Volatile fatty acids (VFAs) provide more than 70% of the energy source for the ruminants. Understanding the host-microbiota regulation of VFAs production and utilization is highly important for optimi Show more
Volatile fatty acids (VFAs) provide more than 70% of the energy source for the ruminants. Understanding the host-microbiota regulation of VFAs production and utilization is highly important for optimizing the feed energy utilization efficiency of ruminants. Here, we conducted whole-genome resequencing, rumen transcriptome sequencing, 16S rRNA gene amplicon sequencing, and VFA concentration determination in 530 Holstein bulls. We treated VFA concentrations as complex traits to perform multi-omics association analyses. The host genetics, rumen microbiota, and rumen expressed genes, on average, explained 23%, 58%, and 61% of the variations in VFAs with the same diet, respectively. We found that the rumen microbial composition and community structure differed significantly between the high and low VFA individuals. We further identified 11 microbes with potential causal relationships with rumen VFAs via the Mendelian randomization method, among which Bacteroidales_RF16_group, Prevotella, Clostridia_UCG-014, and [Eubacterium]_ventriosum_group were positively correlated with acetic acid, propionic acid, and butyric acid. Conversely, rumen epithelial genes involved in fatty acid β-oxidation (e.g., HSD17B4, ACADVL, ACADL, CPT1A, and ANGPTL4) were negatively correlated with the main VFAs and VFA-producing bacteria. These candidate microbes and genes suggest that the host-microbe coregulating mechanism facilitates the efficient production and utilization of rumen VFAs in ruminants. Our study provides a comprehensive perspective on the complex dynamic regulatory patterns of rumen VFAs, highlighting the crucial role of host-microbe interactions in optimizing the feed utilization of ruminants. Show less
Aging-related cognitive decline is a major concern in aging societies. Theobromine (TB), a cacao-derived methylxanthine, exerts neuroprotective effects through anti-inflammatory, antioxidant, and neur Show more
Aging-related cognitive decline is a major concern in aging societies. Theobromine (TB), a cacao-derived methylxanthine, exerts neuroprotective effects through anti-inflammatory, antioxidant, and neurotrophic mechanisms; however, its efficacy in aging models remains unclear. This study investigated the mechanisms underlying neuroprotective effects of chronic TB administration in senescence-accelerated mouse prone 8 (SAMP8), a model of age-related memory impairment. SAMP8 and SAMR1 mice were fed either a control diet or a diet supplemented with 0.05% TB for 50 d. Cognitive performance was evaluated by the novel object recognition (NOR) test. Neurotrophic factors (BDNF and NT-3), synaptic proteins (PSD95 and synaptophysin), and plasticity-related signaling molecules (phosphorylated CREB and TrkB) were analyzed in the prefrontal cortex and hippocampus. Inflammatory cytokines, lipid peroxides, and antioxidant enzymes were quantified. Molecular docking was used to assess TB's interaction with phosphodiesterase (PDE) enzymes. TB improved short-term memory in SAMP8, increasing discrimination index in the NOR test. This was accompanied by increased BDNF, NT-3, PSD95, and synaptophysin levels and enhanced CREB and TrkB phosphorylation. Furthermore, TB lowered the levels of pro-inflammatory cytokines (IL-1β, TNF-α) and phosphorylated NF-κB, reduced lipid peroxidation, and increased the levels of antioxidant markers (HO-1, GSH). These effects were minimal in SAMR1. No adverse effects on body weight or blood parameters were observed. Molecular docking indicated that TB binds to PDE enzymes with weaker inhibitory activity than selective inhibitors. TB enhances short-term memory and synaptic function in aged mice via neurotrophic, antioxidant, and anti-inflammatory mechanisms, supporting its potential as a safe dietary intervention for age-related cognitive decline. Show less
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson' Show more
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival of dopaminergic neurons. Clinical studies have suggested that serum BDNF levels are reduced in patients with Parkinson's disease (PD). However, no study has investigated peripheral BDNF levels and BDNF Val66Met polymorphism in the prodromal stage of PD and their relationship with disease conversion. In total, 120 patients with video-polysomnography confirmed isolated REM sleep behavior disorder (iRBD) and 120 healthy controls (HCs) were enrolled. Genetic analyses were performed, and plasma levels of BDNF were measured. All patients with iRBD underwent comprehensive clinical testing, and 107 iRBD patients were prospectively followed up. Plasma BDNF levels were significantly lower in the iRBD group than in HCs (18,878.85 pg/mL vs. 24,649.85 pg/mL, p = 0.002), but no differences were observed in BDNF Val66Met carrier rates between the two groups. Plasma BDNF levels did not differ significantly between BDNF Val66Met carriers and noncarriers. Notably, higher plasma BDNF levels were associated with an increased risk of short-term disease conversion (hazard ratio = 3.418, 95% CI: 1.520-7.684, p = 0.003), whereas BDNF Val66Met carrier rates showed no such association. Our findings suggest that plasma BDNF is significantly associated with iRBD and may likely serve as a prognostic biomarker for the development of neurodegenerative disease. However, the BDNF Val66Met polymorphism may not be involved in the pathogenesis of iRBD as well as phenoconversion in the studied population. Show less
