The pathological environment of atherosclerosis (AS) is characterized by hyperlipidemia and chronic inflammation, which cause increased heterogeneity among vascular smooth muscle cells (VSMCs). Owing Show more
The pathological environment of atherosclerosis (AS) is characterized by hyperlipidemia and chronic inflammation, which cause increased heterogeneity among vascular smooth muscle cells (VSMCs). Owing to its lipid-regulating and anti-inflammatory effects, paeoniflorin (Pae) inhibits VSMC phenotypic transformation, making it a promising candidate for AS treatment. Mouse aortic VSMCs were treated with oxidized low-density lipoprotein (ox-LDL) and Pae, and the effects on cell phenotype were examined. An AS model was established by feeding ApoE Pae reversed weight gain and elevated TG levels in the AS model. Oil Red O staining showed that Pae inhibited VSMC-derived foam cell formation in vitro and reduced aortic sinus plaque area, aortic wall lipid deposition, and hepatic steatosis in the AS model. Immunofluorescence staining of the aortic sinus revealed that Pae mitigated α-SMA overexpression and reversed ATP-binding cassette transporter A1 (ABCA1) downregulation. Western blotting analysis revealed that Pae inhibited ERK1/2 and p65 phosphorylation, curbed MMP2 overexpression, and restored downregulated ABCA1 expression. Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine staining, and wound healing assays demonstrated that Pae inhibited ox-LDL-induced VSMC proliferation and migration. Additionally, Pae significantly inhibited the expression of the inflammatory factors IL-6 and MCP-1 both in vivo and in vitro. Pae may treat AS by inhibiting VSMC phenotypic transformation. Show less
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have revolutionized cancer therapy, yet primary and acquired resistance remain major clinical obstacles. Dysregulated angiogenesis fue Show more
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have revolutionized cancer therapy, yet primary and acquired resistance remain major clinical obstacles. Dysregulated angiogenesis fuels the development of an immunosuppressive tumor microenvironment, while crosstalk between immunity and angiogenesis further propels tumor immune evasion and treatment resistance. The present study aimed to establish a penpulimab-resistant model, delineate anti-PD-1 resistance traits via single-cell RNA sequencing, and unravel the precise mechanisms through which anlotinib-an anti-angiogenic agent-mitigates penpulimab resistance. These findings offer insights to guide clinical management of immune-pretreated patients. Single-cell sequencing analyses demonstrated that anlotinib reverses penpulimab resistance by reprogramming the tumor immune microenvironment, thereby boosting PD-1 blockade efficacy via modulation of immune infiltration and tumor signaling pathways. Identifying Apoe⁺ M2 macrophages, Srgn⁺ M1 macrophages, and Cxcl2⁺ T cells provides key cellular and molecular targets for developing clinically actionable immunotherapies. Taken together, this work validates the preclinical potential of anlotinib combined with immunotherapy for immunotherapy-resistant tumors. Show less
Haojie Ni, Yiyi Xiong, Min Liu+14 more · 2026 · Phytomedicine : international journal of phytotherapy and phytopharmacology · Elsevier · added 2026-04-24
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 ex Show more
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
Hepatitis B virus (HBV) infection can cause liver damage through oxidative stress (OS) and immune-inflammatory responses. This study aims to explore the clinical significance of fibroblast growth fact Show more
Hepatitis B virus (HBV) infection can cause liver damage through oxidative stress (OS) and immune-inflammatory responses. This study aims to explore the clinical significance of fibroblast growth factor 21 (FGF21) in the development and progression of chronic hepatitis B (CHB). A total of 336 participants were recruited, including 320 CHB patients and 16 healthy controls. The expression of FGF21, immune cytokines, and OS-related molecules in peripheral blood mononuclear cells (PBMCs) was detected using real-time quantitative polymerase chain reaction. The methylation level of the FGF21 gene promoter in PBMCs was detected using TaqMan probe-based quantitative methylation-specific PCR. The expression level of FGF21 in the peripheral blood of CHB patients was higher than that of HC, but the methylation level of the FGF21 promoter was lower than that of HC, especially in patients during the immune activation phase. The mRNA expression levels of CXCR3 and CCL5 in PBMCs of CHB patients during the immune activation and reactivation phases were higher than those in other clinical stages. Single-cell analysis revealed that CXCR3 and CCL5 expression in the immune tolerance and immune activation phases with high HBsAg expression was closely related to T lymphocytes (T cells) and natural killer cells (NK cells) and was highly expressed in CD4 and CD8 T cells and NK cells. In addition, the mRNA expression levels of Nrf2 and GPX4 in the reactivation phase were higher than those in other clinical stages. The mRNA expression level and methylation level of FGF21 in PBMCs of CHB patients were correlated with the viral load, immune inflammation, and OS levels during the antiviral treatment course of CHB. The methylation level of the FGF21 promoter has the