an endogenous antagonist of TLR4 and a critical immune checkpoint in acute hepatitis. BDNF and its mimetic peptide BDP12 represent promising therapeutic candidates for treating acute hepatitis-mediated ALI/ALF. Show less

Cellular and synaptic plasticity in ventral tegmental area (VTA) play a key role in alcohol use disorder (AUD). Here, we first delineated the in vivo dynamics of dopamine (DA) neuron activity in VTA during chronic intermittent ethanol exposure: initial sensitization was followed by a phase of attenuated and dysregulated response upon the first high-concentration exposure, culminating in stable hyper-responsiveness. Chronic ethanol exposure impaired long-term potentiation of GABAergic synapses (LTP Show less

Peripheral nerve injuries often lead to painful neuroma formation and chronic neuropathic pain, and the optimal surgical strategy for prevention remains debated. Targeted muscle reinnervation (TMR), regenerative peripheral nerve interfaces (RPNI), and nerve-in-muscle implantation (NIM) are surgical techniques developed to mitigate neuroma-related pain, but their relative efficacy has not been compared systematically. This preclinical study compared TMR, NIM, and two RPNI variants in a rat tibial nerve transection model to identify which approach best reduces neuroma formation and pain. Sprague-Dawley rats underwent right tibial nerve transection and were randomized into five groups: control (no repair), NIM, W-RPNI (wrapped RPNI), E-RPNI (embedded RPNI), or TMR. Behavioral outcomes including gait analysis (CatWalk), mechanical hypersensitivity (von Frey test), thermal hyperalgesia (Hargreaves test), and neuroma tenderness were assessed over 12 weeks. At week 12, distal nerve stumps and L4-L5 dorsal root ganglia (DRG) were harvested for histological evaluation, immunohistochemistry/immunofluorescence, and molecular analyses (qRT-PCR and Western blot) targeting pain- and inflammation-related biomarkers. By 12 weeks, TMR-treated rats showed the most robust improvements, including significantly longer stance duration, larger paw contact area, near-baseline withdrawal thresholds, and minimal neuroma tenderness, whereas untreated controls developed gross neuromas and persistent hypersensitivity. TMR also preserved organized nerve architecture with orderly axonal regeneration and minimal collagen I/III fibrosis at the stump. Molecular assays confirmed that TMR markedly attenuated nociceptive and inflammatory signaling, with TMR rats exhibiting the lowest expression of pain-related mediators (c-Fos, TRPA1, TRPV1, CGRP, NPY, BDNF) and pro-inflammatory/fibrotic markers (galectin, α-SMA, IL-1β, TNF-α, TGF-β) in nerve and DRG tissues. Conversely, the anti-inflammatory cytokine IL-10 and axonal ion pump subunits ATP1A2/ATP2B1 were significantly upregulated with TMR. Outcomes for the two RPNI groups were similar to each other and generally intermediate between TMR and control. TMR was superior to RPNI variants and NIM in preventing neuroma formation and alleviating neuropathic pain in this animal model. These findings support TMR as a promising surgical strategy to mitigate post-amputation neuroma pain. Show less