Vascular smooth muscle cell senescence contributes critically to vascular remodeling and atherosclerosis, with mitochondrial dysfunction and impaired mitophagy recognized as major contributors. SRC, a Show more
Vascular smooth muscle cell senescence contributes critically to vascular remodeling and atherosclerosis, with mitochondrial dysfunction and impaired mitophagy recognized as major contributors. SRC, a stress-responsive tyrosine kinase, has been linked to aging, yet its role in vascular aging remains unclear. Here, we examined the role of SRC in regulating autophagy/mitophagy using in vitro and in vivo models. An accelerated vascular aging model was established using a high-fat diet and streptozotocin injection in ApoE Show less
Xi-Yu Zhao, Zhen-Qi Wu, Tian-Yu Zhang+4 more · 2026 · Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica · added 2026-04-24
Attention deficit hyperactivity disorder(ADHD), a common neurodevelopmental disorder in children, is characterized by inattention, hyperactivity, and impulsivity. Epidemiological surveys show that the Show more
Attention deficit hyperactivity disorder(ADHD), a common neurodevelopmental disorder in children, is characterized by inattention, hyperactivity, and impulsivity. Epidemiological surveys show that the prevalence of ADHD in children is gradually increasing worldwide, and it is the most common childhood mental disorder in China. Because of the complex clinical symptoms, multiple co-morbidities, and unknown etiology, ADHD has far-reaching negative impacts on individuals, families, and the society. Behavioral interventions, as a pillar in the management of ADHD, play a targeted role in improving children's social functioning, with significant benefits supported by evidence. However, they are constrained by uneven resources, poor compliance, and insufficient continuity, Western medicine has multiple adverse effects and unclear long-term effects in the treatment of ADHD despite the definite efficacy. Accordingly, there is an urgent need to find safe and effective therapies suitable for children. With a holistic view and treatment based on syndrome differentiation, traditional Chinese medicine(TCM) has significant advantages in treating ADHD via multiple targets, which involves dopamine(DA), norepinephrine(NE), 5-hydroxytryptamine(5-HT), cyclic adenosine monophosphate(cAMP), brain-derived neurotrophic factor(BDNF) and other signaling pathways. Through these pathways, TCM can treat ADHD through the regulation of neurotransmitters, enhancement of prefrontal and striatal functions, enhancement of neuronal protection, attenuation of neuroinflammation, and reduction of neuronal apoptosis. However, a systematic study remains to be conducted. This paper summarizes the signaling pathways related to the treatment of ADHD by TCM in the past two decades, aiming to provide reference for delving into the mechanism and exploring effective TCM prescriptions for ADHD in children and to give full play to the advantages of the efficacy and characteristics of TCM. Show less
This study aims to evaluate the association between multiple lipid indices and coronary collateral circulation (CCC) in patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI) Show more
This study aims to evaluate the association between multiple lipid indices and coronary collateral circulation (CCC) in patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI). This was a cross-sectional retrospective study involving 421 patients with STEMI who underwent coronary angiography between January 2022 and December 2024. Participants were categorized into a poor CCC group (Rentrop grade 0-1) and a good CCC group (Rentrop grade 2-3) according to Rentrop grading criteria. The following lipid parameters were evaluated as both continuous and categorical variables: total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (ApoB), apolipoprotein A-I (ApoA-I), non-HDL-C/HDL-C, ApoB/ApoA-I, atherogenic index of plasma (AIP), and lipoprotein composite index (LCI). The associations between these lipid indices and CCC status were assessed using multivariate logistic regression and receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis revealed that higher HDL-C quartiles were significantly associated with reduced odds of poor CCC (odds ratio [OR]: 0.544, 95% confidence interval [CI]: 0.351-0.771, P < 0.05), whereas elevated LDL-C (OR: 29.299, 95% CI: 3.562-240.976, P < 0.05), non-HDL-C (OR: 50.140, 95% CI: 5.408-464.834, P < 0.01), and non-HDL-C/HDL-C (OR: 4.510, 95% CI: 1.186-25.368, P < 0.05) quartiles were significantly associated with increased odds of poor CCC. Receiver operating characteristic (ROC) curve analysis demonstrated that LDL-C (cutoff: 3.265, AUC: 0.647, 95% CI: 0.573-0.721, P < 0.001), non-HDL-C (cutoff: 2.735, AUC: 0.752, 95% CI: 0.688-0.816, P < 0.001), and non-HDL-C/HDL-C (cutoff: 2.393, AUC: 0.686, 95% CI: 0.611-0.761, P < 0.001) exhibited favorable predictive performance for poor CCC. Stratification analysis showed that the highest prevalence of poor CCC was observed in patients with concurrently elevated levels of LDL-C, non-HDL-C, and non-HDL-C/HDL-C. Several lipid indices-including LDL-C, non-HDL-C, and the non-HDL-C/HDL-C ratio-are significantly associated with impaired CCC in patients with STEMI. Notably, non-HDL-C exhibits the strongest association with CCC dyscrasia and therefore warrants early clinical attention. Show less