potential to become a non-invasive biomarker for monitoring the progress of antiviral treatment in CHB.IMPORTANCEThis study conducted an in-depth exploration of the application of methylation detection technology, analyzing its value and driving mechanism in the oxidative stress and immune-inflammatory balance during the course of chronic hepatitis B. The study analyzed the methylation patterns of the FGF21 promoter and the expression levels of its receptor FGFR1, as well as the expression levels of chemokines CXCR3, CCL5, and oxidative stress factors GPX4 and Nrf2 in the immune tolerance period, immune clearance period, immune control period, and reactivation period of chronic hepatitis B. It clarified the association between these molecules and the FGF21/FGFR1 axis and revealed the synergistic or antagonistic mechanisms of these molecules in the oxidative stress and inflammatory vicious cycle. At the same time, this study also explored the value of FGF21 promoter methylation in disease diagnosis and prognosis, providing a theoretical basis for evaluating the antiviral treatment effect and disease progression of chronic hepatitis B. Show less
Cerebrospinal fluid (CSF) proteomics offers insights into molecular changes in aging and Alzheimer's disease (AD). Key AD biomarkers, in particular amyloid-β (Aβ) and tau, in CSF are strongly associat Show more
Cerebrospinal fluid (CSF) proteomics offers insights into molecular changes in aging and Alzheimer's disease (AD). Key AD biomarkers, in particular amyloid-β (Aβ) and tau, in CSF are strongly associated with Show less
Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. Howev Show more
Rising global temperatures lead to a continuous increase in the frequency and intensity of extreme weather events, such as droughts and floods, posing serious threats to terrestrial homeotherms. However, adaptive changes in respiratory metabolism and molecular mechanisms in lung tissues of small mammals under extreme water shortage conditions remain unclear. This study hypothesized that small desert mammals can adapt to extreme water shortage environments by regulating the plasticity of lung tissue gene expression and respiratory metabolism. Using 29 wild-caught Siberian jerboas ( Show less
Malachy Bishop, Jian Li · 2026 · Work (Reading, Mass.) · SAGE Publications · added 2026-04-24
BackgroundMultiple sclerosis (MS) is a prevalent, frequently progressive condition of the central nervous system that can significantly affect employment and career participation. Although researchers Show more
BackgroundMultiple sclerosis (MS) is a prevalent, frequently progressive condition of the central nervous system that can significantly affect employment and career participation. Although researchers have extensively catalogued the factors that people with MS face in maintaining employment, the priorities of people working with MS in terms of career resources and information needs have not been extensively evaluated.ObjectiveWe sought (a) to identify the types of career information and resources that employed or recently-employed people with MS prioritize, and (b) to assess the extent to which the need for these career resources may vary among identifiable subgroups.MethodDescriptive statistics and latent profile analysis (LPA) were applied to the responses of 376 iConquerMS members who were either employed ( Show less
Schizophrenia (SCZ) is a complex psychiatric disorder, and its pathogenic mechanisms are not yet fully understood. The identification of reliable blood biomarkers and molecular subtypes for early diag Show more
Schizophrenia (SCZ) is a complex psychiatric disorder, and its pathogenic mechanisms are not yet fully understood. The identification of reliable blood biomarkers and molecular subtypes for early diagnosis and effective therapy remains a significant challenge. To address this issue, we utilized a combination of bioinformatics and machine learning (ML) to identify potential biomarkers for SCZ. Our approach involved the integration of 12 different ML algorithms to develop a diagnostic signature based on data from several datasets, including GSE18312, GSE27383, GSE38485, GSE54913, and GSE165604. A nomogram was constructed using these datasets for potential clinical applications. In addition, clustering analysis was performed on SCZ patients using consensus clustering and non-negative matrix factorization (NMF) algorithms. We further evaluated subtype differences in biological functions and immune cells through various methods, such as gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), Proteomaps, and IOBR analyses. Our results identified a diagnostic signature composed of 16 genes (APBB2, CLCN1, SYDE1, PAX5, SNAI1, DAZL, UNC93B1, PLAGL2, HS3ST1, ITPKB, PILRA, BTLA, SWAP70, AZI2, ADM, and AVPR2), which demonstrated robust performance in diagnosing SCZ across eight different datasets. A nomogram based on these genes was created, providing clinical benefits for SCZ patients. Among the identified genes, AZI2 was found to be the most critical, influencing inflammation and immunity. We also identified potential chemical compounds that could target these 16 genes. Unsupervised clustering and NMF algorithms revealed two distinct subtypes of SCZ, each associated with unique immune cell profiles, biological functions, and protein expression levels. In conclusion, this study not only developed a diagnostic signature and a novel nomogram for SCZ but also provided new insights into the subtypes of SCZ. These findings may pave the way for personalized diagnosis and treatment strategies for SCZ patients. Show less