The Angelica sinensis and Ligusticum chuanxiong Herb Pair (DC) serves as a core pairing in Traditional Chinese Medicine for treating blood stasis and blood deficiency syndromes, which are frequently associated with depressive-like symptoms in clinical practice. The antidepressant potential of this combination aligns with its traditional functions of promoting qi circulation, activating blood flow, and alleviating depression. This study aims to investigate the antidepressant effects of DC and its potential mechanisms through a combination of network pharmacology prediction and in vitro and in vivo experimental validation. Network pharmacology screening identified active components and target molecules in DC, constructing a component-target network and validating binding activity through molecular docking. A CUMS-induced rat model of depression was established, with drug efficacy evaluated via behavioral tests (forced swim, sucrose preference, and open field tests) and blood rheology parameters measured. ELISA assay of neurotransmitter and inflammatory factor levels in serum and hippocampal tissue, Observation of histopathological changes in hippocampal tissue using HE and Nissl staining, Western blot and immunofluorescence assays were performed to detect the expression of proteins in the PI3K/AKT pathway. An in vitro inflammatory model was established by inducing BV-2 cells with LPS. The MTT assay was used to screen for the safe concentration of drug-containing serum and observe cell morphology, the Gries method for detecting NO release, ELISA for detecting inflammatory cytokines, Western blot analysis of PI3K/AKT pathway proteins was performed, and pathway inhibition was validated using LY294002. Through network pharmacology analysis, seven major active components of DC and 197 related functional targets for depression treatment were identified, with the majority enriched in the PI3K/AKT signaling pathway. Behavioral studies and in vivo experiments indicate that DC significantly ameliorates depressive-like behaviors in CUMS rats, reduces blood viscosity, increases hippocampal tissue levels of 5-HT, NE, and DA, decreases IL-1β, IL-6, and TNF-α content, and mitigates hippocampal neuronal damage. Western blot and immunofluorescence results indicate that DC can activate the PI3K/AKT pathway, upregulating p-AKT and BDNF expression. In vitro experiments further confirmed that the drug-containing serum could suppress LPS-induced inflammatory responses in BV-2 cells, reducing the release of factors such as NO and IL-1β. This effect was reversible upon treatment with the PI3K inhibitor LY294002. DC exhibits potent antidepressant effects by modulating the PI3K/AKT pathway to enhance neurotransmitter release and reduce inflammatory factor levels. This mechanism protects neurons and alleviates neuroinflammation, thereby exerting antidepressant effects. Show less

The neurotrophic factor (NTF) family has recently expanded its role beyond neurological conditions, but its involvement in acute inflammatory lung diseases remains largely unclear. Using well-established acute lung injury (ALI) and sepsis models, we demonstrate that brain-derived neurotrophic factor (BDNF), a key NTF, is impaired in pulmonary epithelial cells and negatively correlates with the inflammatory response. Raising the BDNF level alleviates inflammatory lung injury, but these effects are absent in macrophage-deleted mice. Both in vivo and in vitro results show BDNF inhibits macrophage inflammation, and further proteomics analysis identifies macrophage TLR4 as a receptor that BDNF antagonizes via direct binding. The BDNF fragment (aa 104-115) is critical for BDNF-TLR4 interaction, and the corresponding synthetic BDNF-derived dodecapeptide (BDP-12) retains TLR4-antagonistic and anti-inflammatory effects both in vitro and in vivo, without pro-proliferative side effects. In conclusion, our findings reveal that epithelial-derived BDNF prevents macrophage inflammation by directly targeting TLR4 and highlights BDP-12 as a potential therapeutic agent for acute inflammatory diseases. Show less

The pathological mechanism of Alzheimer's disease (AD) is complex. The binding of Aβ to α7 nicotinic acetylcholine receptor (α7nAChR) contributes to neuronal damage. Sinomenine (SIN) is an alkaloid extracted from the traditional Chinese medicine Qingfengteng (Sinomenium acutum). The anti-inflammatory, antioxidant, and immunomodulatory effects of SIN were confirmed to be closely associated with the α7nAChR. This study aimed to investigate whether α7nAChR serves as a pharmacological target of SIN against AD, and to evaluate the neuroprotective effects of SIN both in vivo and in vitro, focusing on the α7nAChR/Nrf2/Keap1 signaling pathway. In this study, the effects of SIN in both APP/PS1 transgenic mice and SH-SY5Y cells subjected to Aβ1-42-induced injury were assessed. The selective antagonist α-bungarotoxin ‌(α-BTX), the agonist nicotine (Nic) of α7nAChR, and α7nAChR siRNA were employed. The cognitive function, Aβ deposition, synaptic plasticity markers, the tau protein phosphorylation, mitochondrial membrane potential, oxidative stress and the α7nAChR/Nrf2/Keap1 signaling pathway were analyzed in vivo and/or in vitro. SIN significantly enhanced learning and memory abilities in APP/PS1 mice, reduced Aβ plaque deposition and synaptic dysfunction, and inhibited hyperphosphorylation of tau protein and oxidative stress in the brain. In Aβ1-42-induced neuronal injury model, SIN alleviated apoptosis, increased BDNF and ACh levels, inhibited mitochondrial damage, stabilized calcium homeostasis, and suppressed oxidative stress. Meanwhile, SIN disrupted Nrf2-Keap1 binding to promote the Nrf2/HO-1 signaling pathway. Nevertheless, SIN effects above were inhibited by α-BTX. The knockdown of α7nAChR in vitro significantly promoted Nrf2/HO-1 pathway and BDNF expression. SIN exerts neuroprotective effect in APP/PS1 transgenic mice and Aβ1-42-induced neuronal injury by inhibiting oxidative stress via α7nAChR/Nrf2/Keap1 pathway. This study provides evidence for α7nAChR as a new target and the clinical application potential of SIN in AD treatment. Show less