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the ef Show more
Endothelial cells under oxidative stress and inflammation are vital contributors to the progression of atherosclerosis. Although Orientin possesses antioxidant and anti-inflammatory activities, the effects of Orientin on oxidized low-density lipoprotein and high glucose (ox-LDL/HG)-triggered endothelial cell injury and diabetes-accelerated atherosclerosis remain unclear. ApoE Show less
Validate the clinical utility of exosome cargo (miRNAs/proteins) and NLRP3/BDNF as key regulatory molecules for acupuncture-mediated spinal cord injury (SCI) recovery. From the establishment of the da Show more
Validate the clinical utility of exosome cargo (miRNAs/proteins) and NLRP3/BDNF as key regulatory molecules for acupuncture-mediated spinal cord injury (SCI) recovery. From the establishment of the database to May 2025, a literature search was conducted on PubMed, and Embase, using keywords ["exosome cargo" or "exosome"], ["acupuncture" or "acupuncture and moxibustion" or "electroacupuncture" or "EA"], ["spinal cord injury" or "SCI"], ["immune regulation"], ["inflammatory reaction"], ["neuroregeneration" or "nerve"]. Including peer-reviewed studies on human/animal models, articles that do not meet the requirements are excluded. Preclinically, MSC-exosomal miR-145-5p suppressed TLR4/NF-κB signaling, reducing spinal IL-1β by 47% in SD rats. Schwann cell-exosomal MFG-E8 activated SOCS3/STAT3, increasing M2 macrophage CD206 by 63% and raising rat BBB scores by 3.8 points; Treg-exosomal miR-2861 upregulated tight junction proteins (occludin/ZO-1) to repair the blood-spinal cord barrier. Acupuncture (EA at GV14/GV4) upregulated spinal BDNF by 72% and NGF by 58% via Wnt/β-catenin, while EA at GV6/GV9 downregulated NLRP3 by 42-58% and TNF-α by 35-47%. Clinically, EA at EX-B2 increased ASIA scores by 3.2±1.1 points (Guo et al). Besides, 5x/week EA improved ASIA vs 3x/week (+6.4 points). EA+exercise reduced MAS by 1.6-2.9 points, with outcomes correlated to peripheral NLRP3 reduction, BDNF elevation, and MBI/WISCIII increases. Exosome cargo (miR-145-5p/MFG-E8) and NLRP3/BDNF are key regulatory molecules underlying acupuncture-mediated SCI recovery. However, limitations (small RCT samples, heterogeneous acupuncture protocols, unstandardized exosome isolation) hinder translation. Future work should focus on standardized biomarker detection, exosome engineering, and large-scale clinical trials. Show less
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related deaths. Immune checkpoint inhibitors (ICIs) of programmed death-1 (PD-1)/programmed de Show more
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of cancer-related deaths. Immune checkpoint inhibitors (ICIs) of programmed death-1 (PD-1)/programmed death ligand-1 signaling induce tumor regression in some patients with NSCLC, but most patients with NSCLC exhibit resistance to ICIs therapy. NSCLC shapes the potent tumor immunosuppressive microenvironment (TIME) that underlies tumor immune tolerance and acquired resistance. Therefore, elucidating the cellular and molecular mechanisms by which NSCLC establishes and sustains the TIME is essential for developing novel strategies to overcome immune resistance and enhance the clinical benefit of ICIs. The correlation between sterile alpha motif domain and histidine-aspartate domain-containing protein 1 (SAMHD1) expression and ICIs was analyzed via immunohistochemistry. Cell migration assay was performed to assess the effect of SAMHD1 on macrophage recruitment. Multicolor flow cytometry was performed to analyze the effect of SAMHD1 knockdown on the tumor microenvironment. SAMHD1 regulation of the dual specificity phosphatase 6-extracellular regulated protein kinases 1/2 (DUSP6-ERK1/2) pathway was verified by RNA sequencing and western blotting. Here, we identify the SAMHD1 as a potential therapeutic target and a major determinant of poor response to ICIs in patients with NSCLC. Tumors with high SAMHD1 expression show resistance to anti-PD-1 antibody (αPD-1) treatment, whereas tumors with low SAMHD1 expression are highly sensitive. SAMHD1-dependent resistance to αPD-1 is characterized by increased tumor-associated macrophages (TAMs) infiltration and reduced CD8+T cell numbers. Mechanistically, SAMHD1 regulates the expression of macrophage-associated chemokines by influencing the activation of the DUSP6-ERK1/2 pathway, which contributes to TAMs aggregation