Precise toxicological mechanism of atherosclerosis (AS) induced by environmental hazardous substance nicotine exposure remains unclear, impeding its prevention strategies and antagonist development. A Show more
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
This study employed a person-centered approach to identify latent profiles of academic burnout among Chinese university students and to examine the associations between academic burnout profiles and s Show more
This study employed a person-centered approach to identify latent profiles of academic burnout among Chinese university students and to examine the associations between academic burnout profiles and smartphone addiction, sleep quality, and mindfulness. A sample of 2,948 Chinese university students was recruited to complete measures of academic burnout, smartphone addiction, sleep quality, and mindfulness. Latent profile analysis (LPA) was used to identify distinct burnout profiles, and multinomial logistic regression was used to analyze factors associated with profile membership. Three distinct profiles of academic burnout were identified: a Low Burnout profile (18.15%), a Medium Burnout profile (50.88%), and a High Burnout profile (30.97%). The profiles differed significantly on all correlates, with the high burnout group exhibiting the most severe smartphone addiction, the poorest sleep quality, and the lowest mindfulness. Regression analysis revealed that higher smartphone addiction and poorer sleep quality were significantly associated with membership in the Medium and High Burnout profiles relative to the Low Burnout profile, whereas higher mindfulness was significantly associated with lower likelihood of belonging to higher burnout profiles. Academic burnout among Chinese university students is a heterogeneous experience, with a majority falling into an at-risk or intermediate state. Smartphone addiction, poor sleep, and low mindfulness are associated with higher burnout risk. These findings highlight the need for universities to develop targeted, profile-based interventions to provide precise and effective mental health support. However, due to the cross-sectional design, causal relationships cannot be inferred. Show less
Improved internet access has exposed rural adolescents in China to a greater risk of internet addiction. However, existing studies seldom examine the relationship between dynamic changes in internet a Show more
Improved internet access has exposed rural adolescents in China to a greater risk of internet addiction. However, existing studies seldom examine the relationship between dynamic changes in internet addiction and psychosocial maladjustment. This study aims to explore the transition patterns of internet addiction and its associations with emotional and interpersonal problems over time. A one-year longitudinal survey was conducted among 782 middle school students in rural China. Latent Profile Analysis (LPA) was conducted to identify internet addiction profiles at two time points. Latent Profile Transition Analysis (LPTA) was then used to examine the transition patterns between profiles over time. Subsequently, statistical analyses were conducted to explore how these transitions were associated with emotional and interpersonal problems. Three profiles of internet addiction were identified: minimal-internet addiction, low-internet addiction, and high-internet addiction. Based on LPTA, most adolescents with higher internet addiction at T1 shifted to lower-severity profiles over time (high → minimal: 35.3%; low → minimal: 39.8%; high → low: 33.3%), while some with initially lower levels transitioned to more severe profiles (minimal → high: 6.9%; low → high: 12.2%; minimal → low: 25.7%). Transition into higher addiction profiles predicted increased depression, anxiety, and poorer relationships with parents, peers, and teachers. Conversely, reductions in addiction were linked to improved depressive symptoms. Changes in internet addiction have an impact on adolescent psychosocial maladjustment. Early detection and flexible interventions are essential in rural settings. Show less
The choroid plexus (CP), known for producing cerebrospinal fluid, is increasingly implicated in the pathogenesis of Alzheimer's disease (AD). Neuroimaging studies document structural CP alterations in Show more
The choroid plexus (CP), known for producing cerebrospinal fluid, is increasingly implicated in the pathogenesis of Alzheimer's disease (AD). Neuroimaging studies document structural CP alterations in aging and AD. One such alteration, calcium deposition, increases with age and is typically considered benign, though the mechanism and clinical significance of CP calcification remain uncertain. Given established association between peripheral vascular calcification and cardiovascular risk, we hypothesized that the volume of calcium within CP would correlate with systemic cardiovascular health. Based on prior findings of APOEε4-specific associations between CP calcium and neurodegeneration, participants were stratified by APOEε4 status, a strong genetic risk factor for AD also implicated in cardiovascular disease. In this retrospective analysis of 105 adults (mean age 58.9 years; 39 APOEε4+), we examined whether CP calcium correlates with cardiovascular risk in cognitively normal adults. CP calcium was quantified using a previously validated MRI-CT method. Spearman correlations assessed the association of CP calcium and Framingham Cardiovascular Risk Score (FCRS), as well as individual cardiovascular risk factors. Overall, CP calcium was not associated with FCRS. Among APOEε4- subjects, CP calcium correlated positively with FCRS ( Show less