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are debilitating disorders with overlapping symptoms such as chronic pain and fatigue. Dysregulation of the endogenous opioid system, particularly µ-opioid receptor function, may contribute to their pathophysiology. This study examined whether epigenetic modifications, specifically µ-opioid receptor 1 gene ( Show less

Visceral pain is frequently accompanied by depression, a comorbidity involving central neuroinflammation and abnormal neuronal plasticity. The P2X7 receptor (P2X7R) plays a crucial role in neuroinflammation and pyroptosis, while Jujuboside A (JuA), a major saponin extracted from Ziziphus jujuba seeds, has been reported to exert significant antidepressant and analgesic effects. In this study, we systematically evaluated the regulatory effects of JuA on the P2X7R-brain-derived neurotrophic factor (BDNF) pathway and on pyroptosis and apoptosis using a rat model of colorectal distension (CRD) and primary neuron/astrocyte cultures. JuA markedly alleviated visceral hypersensitivity and depressive-like behaviors in CRD rats and reduced P2X7R expression in both the spinal cord (SC) and hippocampus (HPC). Further investigations in vitro revealed that JuA inhibited excessive P2X7R activation in SC astrocytes, thereby decreasing the expression of NLRP3, Caspase-1, GSDMD, IL-1β and TNF-α, indicating suppression of pyroptosis. Similarly, JuA exerted an anti-pyroptotic effect in HPC astrocytes and inhibited neuronal apoptosis by reducing Caspase-3 and Bax levels while increasing Bcl2 expression, leading to upregulation of HPC BDNF. Collectively, JuA targets P2X7R and suppresses downstream pyroptotic and apoptotic signaling in vitro, which may contribute to its neuroprotective effects. These findings provide experimental evidence supporting the potential of JuA as a therapeutic agent for comorbid visceral pain and depression. Show less

Electroconvulsive therapy (ECT) stands as the most effective intervention for treatment-resistant depression; however, its interaction with dietary regulation of the gut-brain axis has not been thoroughly explored. This study aimed to elucidate the mechanistic link between ECT, gut microbiota remodeling, short-chain fatty acid (SCFA) production, and neural plasticity. In this study, mice were subjected to chronic restraint stress (6 h/d for 28 consecutive days) to establish a depression-like model. Utilizing a translational approach that incorporated behavioral assessments, multimodal neuroimaging techniques such as PET-CT and laser speckle contrast imaging, along with multiomics analyses including metagenomics, metabolomics, and transcriptomics in rodent models, we demonstrated that ECT induced significant gut microbiota remodeling, characterized by an enrichment of SCFA-producing genera like Lactobacillus and Bifidobacterium. This remodeling was associated with restored intestinal barrier integrity and elevated plasma SCFA levels. Mechanistically, these microbial metabolites activated hippocampal Wnt/β-catenin signaling pathways, enhancing synaptic plasticity restoration, while concurrent probiotic supplementation further amplified brain-derived neurotrophic factor (BDNF) expression via SCFA-dependent epigenetic mechanisms. Neuroimaging corroborated the normalization of cerebral glucose metabolism and hemodynamic function post-ECT. In conclusion, our findings unveil a novel gut-brain communication pathway by which ECT exerts its antidepressant effects, positioning SCFAs as vital mediators connecting microbial metabolic alterations to neural plasticity. This research not only redefines the role of nutritional biochemistry in neuromodulation but also suggests the potential of microbial metabolite monitoring to tailor antidepressant therapies for enhanced efficacy. Show less