within NSCLC tumors to shape an immunosuppressive microenvironment. The HIV accessory protein viral protein-x (VPX) specifically degrades SAMHD1 to promote HIV replication. Similarly, the vpx-engineered oncolytic adenovirus (oAd-vpx) targets SAMDH1 degradation to enhance oncolytic adenovirus replication and weaken the hostile immune microenvironment shaped by TAMs, thereby triggering a CD8+T-cell-dependent antitumor immune response. The combination of oAd-vpx and αPD-1 inhibits tumor growth and enhances sensitivity to ICIs in both mouse and human NSCLC. This research identifies a key mechanism of SAMHD1-driven immunosuppression and highlights its important role in oncolytic adenovirus therapy. This study provides a theoretical basis for targeting SAMHD1 as a drug therapy strategy in patients with NSCLC. Show less
In vitro maturation (IVM) is highly susceptible to influences of the culture environment, which can lead to increased intracellular reactive oxygen species (ROS) levels and thereby induce a stress res Show more
In vitro maturation (IVM) is highly susceptible to influences of the culture environment, which can lead to increased intracellular reactive oxygen species (ROS) levels and thereby induce a stress response in oocytes, ultimately reducing the developmental potential of early embryos. Brain-derived neurotrophic factor (BDNF) is an ovarian endocrine factor that can enhance the function of follicular granulosa cells and promote oocyte maturation, but the specific pathways remain unclear. We supplemented IVM cultures of sheep oocytes with BDNF and examined aspects of oocyte nuclear and cytoplasmic maturation. The addition of 50 ng/mL BDNF promoted the expansion of cumulus cells and increased the rates of first polar body extrusion, cleavage, and blastocyst formation. Compared with untreated controls, BDNF-treated oocytes had improved Ca Show less
Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat faci Show more
Facial nerve injury (FNI) is a common peripheral neuropathy that severely impairs facial function and quality of life. Qianzheng Powder (QZP) is a traditional Chinese herbal formula used to treat facial paralysis clinically, yet its neuroprotective mechanisms remain unclear. This study aims to evaluate the therapeutic effects of QZP on FNI and potential underlying mechanisms. A FNI model was established in male C57BL/6 mice by performing facial nerve crush surgery. QZP (3.51 g/kg) was administered orally once daily for 14 days post-surgery. Facial function was assessed behaviorally. Tissue samples were collected on day 21 for histological evaluation, qPCR and Western blotting. Liver and kidney safety were also assessed via H&E staining and serum biochemical markers. QZP significantly improved facial motor function from day 7 post-injury. Additionally, QZP treatment mitigated neuronal loss in the facial motor nucleus, attenuated buccinator muscle atrophy, and enhanced myelin regeneration, as evidenced by increased MPZ and MBP expression. These were consistent with the increace of the BDNF, TrkB, and QZP promotes structural and functional recovery of facial nerve following injury, likely through activation of the BDNF/TrkB/CREB axis, and demonstrates a favorable safety profile. These findings support its potential as a therapeutic adjunct in peripheral nerve repair. Show less
Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. T Show more
Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. This study aimed to observe the mechanism of EA as an adjunct therapy to escitalopram oxalate (EO) on depressed patients. This study was designed as a single-blinded, double-dummy randomized controlled trial. 61 participants were diagnosed with mild-to-moderate depression according to the International Classification of Diseases 10th Edition (ICD-10, F32) were randomly allocated to receive EA + EO placebo, EO + sham EA, or EA + EO for six weeks treatment. The clinical assessment including depression severity, quality of life (QOL) and clinical safety. Biological indicators of immune-inflammation, the brain-derived neurotrophic factor and glucocorticoid inducible genes in peripheral blood of participants were measured by using enzyme linked immunosorbent assay and real-time polymerase chain reaction respectively before and after treatment. Three interventions improved the depression severity and QOL (P < 0.05), and no inter-group difference was found in the 6th week (P > 0.05). Anxiety psychic and somatic general symptoms in the EA + EO group were improved significantly than those of the other two groups (P < 0.05). After six-week treatment of EA + EO, blood SGK1 mRNA, GILZ mRNA, and BDNF levels were increased significantly ( Show less
Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a Show more