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction that is closely associated with cholinergic system damage. Estrogen deficiency is a well-est Show more
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction that is closely associated with cholinergic system damage. Estrogen deficiency is a well-established risk factor for AD in women. Osthole (OST), a phytoestrogen with mild, bidirectional regulatory properties, has been proposed as a potential estrogen replacement. This study aimed to investigate the mechanisms by which OST ameliorates cognitive impairment. Cognitive deficits were induced in female Sprague-Dawley rats by bilateral ovariectomy (OVX), and OST was subsequently administered by oral gavage. Behavioral tests revealed that OST significantly improved learning and memory and reduced anxiety-like and depression-like behaviors in OVX rats. H&E staining and Nissl staining demonstrated that OST reversed neuronal damage in the hippocampus and cortex. Western blotting, ELISA, and immunofluorescence staining indicated that OST treatment restored the estrogen-cholinergic-NGF axis: E Show less
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on Show more
Fat deposition plays a crucial role in regulating the production performance and meat quality of broilers. Although the heterogeneity of mammalian adipocytes has been extensively studied, research on the molecular mechanisms underlying differences in lipid droplet accumulation in avian adipocytes remains limited. This study confirmed a significant positive correlation (R Show less
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and is difficult to distinguish from benign pulmonary nodules (BPNs), particularly at early stages. Extracellular vesicles (EVs) re Show more
Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer and is difficult to distinguish from benign pulmonary nodules (BPNs), particularly at early stages. Extracellular vesicles (EVs) represent a promising source of biomarkers for the diagnosis of malignant pulmonary nodules. This study aimed to identify robust and clinically relevant EV-based protein biomarkers via isolation with EXODUS, a system that enables efficient direct capture of plasma EVs, followed by data-independent acquisition mass spectrometry (DIA-MS) for in-depth proteomic profiling. A total of 1383 proteins were identified from the plasma EVs obtained from 25 individuals (10 BPN and 15 early stage LUAD), while dysregulated protein signatures were revealed through differential expression analysis. Machine learning algorithms incorporating demographic variables, imaging features, EV protein profiles, and conventional tumor markers were applied to select diagnostic candidates. Random forest analysis revealed two upregulated proteins, NTN3 and APOA4, as promising biomarkers. Subsequently, their diagnostic performance and net clinical benefits were validated in an independent EV cohort (6 LUAD and 6 BPN) using ELISAs and decision curve analysis. In summary, we present an integrated pipeline that combines EXODUS-based isolation, DIA-MS, and machine learning to detect markers from plasma EVs for distinguishing early stage lung cancer from benign nodules. Show less
High-dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variant Show more
High-dose methotrexate for pediatric cancer treatment is frequently associated with mucositis, which can lead to delayed or discontinued treatment and impact survival. While individual genetic variants have been implicated, the cumulative impact of genetic variation within relevant biological pathways remains unexplored. We evaluated single nucleotide polymorphisms across 18 pathways previously identified as relevant to mucositis in 278 pediatric patients with acute lymphoblastic leukemia from six academic health centers across Canada. Pathway enrichment was assessed using the Joint Association of Genetic variants tool, and a predictive model was developed using XGBoost, a supervised machine learning algorithm based on gradient-boosted decision trees. Pathway enrichment identified significant associations in IL6 (P = 0.04) and WNT/β-catenin (P = 0.048) signaling pathways. The predictive model (area under the curve [AUC] = 0.76) highlighted single nucleotide polymorphisms associated with inflammation- and mucosa-related genes, including PRKCD, IL17B, MAST3, and CAPN9, with both risk and protective effects. Model performance dropped by 0.15 in AUC (from 0.76 to 0.61) after removing single nucleotide polymorphism features, underscoring their predictive value. This pathway-informed approach identifies genetic contributors to methotrexate-induced mucositis and supports polygenic risk prediction. Our findings provide a foundation for individualized toxicity risk profiling and suggest potential therapeutic targets to mitigate treatment-limiting mucositis in pediatric oncology. Show less