This pilot study investigated the protective effect of transfecting brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (bcl-2) genes in retinal ganglion cells (RGCs) using in vivo electroporation in an adult rat optic nerve transection model. Sprague-Dawley rats were randomly divided into five groups: BDNF(+)/bcl-2(+), BDNF(+), bcl-2(+), empty plasmid (EP), and no surgery (NS). The plasmids were intravitreally injected and electroporated into the left eye. Seven days later, optic nerve transection was performed in all groups except the NS group. Protein expression was examined using Western blotting, RGC survival was quantified using 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI) retrograde labeling, and apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) at multiple time points (7, 14, and 28 d after transfection). A significantly higher number of DiI (+) RGCs and lower number of apoptotic cells were observed in the BDNF(+)/bcl-2(+), BDNF(+), and bcl-2(+) groups compared to those in the EP group at all time points. The number of DiI (+) RGCs in the three treatment groups was significantly lower than that in the NS group. However, there were no significant differences among the three treatment groups. The protective effects of gene transfection tended to be strongest in the BDNF(+)/bcl-2(+) group, followed by the BDNF(+) group and then the bcl-2(+) group. Thus, all gene transfection treatments had a protective effect against the loss of DiI(+) RGCs induced by optic nerve transection but did not result in full recovery. This study also confirmed the value of in vivo electroporation. The findings of this pilot study provide a working base for the development of gene therapy for blinding optic nerve disorders. Show less

Anoikis resistance and epithelial-mesenchymal transition (EMT) are crucial factors in tumor invasiveness and metastasis in lung adenocarcinoma (LUAD). Identifying anoikis-EMT-related genes could be beneficial for predicting prognosis and immunotherapeutic efficacy in patients with LUAD. This study aims to establish and validate a novel prognostic signature based on anoikis-EMT-related genes for LUAD and to identify the potential biomarkers encapsulated within it. Anoikis-related genes and EMT-related genes were retrieved from the GeneCards and dbEMT 2.0 databases. Univariate Cox regression analysis and principal component analysis (PCA) were conducted to define anoikis and EMT levels. Gene expression and clinical information of patients with LUAD were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Univariate Cox regression and multivariate Cox regression analyses were conducted to construct a risk score model. Immune correlation and drug sensitivity analyses were performed to investigate the association of the risk score with the immune profile and antitumor treatment. Three essential genes in the model were examined for messenger RNA (mRNA) expression by reverse transcription-polymerase chain reaction (RT-PCR) and for protein levels via the Human Protein Atlas (HPA) database. LUAD patients demonstrating low Anoikis Potential Index (API) combined with high EMT Potential Index (EPI) exhibited the poorest overall survival (OS). We further constructed a nine-gene prognostic risk model that combines anoikis and EMT. High-risk patients demonstrated significantly shorter survival duration. The clinical-prognostic nomogram accurately predicted outcomes at 1, 3, and 5 years. In addition, patients in low-risk group demonstrated superior immune responses to treatment and were more sensitive to commonly used chemotherapy drugs. Our validation studies confirmed upregulated expression of ANGPTL4, SLC2A1, and BIRC5 in LUAD, observed at both transcriptional and translational levels. The anoikis-EMT-based risk model effectively forecasts both OS and immunotherapy response in LUAD patients, accelerating the identification of groundbreaking molecular biomarkers and prospective molecular targets. Show less

Rapid platelet inhibition is essential for effective management during emergency percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). However, the oral dosage form of clopidogrel (CLP) commonly used in clinical practice shows a delayed onset due to gastrointestinal absorption, first-pass metabolism, and the requirement for hepatic cytochrome P450 (CYP450)-mediated bioactivation, which limits its applications in urgent scenarios and complicating post-PCI bleeding management. To address these challenges, we developed an intravenous micellar formulation (CLP/PM) using FDA-approved mPEG-PLA copolymers to promote rapid hepatic exposure and metabolic activation. By tuning the PLA chain length, micellar core density and PEG conformation were modulated, thereby influencing protein corona (PC) formation and liver-affinity interactions. Proteomic profiling revealed that micelles with intermediate PLA length selectively recruited liver-affinity apolipoproteins (ApoM, ApoH, ApoA1, and ApoB), which are known ligands of LDLR and SR-BI, while minimizing adsorption of inflammatory and opsonization proteins. The optimized CLP/PM (3.9 k) exhibited a hepatotropic-like PC that was associated with hepatocyte-enriched uptake in primary liver cell analyses. In vivo biodistribution showed rapid liver-level signal, and pharmacokinetic studies supported enhanced CYP450-mediated activation, achieving a higher C Show less