Hypertrophic scar (HS) is a fibroproliferative disorder characterized by fibroblast hyperactivation and aberrant extracellular matrix deposition. This study identifies macrophage-derived lactate as a key mediator of fibroblast phenotypic remodeling via monocarboxylate transporter 1 (MCT1)-mediated histone H3 lysine 23 lactylation (H3K23la) in HS. Elevated lactate levels and MCT1 expression were observed in HS tissues, with macrophages in stiff mechanical microenvironments identified as the primary lactate source. Lactate influx through MCT1 upregulated H3K23la, thereby promoting transcriptional activation of profibrotic genes HEY2 and COL11A1. Mechanistically, HEY2 activated YAP1/SMAD2 signaling, while COL11A1 stabilized MCT1 to enhance lactate transport, forming a positive loop that amplified fibrosis. Fibroblast-specific Mct1 deletion or pharmacological inhibition of Mct1 in male mice reduced collagen deposition, accelerated wound healing, and attenuated scar formation. Our findings redefine the macrophage-fibroblast crosstalk in HS and establish the MCT1-H3K23la-HEY2/COL11A1 axis, particularly its self-reinforcing loop, as a novel therapeutic target. Show less
Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study dem Show more
Cerebral palsy (CP), the most prevalent pediatric motor disorder with significant cognitive comorbidity (> 50%), lacks therapies addressing both impairments in moderate-to-severe cases. This study demonstrates that human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) exert profound therapeutic effects in a rat model of moderate-to-severe CP established via bilateral carotid artery occlusion with hypoxia. Intravenously administered hUCMSC-Exos displayed sustained brain retention and significantly restored motor coordination and cognitive function. The recovery was primarily mediated through enhanced remyelination driven by promoted oligodendrocyte maturation and differentiation (elevated oligodendrocyte lineage transcription factor 2 and myelin basic protein). Concurrently, the treatment attenuated key pathological processes involving sustained neuroinflammatory responses (reduced ionized calcium-binding adapter molecule 1, tumor necrosis factor-α, and interleukin-6) while elevating brain-derived neurotrophic factor. Our findings establish hUCMSC-Exos as a promising dual-modality therapy for moderate-to-severe CP, mechanistically linked to robust remyelination and coordinated modulation of core disease mechanisms. 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
Digital technology is frequently regarded as a tool to alleviate loneliness and enhance mental health among older adults, yet its effectiveness remains contested. This study explores whether digital e Show more
Digital technology is frequently regarded as a tool to alleviate loneliness and enhance mental health among older adults, yet its effectiveness remains contested. This study explores whether digital exclusion moderates the association between loneliness and depressive, and examines symptom structure and depressive subtypes. Drawing on data form the 2018 and 2020 waves of the CHARLS (N = 13,719), we employed fixed-effect and mixed-effect models to assess the effect of loneliness on depressive and the moderating role of digital exclusion. Latent profile analysis (LPA) was used to identify symptoms subtypes, while symptom network analysis assessed centrality and network stability. Loneliness significantly predicted depressive symptoms across multiple models, demonstrating robust effects. Digital exclusion was positively associated with depressive symptoms but did not exhibit a statistically significant moderating effect on the loneliness-depression relationship (p > 0.05, Δβ ≈ 0.011). LPA identified six psychologically meaningful subtypes of depression. Symptom network analysis revealed that emotional and motivational symptoms occupied central positions within the network structure, whereas loneliness, despite its strong connections, exhibited relatively low centrality. The overall network structure remained stable over two years, with the digital access group exhibiting stronger network connectivity. This study emphasizes that digital access alone is not a universal remedy for alleviating loneliness. The psychological benefits of digital technology depend on the alignment between individual motivations, usage patterns, and broader social contexts. Future research should focus on digital usage quality and contextual adaptability of interventions, promoting a shift from customization in digital mental health intervention strategies. Show less
Current in vitro enzyme inhibition assays often involve subjective data analysis based on the researcher's experience. In this study, we developed a multi-dimensional quantitative integration platform Show more
Current in vitro enzyme inhibition assays often involve subjective data analysis based on the researcher's experience. In this study, we developed a multi-dimensional quantitative integration platform (MDQIP) that uses a model to objectively calculate and rank compound activities, addressing the limitations of traditional "experience-driven" evaluations, accelerates the screening and evaluation of potential AChE inhibitors from Red Gastrodia elata, offering a more efficient approach to drug discovery. Ultrafiltration-LC screening identified parishin A as having the most stable binding, with binding degree and recovery rates of 98.85% and 99.39%, respectively. Molecular docking revealed that parishins A and C were the strongest AChE inhibitors, exhibiting stable binding through hydrogen bonds, π-alkyl, and π-π interactions. Molecular dynamics simulations confirmed the stability of these compounds, with binding energies of -82.65 ± 4.24 and - 80.69 ± 4.19 kcal/mol. Enzyme kinetics showed that parishins A and C are mixed-type inhibitors, with IC Show less