Current infant formulas lack the native multilayer structure of breast milk fat globule membrane (MFGM), impacting lipid digestion. In this study, the inner layer material and concentration of the bio Show more
Current infant formulas lack the native multilayer structure of breast milk fat globule membrane (MFGM), impacting lipid digestion. In this study, the inner layer material and concentration of the biomimetic fat globule membrane were optimized by comparing particle size, Zeta-potential and interface protein load. It was found that compared with sodium caseinate (CN) and whey protein (WP), when the lactoferrin (LF) concentration was 2 %, the particle size was lower (277.85 ± 6.15 nm) and Zeta-potential value was higher (19.67 ± 1.27 mv). Using milk phospholipid (MPL) as the outer layer material, when the MPL concentration was 2 %, the emulsion had a smaller particle size (291.33 ± 1.15 nm) and a better stability (10.22 ± 0.62 %). Therefore, the biomimetic multilayer membrane was constructed by electrostatic layer-by-layer deposition of 2 % LF and 2 % MPL. Combining Fluorescence and Fourier transform infrared spectroscopy (FTIR), the interaction between LF and MPL molecules in the LF-MPL multilayer structure is primarily a spontaneous, endothermic process driven by hydrophobic forces, exhibited superior stability (except thermal stability) than LF monolayer membrane. The results of in vitro digestion showed that compared with LF, WP and WP-MPL emulsions, LF-MPL emulsions had the highest free fatty acid (FFA) release rate of 69.97 %. LF-MPL enhanced gastric stability and promoted intestinal lipolysis and improved the degree of lipid digestion. In addition, LF-MPL promoted the absorption and utilization of triglyceride (TAG) in cells and animals, and secretion and upregulated lipid absorption genes (FATP4, DGAT1, APOB, APOA4, MTTP). These findings demonstrate that biomimetic LF-MPL multilayers improve lipid digestion, absorption, and bioavailability, providing a theoretical basis for designing more breast milk-like infant formulas. Show less
Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up. We retrospectively Show more
Long-term antigen-specific data in PMN among Chinese populations remain limited. This study evaluated six target antigens and their clinical significance during extended follow-up. We retrospectively analyzed 132 treatment-naïve PMN patients diagnosed by biopsy (2010-2018) and followed for a median of 62.9 months. Renal tissue expression of PLA2R, THSD7A, NELL-1, PCDH7, EXT1, and EXT2 was assessed by immunohistochemistry, and serum anti-PLA2R antibodies were measured by ELISA. Associations between antigen profiles and 5-year outcomes (remission, renal survival, malignancy) were evaluated. PLA2R was the predominant antigen (84.1%), followed by THSD7A (5.3%) and NELL-1 (0.76%); no PCDH7, EXT1, or EXT2 positivity was detected. PLA2R-negative patients were more often female (71.4% vs. 36.0%, This >5-year Chinese PMN cohort provides the first comprehensive analysis of six target antigens. PLA2R remains predominant, while PLA2R-negative patients distinct immunopathologic features yet favorable long-term outcomes. A population-specific anti-PLA2R cutoff showed good diagnostic performance for predicting tissue antigen deposition. Rare antigens were infrequent and their malignancy associations require cautious interpretation. These findings provide long-term antigen-specific data supporting antigen-guided, population-adapted precision management of PMN. Show less
Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating Show more
Hippocampal neuroinflammation (HNF) is a key pathological feature in neurodegenerative disorders. Milk-derived exosomes, as bioactive extracellular vesicles, have underexplored potential in regulating brain neuroinflammatory responses. This study aimed to characterize desert milk exosomes (D-Exo) and investigate their neuroprotective and anti-neuroinflammatory effects in LPS-induced HNF mice model and an LPS-stimulated BV2 microglia. Exosomes were isolated from desert and non-desert milk (ND-Exo) for proteomic analysis. After pretreating BV2 cells with exosomes and stimulating with LPS, their inflammatory responses and polarization were assessed by RT-PCR. Balb/c mice were orally gavaged with D-Exo or 0.9% NaCl for 28 days before LPS injection. Cognitive function was assessed via behavioral tests, with microglial/astrocyte activation analyzed by immunofluorescence. D-Exo exhibited superior stability and a unique proteomic profile enriched with proteins linked to neuroinflammation and blood-brain barrier (BBB) integrity, notably within the AMPK signaling pathway. In vitro, D-Exo shifted LPS-stimulated microglia from the M1 to the M2 phenotype. In vivo, it alleviated HNF and cognitive decline, reduced Aβ D-Exo is enriched with specific proteins, attenuates neuroinflammation and cognitive decline by regulating microglial M1/M2 polarization and AMPK pathway, highlighting its preventive potential. Show less
As a complex physiological and psychological phenomenon, pain has a wide impact on the quality of life of patients. Chronic pain represents one of the most challenging public health issues, and ensuri Show more