The gut microbiota is a diverse and abundant microbial community in animals; it plays a key role in nutrient absorption and immune defense and is an important factor affecting chicken health and growth performance. Understanding the composition of chicken gut microbiota and its influencing factors can provide a theoretical foundation for maintaining the diversity and microecological balance of beneficial microbial communities in the chicken intestinal tract. This review aimed to explore the recent advancements in understanding the non-genetic e.g. environmental and host genetic factors that influence the chicken gut microbiome, focusing on the gut microbial composition including host genetic kinship, heritability, microbial quantitative loci, and candidate genes. Studies on host genetic factors have identified several genes associated with gut microbial composition including lipid droplet associated hydrolase (LDAH) and apolipoprotein B (APOB) associated with Staphylococcus; TOX high mobility group box family member 2 (TOX2) significant locus linked to Veillonella, and reelin (RELN), lumican (LUM), and S-phase cyclin A associated protein in the ER (SCAPER) associated with intestinal microbial abundance. These factors are involved in host growth, development, and immune system regulation, collectively indicating that host genes play a significant role in regulating chicken gut microbiota. Furthermore, a comprehensive exploration of both non-genetic and host genetic factors could provide a solid foundation and practical strategies for improving chicken health and production performance by regulating the gut microbiota. Show less

The therapeutic effects of different combination therapies containing cholesteryl ester transfer protein (CETP) inhibitors vary. Evidence from head-to-head comparisons is scarce and inconsistent. This study aimed to evaluate the impact of CETP inhibitor-based combination therapy on lipid levels and explore its adverse events (AEs). Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, Cochrane Library, and Web of Science up to August 30, 2025. Thirteen RCTs were analyzed through STATA 14.0. This systematic review and network meta-analysis of 13 studies (9248 participants) evaluated CETP inhibitor-based combination therapies. For HDL-C elevation, obicetrapib + ezetimibe + statin ranked highest (SUCRA = 95.1%). Evacetrapib + statin achieved reduction in LDL-C (SUCRA = 94.3%). Obicetrapib + ezetimibe + statin excelled in reducing TC (SUCRA = 100.0%) and TG (SUCRA = 99.9%). Obicetrapib + statin was most effective for ApoAI increase (SUCRA = 100.0%), while obicetrapib + ezetimibe + statin best reduced ApoB (SUCRA = 100.0%). Regarding safety, obicetrapib + statin had the optimal profile for all grade AEs (SUCRA = 19.2%) and severe AEs (SUCRA = 22.5%), conversely, evacetrapib + statin had the worst profile (SUCRA = 83.1% and 66.3%, respectively). Our meta-analysis demonstrated that CETP inhibitor combination therapies offer distinct lipid-modulating benefits and safety profiles. The obicetrapib + ezetimibe + statin triple therapy showed superior comprehensive efficacy, while obicetrapib + statin exhibited the optimal safety. Evacetrapib + statin provided potent LDL-C reduction but had the poorest safety. These findings facilitate personalized treatment selection for dyslipidemia management. PROSPERO CRD420251145396 ( https://www.crd.york.ac.uk/prospero/ ). Show less

To observe the effect of moxibustion on the lipid metabolism, aortic arch and mitochondrial structure, PTEN-induced kinase 1 (PINK1)/Parkin signaling pathway, and the expressions of apoptosis-related proteins in atherosclerotic (AS) mice, so as to explore its potential mechanisms underlying prevention and treatment of AS. Ten C57BL/6J mice were fed with normal chow and used as the control group. Thirty ApoE Compared with the control group, the contents of serum TC, TG and LDL-C, expression levels of PINK1, Parkin, Bax and Caspase3 protein, and the immunoactivity of Parkin and Cyt C were significantly increased ( Moxibustion can improve the lipid metabolism level, relieve pathological injury of the thoracic aorta, restore mitochondrial structure and function in ApoE Show less