The presence of a blood-brain barrier (BBB) prevents the delivery of most drugs to the brain. This characteristic limitation poses a major challenge to effective pharmacological treatment for numerous Show more
The presence of a blood-brain barrier (BBB) prevents the delivery of most drugs to the brain. This characteristic limitation poses a major challenge to effective pharmacological treatment for numerous neurodegenerative diseases, particularly Alzheimer's disease. Delivering small interfering RNA (siRNA) via nanoparticles represents a highly promising approach for treating Alzheimer's disease. Nevertheless, developing a safe and efficient siRNA delivery system remains challenging. To enhance brain targeting and therapeutic efficacy, we developed an siRNA nanocarrier system based on PAH-AM-PEG-ApoE (PAPA) nanoparticles (PAPA/siRNA NPs), which facilitates BBB penetration. In this study, an siRNA nanocarrier delivery system modified with ApoE peptide (PAPA/siRNA NPs) developed by our research team was employed to simultaneously encapsulate BACE1-siRNA and GSK3β-siRNA. The PAPA/siRNA NPs were prepared through self-assembly and electrostatic binding. The particle size distribution profile and zeta potential of the PAPA/siRNA NPs were analysed with dynamic light scattering, while its morphology was examined with transmission electron microscopy. For in vitro assessments, flow cytometry, confocal laser scanning microscopy, PCR, and Western blotting were employed to evaluate the cellular uptake, gene silencing capacity, and endosomal escape. The biodistribution was investigated by in vivo imaging technology, and the therapeutic effect on AD was verified in AD model mice. The prepared PAPA/siRNA NPs exhibited a regular spherical appearance with a uniform particle size distribution profile. In in vitro cell experiments, the PAPA/siRNA NPs demonstrated excellent cellular uptake ability and efficient endosomal escape. Meanwhile, the dual-loaded siRNA nanocarrier delivery system effectively inhibited the expression of GSK3β and BACE1 genes. In vivo experimental results showed that the siRNA could successfully cross the BBB and deliver to the brain. It not only significantly prolonged the half-life of siRNA but also greatly reduced the generation of pathological β-amyloid and phosphorylated microtubule-associated protein tau, showing excellent therapeutic effects in the treatment of AD. In this study, we successfully constructed a brain-targeted siRNA nanocarrier delivery system for double-gene knockdown. This system can efficiently overcome the obstacle of the BBB, markedly alleviating cognitive and memory deficits in AD mice. It paves the way for novel strategies in the clinical treatment of AD and is expected to bring new breakthroughs and changes to the conquest of this disease. Show less
Dual GIP/GLP-1 receptor agonists have gained significant attention in clinical applications because of their remarkable efficacy in reducing obesity and type 2 diabetes. However, the mechanisms by whi Show more
Dual GIP/GLP-1 receptor agonists have gained significant attention in clinical applications because of their remarkable efficacy in reducing obesity and type 2 diabetes. However, the mechanisms by which these dual agonists affect systemic metabolism remain elusive. To investigate the effects of a novel dual-receptor agonist, THDBH120, on systemic metabolism in obese individuals and the specific roles of GIPR and GLP-1R in modulating systemic and adipose tissue metabolism. To evaluate the intrinsic properties of THDBH120, we conducted a potency assay by using HEK293 cell lines overexpressing either human GIPR or GLP-1R and measured the accumulation of cAMP as a downstream second messenger following receptor activation. To evaluate the efficacy of THDBH120 on systemic metabolism, we used obese rodents and nonhuman primate species that received various doses and frequencies of THDBH120. To determine the metabolic roles of GLP-1R and GIPR in mediating the beneficial effects of THDBH120, we used GLP-1R- and GIPR-knockout mouse models treated with THDBH120, the GLP-1R agonist semaglutide, or the GIPR agonist LAGIPRA and performed transcriptomic sequencing analyses of adipose tissues. THDBH120 is a novel long-acting dual GIPR/GLP-1R agonist that has superior weight loss and metabolic improvement effects in rodents and mammals. The activation of GLP-1R by semaglutide or THDBH120 improved lipid metabolism, whereas the activation of GIPR by LAGIPRA or THDBH120 alleviated inflammation. THDBH120 improved lipid metabolism via GLP-1R-mediated pathways and mitigated inflammation by activating GIPR-associated pathways in the adipose tissues of obese mice. Both GLP-1R and GIPR are important in mediating the beneficial effects of dual receptors on systemic metabolism. THDBH120 is a novel long-acting dual GIPR/GLP-1R agonist that has potential clinical applications. Show less