As a complex physiological and psychological phenomenon, pain has a wide impact on the quality of life of patients. Chronic pain represents one of the most challenging public health issues, and ensuring effective pain management is not only a fundamental right of individuals but also a sacred duty of healthcare providers. This review focuses on recent advancements (within the past five years) in understanding how electroacupuncture (EA) alleviates pain-related affective disorders, such as anxiety and depression. By integrating findings from clinical trials and mechanistic studies, we highlight three key mechanisms: (1)Brain functional regulation: EA modulates brain regions (e.g., prefrontal cortex, insula, thalamus) and networks (default mode network, salience network) via functional magnetic resonance imaging (fMRI)-observed functional connectivity changes. (2)Neurotransmitter and receptor modulation: EA regulates pain and emotions by altering BDNF, β-endorphin, TRPV1, NMDARs, and P2Y12 receptor signaling, supported by studies on chronic pain and depression models. (3)Immune factor adjustment: EA reduces neuroinflammation by targeting TLR4/NF-κB pathways and pro-inflammatory cytokines (IL-1β, TNF-α), improving pain-related affective disorders. Clinical and preclinical evidence demonstrates EA's safety, efficacy, and multi-target effects, however, optimal treatment parameters and individualized strategies require further investigation. Future research should combine multi-omics, large-scale multi-center clinical studies , and precision medicine approaches to deepen understanding of EA's mechanisms and clinical applications. Show less
This study was conducted to investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis (HS) combined with familial chylomicronemia syndrome (FCS), identify t Show more
This study was conducted to investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis (HS) combined with familial chylomicronemia syndrome (FCS), identify the pathogenic cause, and provide a basis for the clinical diagnosis, treatment, and genetic counseling of affected children. Clinical data were collected from family members. High-throughput sequencing was performed to identify pathogenic variants in genes associated with HS and FCS in the proband. Suspected pathogenic mutations were confirmed in family members via PCR-Sanger sequencing. Bioinformatics analysis and three-dimensional protein structure prediction were also conducted. The proband presented with severe anemia, splenomegaly, and jaundice. Genetic testing revealed a heterozygous mutation, c.6005G>A (p.Trp2002*), in the spectrin beta chain ( The heterozygous mutations Show less
Guangming Li, Yi Jin, Xiaowei Yuan+4 more · 2026 · Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · Elsevier · added 2026-04-24
Dibutyl phthalate (DBP) is a widely distributed endocrine-disrupting chemical with potential carcinogenic properties, yet its role in head and neck squamous cell carcinoma (HNSC) remains unclear. Here Show more
Dibutyl phthalate (DBP) is a widely distributed endocrine-disrupting chemical with potential carcinogenic properties, yet its role in head and neck squamous cell carcinoma (HNSC) remains unclear. Here, we applied an integrative framework combining network toxicology, Mendelian randomization (MR), multi-omics analyses, molecular docking, molecular dynamics simulations, and in vitro experiments to elucidate the mechanisms underlying DBP-associated HNSC. Lipoprotein lipase (LPL) was identified as the sole overlapping gene between DBP-related targets and HNSC-associated genes. MR analysis supported a potential causal relationship between LPL and HNSC susceptibility. Expression profiling demonstrated tissue- and cell type-specific patterns of LPL and its dysregulation in HNSC, with associations to tumor stage and prognosis. Genomic analyses revealed that LPL alterations were infrequent and mainly driven by copy number loss. LPL expression positively correlated with immune and stromal infiltration. Enrichment analyses implicated immune regulation and PI3K-AKT signaling. Molecular simulations showed stable DBP-LPL binding. Functionally, DBP promoted SCC9 proliferation and reduced LPL expression, and was associated with transcriptional changes in PI3K-AKT-mTOR-related genes, whereas LPL restoration mitigated these effects. These findings reveal a novel DBP-LPL axis in HNSC. Show less
This study aims to examine the health characteristics of female sex workers (FSWs) in entertainment venues and to investigate the relationship between these characteristics and sleep quality. This stu Show more
This study aims to examine the health characteristics of female sex workers (FSWs) in entertainment venues and to investigate the relationship between these characteristics and sleep quality. This study employed a cross-sectional design and was conducted from January to April 2024 in Wuhan, China. Participants were FSWs recruited through snowball sampling from entertainment venues, including hotels, restaurants, nightclubs, karaoke bars and dance halls. Data were collected via structured questionnaires covering sociodemographic information, work experience, psychological stress, health status, sleep quality and circadian rhythms. Latent profile analysis (LPA) was employed to identify health characteristic profiles among FSWs, and multivariate logistic regression was used to examine the associations between these profiles and sleep quality. Among the 1,036 FSWs surveyed, 45.1% had poor sleep quality. LPA classified FSWs’ health characteristics into three profiles: the high overall functioning group, the lower physical–emotional functioning group and the lower psychosocial functioning group. Multivariate logistic regression analysis showed that FSWs in the lower physical–emotional functioning group had higher odds of poor sleep quality (OR = 2.184) compared with those in the high overall functioning group. FSWs in the lower psychosocial functioning group had substantially higher odds of poor sleep quality (OR = 7.755) than that in the high overall functioning group. FSWs demonstrate substantial heterogeneity in health characteristics and exhibit lower overall sleep quality compared with the general population. Psychological and physiological factors are major influencing factors for their sleep quality, suggesting the importance of prioritising mental and physical health in this population. Show less