Structural MRI analysis for Alzheimer's disease (AD) is limited by balancing group-level comparability in standard space with anatomical fidelity in native space. We therefore propose a multi-space, hybrid-feature framework, integrating radiomics and network metrics from both spaces to classify AD and predict mild cognitive impairment (MCI) progression. An integrated dual-space analytical framework was applied to T1-weighted MRI data. Models were developed on 1,477 participants from Alzheimer's Disease Neuroimaging Initiative (ADNI) and externally tested on an independent cohort of 1,349 participants from National Alzheimer's Coordinating Center (NACC). The framework extracts parallel radiomic and graph-based network features from both Montreal Neurological Institute (MNI) standard space and native space. These features were used to build machine learning models for three-class diagnosis (NC vs. MCI vs. AD) and 6-year prognostic prediction of MCI-to-AD conversion. For each task, the models using standard-space, native-space, and combined-space features were systematically compared. Model interpretation was performed using Shapley Additive Explanations (SHAP), and the features were validated against established AD biomarkers. The combined-space model demonstrated superior performance in both diagnostic classification (Macro-Averaged AUC: 0.96 in ADNI cohort, 0.94 in NACC cohort) and prognostic prediction of MCI-to-AD conversion (C-index: 0.83; HRs: 7.60, 95%CIs: 4.57-12.64). The extracted features in the ADNI cohort demonstrated significant correlations with APOE ε4 genotype, cognitive scores, and CSF biomarkers. Integrating multi-scale features from both standard and native spaces enhances AD diagnosis and prognosis accuracy more effectively than conventional single-space analysis. Show less

Atherosclerosis (AS) is linked to many cardiovascular disorders. We investigated the potential roles and mechanisms of microRNA (miR)-218-5p in AS. Primary mouse aortic endothelial cells (MAECs) were induced with ox-LDL, followed by various interventions including miR/gene overexpression and knockdown. An AS mouse model was established in ApoE Show less

Thin endometrium (TE), affecting 1.5 %-9.1 % of reproductive-aged women, emerges as a disturbed decidua microenvironment underpinning implantation failure and recurrent pregnancy loss. Through integrated single-cell transcriptomics with histopathology and multiplex immunofluorescence (TSA) validation, we delineated TE as a disease of coordinated repairment impairment and pro-fibrotic remodeling across stromal and immune compartments. Key findings revealed a pathological imbalance in stromal subsets, including the decrease of regenerative IGFBP3 + Stromal₁ cells and expansion of fibrogenic Stromal₂ populations, driving collagen-dominant extracellular matrix remodeling. Concurrently, immune dysfunction was unmasked. NK cells decreased and shifted from immune surveillance to a pro-inflammatory phenotype, T cells transitioned from immune regulation to extracellular matrix remodeling effectors and macrophages adopted a pro-fibrotic phenotype with lipid metabolic collapse. CellChat analysis pinpointed suppression of GZMA-PARD3 and APOE-TREM2 axes as drivers of stromal dysfunction, while the hyperactivated adhesion (LAMA3) and collagen pathways served as central mediators of the fibro-inflammatory cascade. These findings, based on single-cell RNA-seq and spatial verification, suggest therapeutic targets for restoring endometrial homeostasis in TE. These findings suggested that TE as a disease of progressive stromal-immune fibrosis dysregulation, offering novel therapeutic targets to restore endometrial repairment and microenvironmental homeostasis. Show less

Vascular senescence is a fundamental driver of age-related cardiovascular diseases, yet the epigenetic mechanisms controlling this process remain poorly understood. This study investigated the role and underlying mechanisms of lysine acetyltransferase 8 (KAT8), a key histone acetyltransferase, in maintaining endothelial cell homeostasis and preventing vascular senescence. We found that KAT8 expression is consistently downregulated in human aged vessels, senescent rats and mice, and cellular models of aging. Using CRISPR-Cas9-based loss-of-function and gain-of-function approaches in endothelial cells, C57BL/6J mice, and ApoE Show less