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease worldwide and is closely associated with obesity, diabetes, and other metabolic disorders. Show more
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease worldwide and is closely associated with obesity, diabetes, and other metabolic disorders. Because MASLD progression poses serious health risks, elucidating the underlying mechanisms is essential to guide early intervention and therapeutic strategies. Proteomic analysis was used to identity high-fat diet (HFD)-induced proteins in mouse liver. Galectin-1 (GAL1) expression was assessed via immunohistochemistry in human liver tissues. Liver-specific GAL1-deficient mice were generated using adeno-associated virus. Mice were fed either a chow diet or an HFD. Functional studies were performed in cell lines using western blotting, RT-qPCR, immunofluorescence, co-immunoprecipitation, mass spectrometry, and molecular docking analysis. GAL1 expression was elevated in liver tissues from patients with MASLD and in mouse models. Liver-specific GAL1 knockdown alleviated hepatic steatosis and enhanced fatty acid oxidation (FAO). Mechanistically, GAL1 competitively bound to the BRCT domain of poly (ADP-ribose) polymerase 1 (PARP1), thereby interfering with its interaction with the WW domain -containing E3 ubiquitin protein ligase 2 (WWP2). Hepatic GAL1 knockdown promoted the PARP1 -WWP2 interaction and subsequently facilitated ubiquitin-dependent degradation of PARP1. This degradation led to increased NAD Hepatic deficiency of GAL1 alleviates hepatic steatosis by enhancing FAO through promotion of ubiquitin-dependent PARP1 degradation, thereby restoring NAD Show less
Hemodynamic abnormalities within atherosclerotic plaque regions, particularly localized high shear stress and endothelial dysfunction, present novel targets for intervention by drug delivery systems. Show more
Hemodynamic abnormalities within atherosclerotic plaque regions, particularly localized high shear stress and endothelial dysfunction, present novel targets for intervention by drug delivery systems. In this study, we designed a polysaccharide-based carrier (HF-AF) from fucoidan, featuring a dynamic supramolecular structure. A dynamic supramolecular network was established within this carrier via dynamic supramolecular interactions between hydroxypropyl-β-cyclodextrin and adamantane-methylamine. The anti-inflammatory compound tilianin, formulated into nanocrystals (Til NCs), was then encapsulated to create a shear-responsive nanosystem (HF-AF@Til NCs). The system's primary therapeutic strategy is its response to pathological hemodynamic forces: upon encountering high shear stress at a stenosis, the supramolecular network undergoes dissociation, triggering a mechanically-gated release of the encapsulated Til NCs. This shear-triggered function is complemented by the natural P-selectin affinity of the fucoidan backbone, which facilitates the anchoring of the nanocarrier at the inflamed lesion site. This sophisticated "anchor-and-release" mechanism enables superior drug accumulation precisely at plaque sites. In ApoE Show less
To investigate the association between vaginal microbiota structure in early pregnancy and gestational diabetes mellitus (GDM) and to characterize microbial signatures for early screening for GDM. The Show more
To investigate the association between vaginal microbiota structure in early pregnancy and gestational diabetes mellitus (GDM) and to characterize microbial signatures for early screening for GDM. The present study was a nested case-control study recruiting pregnant women from the Nanjing Gulou Maternal-Child Health Center, China. Vaginal swabs were collected before 20 weeks of gestation for 16S rRNA sequencing. Following 1:3 propensity score matching, 45 GDM cases and 135 controls were enrolled. The final analysis included 42 GDM cases and 121 controls. A random forest model was used to explore the genera of vaginal differential microbiota associated with GDM. Based on these findings, latent profile analysis (LPA) was conducted to explore potential types of vaginal microbiota, and logistic regression was used to analyze the association between vaginal microbiota types and GDM. The GDM group exhibited elevated alpha diversity (Chao1 index, The composition and structure of vaginal microbiota in early pregnancy are different in the two groups. The vaginal microbiota in early pregnancy, which is characterized by co-dominated by The online version contains supplementary material available at 10.1186/s12866-026-04910-2. Show less
Atherosclerosis preferentially develops in regions exposed to disturbed flow, where is more susceptible to trans-endothelial retention of oxidized low-density lipoprotein (ox-LDL) and subsequent vascu Show more