Coronary artery disease (CAD) remains a leading cause of mortality worldwide, with substantial unmet therapeutic needs. This study aimed to identify and prioritize genetically supported therapeutic ta Show more
Coronary artery disease (CAD) remains a leading cause of mortality worldwide, with substantial unmet therapeutic needs. This study aimed to identify and prioritize genetically supported therapeutic targets for CAD using Mendelian randomization (MR). We implemented a two-sample MR framework to infer the causal effects of blood druggable cis-expression quantitative trait loci (cis-eQTLs) on CAD. To consolidate MR findings, we applied Steiger filtering, Bayesian colocalization, and multiple sensitivity analyses. Mediation and phenomewide MR analyses were employed to investigate potential mechanisms and on-target effects of prioritized druggable genes. We identified 66 causal druggable genes associated with CAD in European populations (false discovery rate < 0.001). Among these, ERP29 (odds ratio [OR] = 1.311; 95% confidence interval [CI]: 1.176-1.460), MCL1 (OR = 0.877; 95% CI: 0.840-0.915), TNXB (OR = 1.183; 95% CI: 1.102-1.269), DAGLB, FES, and TRPM4 colocalized with CAD (posterior probability for colocalization > 0.8). The associations for ERP29, MCL1, and TNXB were replicated in an East Asian cohort. Protein-protein interaction network analysis highlighted MAPK3 and TNF as prioritized druggable targets at the protein level. Mediation analysis indicated that body mass index, triglycerides, blood pressure, and atrial fibrillation partially mediate the association between MAPK3 and CAD. Phenome-wide MR analysis further suggested additional beneficial effects of targeting MAPK3 and TNF on diabetes mellitus, obesity, hypertension, unstable angina, myocardial infarction, angina pectoris, coronary atherosclerosis, ischemic heart disease, and disorders of lipoid metabolism. This druggable genome-wide MR study not only corroborated the targets of FDA-approved CAD medications (e.g., FGFR1, MAPK3, NEU1) but also uncovered several novel genes, such as ERP29, MCL1, TNXB, DAGLB, FES, and TRPM4, implicating mechanisms related to blood pressure, lipid metabolism, and additional beneficial effects on endocrine/cardiometabolic traits and circulatory system disorders. Further exploration is imperative to explore their feasibility and generalizability. We identified circulating ERP29, MCL1, TNXB, DAGLB, FES, TRPM4, MAPK3, and TNF as promising, genetically supported druggable targets for CAD treatment. Notably, MAPK3 and TNF demonstrated strong protein-level interactions and close associations with cardiometabolic disorders. Show less
Lecanemab is an anti-Aβ antibody approved in China for mild cognitive impairment (MCI) and mild dementia. Real-world application requires comprehensive assessment beyond MMSE scores, considering facto Show more
Lecanemab is an anti-Aβ antibody approved in China for mild cognitive impairment (MCI) and mild dementia. Real-world application requires comprehensive assessment beyond MMSE scores, considering factors like ARIA risk. This single-center, real-world study aims to evaluate its efficacy in an expanded population, observe biomarker changes, and assess its safety profile in clinical practice. We recruited adults aged 40-90 with early AD from the PUMCH Dementia Cohort. A total of 42 patients received lecanemab treatment, of whom 29 completed the 6-month treatment evaluation. Participants had confirmed amyloid and tau pathology and met clinical criteria (CDR ≤ 1, CDR-SB ≤ 8and MMSE ≥ 18). Comprehensive assessments included neuropsychological testing, CSF and plasma biomarkers (Lumipulse G1200), multi-sequence 3T MRI (volumetric and ALPS index analysis), and amyloid/tau PET imaging (Centiloid quantification). All were monitored for adverse reactions. Matched control groups (matched for sex, age, APOE genotype, disease severity, and baseline therapy) were established for comparison of longitudinally changes in cognitive function, daily living ability and structure MRI. Treatment was effective even for patients with lower MMSE scores but still classified as having mild dementia by CDR. A significant median Centiloid reduction of 30.9 was observed, with a 24.1% amyloid PET negativity rate after six months. While scores on cognitive and functional scales (CDR-SB, ADL) significantly worsened, indicating disease progression, the rate of progression was significantly slower compared to the control group. Structural MRI showed significant volume reduction in multiple brain regions and increased ventricular volume post-treatment, with no statistically significant change in the ALPS value. The rate of brain volume reduction is faster than that in the control group. Plasma biomarker dynamics (Aβ This study confirms the clinical efficacy, biomarker changes, and safety profile of lecanemab treatment over a 6-month period, demonstrating its positive therapeutic value and a favorable safety profile in the Chinese population with AD. Show less