Precise toxicological mechanism of atherosclerosis (AS) induced by environmental hazardous substance nicotine exposure remains unclear, impeding its prevention strategies and antagonist development. Additionally, it is yet unknown whether Dendrobium officinale's active components can antagonize nicotine-induced AS. This study aimed to elucidate nicotine exposure-induced AS toxicological mechanisms and identify Dendrobium officinale's active components-derived antagonists. Firstly, using ApoE Show less

Atherosclerosis is a chronic inflammatory disease marked by lipid accumulation and immune cell infiltration in arterial walls. Macrophages contribute by internalizing oxidized low-density lipoprotein, forming foam cells, and driving inflammation. The ubiquitin-proteasome system regulates immune and inflammatory responses in atherosclerosis. This study investigated the protective role of TRIM31 (tripartite motif-containing 31), an E3 ubiquitin ligase, in macrophage lipid metabolism and inflammation through selective regulation of LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1). Transcriptomic profiling, macrophage-specific TRIM31 was selectively upregulated in macrophages under oxidized low-density lipoprotein stimulation and in atherosclerosis plaques. Trim31 deficiency exacerbated plaque burden, foam cell formation, and inflammatory signaling (n=8 per group). Single-cell analysis revealed enrichment of lipid transport and inflammatory pathways in Trim31-deficient plaques. LOX-1 was identified as a key TRIM31 substrate. TRIM31 promoted K48-linked ubiquitination of LOX-1 at lysine 12, facilitating its degradation. The atheroprotective effects of Trim31 were abolished in TRIM31, an inducible, macrophage-enriched protective factor in atherosclerosis, restricts foam cell formation and inflammation by targeting LOX-1 for proteasomal degradation. These findings position TRIM31 as a promising therapeutic target for macrophage-driven atherogenesis. Show less

Vascular smooth muscle cells (VSMCs) contribute to atherosclerotic foam cell formation, but mechanisms regulating their phenotypic switching and programmed cell death remain unclear. O-GlcNAcylation, a nutrient-sensitive post-translational modification implicated in vascular calcification, lacks defined roles in VSMC foam cell biology. Inducible smooth muscle-specific Ogt knockout mice on an Apoe OGT expression and global O-GlcNAcylation were reduced in VSMCs during atherogenic progression. Ogt deletion in VSMCs promoted foam cell formation with enhanced lipid accumulation but paradoxically reduced atherosclerotic lesion area concurrent with increased intraplaque cell death. Both genetic and pharmacological OGT inhibition recapitulated this duality in vitro, simultaneously accelerating lipid accumulation while triggering PANoptosis, as evidenced by concurrent activation of cleaved caspase-3, phosphorylated MLKL, and cleaved GSDMD. Individual inhibition of apoptosis, necroptosis, or pyroptosis provided only partial rescue. OGT acts as a dual regulator of VSMC fate, attenuating plaque burden through PANoptosis induction while promoting foam cell formation, revealing its complex role in atherosclerosis pathogenesis and suggesting context-dependent therapeutic implications. Show less

To investigate cognitive status in patients with interstitial lung disease (ILD) and its association with lung tissue transcriptomic alterations, and to propose potential lung-brain interaction mechanisms and clinical implications. We enrolled 45 ILD patients and 45 age-matched controls and compared Mini-Mental State Examination (MMSE) total and subscale scores. Baseline laboratory and pulmonary function characteristics of ILD were summarized. Using lung tissue RNA-seq data from GSE213001 {29 ILD cases [20 idiopathic pulmonary fibrosis (IPF), 9 non-IPF], 14 non-diseased controls [NDC], totaling 139 samples}, we performed PCA, differential expression analysis using the limma-voom framework with the duplicate Correlation function to account for within-donor correlations (threshold |log ILD patients showed significantly lower MMSE total scores than healthy controls, with notable declines in attention/calculation and orientation. At the transcriptomic level, PCA clearly separated ILD from NDC, whereas IPF and non-IPF did not form distinct subgroups. Differential analysis identified 1,544 DEGs (1,142 upregulated; 402 downregulated). Enrichment analysis confirmed strong signals for inflammatory and fibrotic pathways. In an exploratory analysis, we also observed enrichment for terms related to nervous system function. The expression trends of several genes previously implicated in neurocognitive contexts, including PSEN1, PSEN2, BACE1, showed a directional concordance with patterns described in neurodegenerative contexts. This study provides preliminary evidence linking ILD to cognitive impairment on screening and identifies intriguing overlaps between lung tissue transcriptomic alterations and pathways relevant to brain function. These convergent observations lend biological plausibility to, and motivate further investigation of, a lung-brain axis hypothesis in ILD. The findings highlight the need to consider cognitive health in ILD management and warrant validation in longitudinal cohorts with detailed neuropsychological phenotyping. Show less