Atherosclerosis preferentially develops in regions exposed to disturbed flow, where is more susceptible to trans-endothelial retention of oxidized low-density lipoprotein (ox-LDL) and subsequent vascular inflammation. While 12/15-lipoxygenase (12/15-LOX) is implicated in lipid oxidation, its role in accumulation of oxLDL in disturbed flow areas remains unknown. Human coronary artery endarterectomy specimens and cultured endothelial cells were analyzed for 12/15-LOX expression and localization under disturbed flow. Oxidized phospholipids were quantified via E06 antibody by ELISA, while ROS generation was measured using DCFH-DA. ApoE Disturbed flow upregulated 12/15-LOX expression in endothelial cells. In vitro, disturbed flow increased LDL oxidation and ROS production, both attenuated by 12/15-LOX siRNA or the specific inhibitor baicalein and ML351. Genetic deletion or pharmacological inhibition of 12/15-LOX reduced oxidized lipid deposition in disturbed flow regions. Mechanistically, 12/15-LOX increased ROS production in disturbed flow conditions in a pathway upstream of NAPDH oxidase 2. However, the 12/15-LOX-mediated LDL oxidation was independent of NOX. We identify 12/15-LOX as a hemodynamic-sensitive enzyme that is upregulated under disturbed flow to promote LDL oxidation, which proposes a promising target to mitigate atherosclerosis especially in disturbed flow areas. Show less
Chronic obstructive pulmonary disease (COPD) is a systemic condition with comorbidities beyond the lung (eg, cardiovascular and metabolic disorders), and gastrointestinal (GI) disorders are also commo Show more
Chronic obstructive pulmonary disease (COPD) is a systemic condition with comorbidities beyond the lung (eg, cardiovascular and metabolic disorders), and gastrointestinal (GI) disorders are also common. The shared genetic basis of COPD-GI comorbidity and its mediating factors remain unclear. We hypothesized that COPD and GI diseases share pleiotropic genetic architecture implicating lipid-metabolic pathways, with smoking mediating part of the association. We analyzed publicly available European-ancestry GWAS summary statistics for COPD (Global Biobank Meta-analysis Initiative), 15 GI diseases (FinnGen), and smoking phenotypes (UK Biobank). Genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Multi-trait analysis of GWAS (MTAG) boosted COPD discovery by leveraging genetically correlated GI traits. We integrated locus-to-gene mapping with multi-tissue expression quantitative trait loci (eQTL) and plasma protein quantitative trait loci (pQTL) evidence to prioritize shared loci, genes, and proteins. Bidirectional two-sample Mendelian randomization (MR) tested causal directions, and two-step mediation MR evaluated smoking. COPD showed significant genetic correlation with nine GI diseases. We identified six comorbidity-associated loci (three with CADD > 12.37) and 13 unique candidate pleiotropic genes; APOE was supported by proteomic evidence. Enrichment analyses highlighted lipid-metabolism pathways. MR suggested COPD increases risk of gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), acute appendicitis, and gastric ulcer, while diverticular disease showed reverse causality toward COPD. Smoking partially mediated the COPD effect on GERD, acute appendicitis, and gastric ulcer. COPD and multiple GI disorders share a distributed pleiotropic genetic basis within the broader systemic comorbidity spectrum of COPD. Multi-omics evidence supports a genomic pulmonary-intestinal axis in which lipid metabolism and smoking-related mechanisms contribute to COPD and GI comorbidity, providing targets for risk stratification and potential intervention. Show less
The selective cholesteryl ester transfer protein (CETP) inhibitor obicetrapib is in clinical evaluation for dyslipidemia and cardiovascular risk reduction. This study investigated how obicetrapib alon Show more
The selective cholesteryl ester transfer protein (CETP) inhibitor obicetrapib is in clinical evaluation for dyslipidemia and cardiovascular risk reduction. This study investigated how obicetrapib alone and with ezetimibe reduces non-HDL-C, affects atherosclerotic lesion progression, and regression when added to background atorvastatin intervention. APOE∗3-Leiden.CETP mice received a Western-type diet (WTD) or this diet supplemented with obicetrapib, ezetimibe, or both. After 8 weeks, all interventions reduced non-HDL-C levels (obicetrapib: -53%; ezetimibe: -19%; combination: -75%). Obicetrapib mono and combination treatment blocked CETP activity (-99% and -98%), thereby increasing HDL-C levels (+286% and +256%). Very low-density lipoprotein (VLDL) cholesterol production was not affected, while obicetrapib and the combination with ezetimibe increased VLDL clearance (plasma half-life [ Show less
Ren Zhang · 2026 · Trends in molecular medicine · Elsevier · added 2026-04-24
The angiopoietin-like protein (ANGPTL)3/8 complex regulates triglyceride partitioning, and its selective blockade lowers triglycerides while raising HDL-cholesterol (HDL-C). Clinical and genetic evide Show more
The angiopoietin-like protein (ANGPTL)3/8 complex regulates triglyceride partitioning, and its selective blockade lowers triglycerides while raising HDL-cholesterol (HDL-C). Clinical and genetic evidence support ANGPTL3/8 antagonism as a precision therapy for mixed dyslipidemia, monogenic hypertriglyceridemia (CREBH or APOA5 deficiency), and diabetic dyslipidemia by correcting a fundamental disturbance in lipid partitioning. Show less