The apolipoprotein E ε4 (APOE ε4) allele is a major genetic risk factor for Alzheimer's disease, but its relevance to cognition in intracranial atherosclerosis (ICAS) remains unclear. We investigated Show more
The apolipoprotein E ε4 (APOE ε4) allele is a major genetic risk factor for Alzheimer's disease, but its relevance to cognition in intracranial atherosclerosis (ICAS) remains unclear. We investigated the association between APOE ε4 and cognition in ICAS. Baseline data from a multicenter cohort were analyzed. Patients with radiologically confirmed ICAS underwent APOE genotyping, plasma biomarker assays, magnetic resonance imaging assessment of cerebral small vessel disease (CSVD) and brain atrophy, and standardized cognitive testing. Among 409 patients (mean age 60 years, 55% male), 16% carried APOE ε4. Carriers showed more frequent cognitive impairment (63% vs 48%), greater stenosis burden, and lower plasma amyloid beta (Aβ)42/40 ratios, whereas other Alzheimer's biomarkers, CSVD burden, and atrophy scores showed no difference. After adjustment, APOE ε4remained associated with cognitive impairment (odds ratio [OR] 1.86). The association was pronounced in women (OR 4.43) but absent in men. APOE ε4 is linked to cognitive impairment in ICAS, particularly in women, through mechanisms beyond Alzheimer's pathology. In patients with ICAS, cognitive impairment was more prevalent in carriers than in non-carriers. Carriers showed greater stenosis burden and lower plasma Aβ42/40 ratios. After full adjustment (stroke, CSVD, and AD biomarkers), APOE ε4 remained associated with cognitive impairment. Female carriers had substantially higher odds of cognitive impairment. Show less
This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidi Show more
This study aims to demonstrate the effect of toadflax (bufalin) on erlotinib resistance in nonsmall cell lung cancer (NSCLC) by inhibiting the fibroblast growth factor receptor (FGFR). The microfluidic mobility transferase and caliper mobility-shift assays were employed to detect the FGFR inhibition by bufalin and the binding reversibility. Further, the inhibitory effects of bufalin were determined in HCC827 and HCC827/ER cells in vitro , investigating relative FGFR overexpression by quantitative reverse transcriptase-PCR (RT-qPCR) and FGFR downstream proteins, that is, FGFR substrate 2 (FRS2), extracellular signal-regulated kinase (ERK), and S6 by western blot analysis. Finally, HCC827/ER-inoculated xenograft tumors were constructed to observe the effects of bufalin and bufalin + erlotinib intervention on tumor growth. Bufalin inhibited FGFR by reversibly binding to FGFR1. In addition, the western blot analysis indicated a significant reduction in the expression levels of FGFR, FRS2, ERK, and S6 proteins in HCC827 and HCC827/ER cells, increasing the expression levels of apoptotic caspase-3 and poly-(ADP-ribose) polymerase proteins. Bufalin + erlotinib combination significantly inhibited the apoptosis of HCC827/ER cells and subsequent tumor growth in vivo . In addition, FGFR overexpression significantly reversed the sensitivity of bufalin to HCC827/ER cells, promoting the value-addition of HCC827/ER cells. Further, bufalin + erlotinib significantly reduced the growth of erlotinib-resistant HCC827/ER tumors, induced apoptosis, and inhibited the expression of FGFR and p-ERK proteins. These findings indicated that bufalin could reverse the erlotinib resistance in NSCLC by inhibiting the FGFR expression. Show less
This network meta-analysis (NMA) evaluated four novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for hypercholesterolemia management, comparing their lipid-lowering ef Show more
This network meta-analysis (NMA) evaluated four novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies for hypercholesterolemia management, comparing their lipid-lowering efficacy and safety. We systematically identified randomized controlled trials employing the frequentist NMA method to assess reductions in low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp[a]), alongside treatment-emergent adverse events (TEAEs) and serious TEAEs. A total of eight trials with 3,975 Chinese patients were included. Ongericimab 150 mg every 2 weeks (Q2W) ranked first in all efficacy outcomes, demonstrating pronounced effects in LDL-C, ApoB, and Lp(a) reduction versus placebo, with mean differences of -74.21% (95% confidence interval [CI]: -79.69% to -68.73%), -64.36% (95% CI: -68.58% to -60.13%), and -50.93% (95% CI: -56.24% to -45.61%), respectively. All interventions exhibited safety profiles comparable with placebo, with no significant differences in TEAEs or serious TEAEs incidence. The analyses suggested that a portion of the evidence base was robust and reliable. These findings positioned ongericimab 150 mg Q2W as a clinically optimal PCSK9 inhibitor with robust lipid-lowering capacity. The results highlight the potential of next-generation PCSK9 monoclonal antibodies, particularly in East Asian populations, while underscoring the need for large-scale multinational trials to validate ethnic-specific responses. Show less