Alzheimer's disease (AD), the most prevalent form of dementia, is characterized as a slowly progressing neurodegenerative disease marked by senile plaques and neurofibrillary tangles due to the buildup of amyloid-beta peptide (Aβ) and phosphorylated tau in the brain. It is reported that arctigenin (ATG) reduces the level of the enzyme 1 that cleaves β-site amyloid precursor protein and increases Aβ clearance by enhancing autophagy. Compound ARC-18 is a derivative of ATG. The main objective of this study is to investigate whether ARC-18 could improve cognitive function and disease progression by promoting autophagy in Alzheimer-like animal models. Three-month-old 5 × FAD mice were orally treated with the drug for three consecutive months. Water maze and novel object recognition were used to assess cognitive abilities of 5 × FAD mice. In the hippocampus of the mice' brain, APP processing-related proteins (sAPP Show less

Nitrogen metabolism plays a key role in maintaining normal physiological functions of the organism and cell proliferation and differentiation. Nitrogen metabolism in normal human body maintains a dynamic balance to meet the body's demand for synthesis of biological macromolecules such as proteins and nucleic acids. However, in the process of tumor development, the nitrogen metabolism of tumor cells is reprogrammed to meet the demand of rapid proliferation, showing significantly different metabolic characteristics from normal cells. Key enzymes in the tumor microenvironment affect nitrogen metabolism through multiple mechanisms, providing essential nitrogen sources and energy for tumor cells. In-depth exploration of the regulatory mechanisms of tumor nitrogen metabolism not only helps to reveal the molecular basis of tumor development, but also provides a theoretical basis for the development of new tumor therapeutic strategies. In this paper, the relationship between nitrogen metabolism and tumors is systematically elaborated from the characteristics of nitrogen metabolism in normal people, the reprogramming of nitrogen metabolism in tumor patients, the influence of key enzymes on nitrogen metabolism in the tumor microenvironment, as well as the mechanism of tumor nitrogen metabolism regulation, etc., so as to provide references for the related research. Show less

This study aims to construct a prognostic model for hepatocellular carcinoma (HCC) based on palmitoylation-related genes and explore its molecular mechanisms through multi-dimensional analyses. The research integrated single-cell transcriptome data (GSE189903) with bulk transcriptome data (TCGA-LIHC, GEO datasets), focusing on palmitoylation-related genes in HCC epithelial cells. The scAB deconvolution algorithm was used to analyze the association between epithelial cell subsets and patient survival, and hdWGCNA was combined to construct a gene co-expression network. Through differential expression analysis, univariate Cox regression, and LASSO penalized regression, 7 key genes (SERPINE1, FMO3, ALDH2, CPS1, SLCO1B1, ACAT1, ACADS) were identified to build a prognostic risk model. Validation results showed that the model could effectively distinguish the survival prognosis of high-risk and low-risk patients (AUC values for 1/3/5 years in the TCGA cohort were 0.676, 0.656, and 0.642, respectively; those in the GSE14520 validation set were 0.702, 0.658, and 0.654, respectively), and the risk score was an independent prognostic factor. Further analyses revealed that the risk score was associated with tumor staging, immune cell infiltration (e.g., T cells, monocytes), response to immunotherapy, and drug sensitivity. Functional enrichment analysis indicated that the high-risk group was enriched in cell cycle regulation and oncogenic signaling pathways, while the low-risk group was related to metabolic pathways. This study is the first to analyze the regulatory network of palmitoylation in HCC epithelial cells by combining single-cell and bulk transcriptomes, providing new molecular targets and methodological references for HCC prognosis evaluation and precision therapy. Show less