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关键词： Schizophrenia   Autoimmune   Psychosis   Biomarkers  

摘要： Dear Editor, we were delighted to read the recent article in your journal about a clinical study investigating a possible link between plasma interleukin thirty-three (IL-33) levels and aggression in schizophrenia ( Zhang et al., 2025). It was fou...

关键词： Lithium-on battery   Safety   Ionic liquid   Functional separator   Flame retardant  

摘要： The development of high-performance separator materials has become crucial with the ever-increasing demands for enhanced safety and energy density of lithium-ion batteries in electric vehicles and large-scale energy storage systems. Here, a novel high-safety functionalized separator was prepared by synthesizing a composite material that encapsulates phosphorus-nitrogen-containing ionic liquid (P/N-IL) within NH2-UIO-66-Zr metal-organic framework (MOF), and then combining this composite with a polyvinylidene fluoride (PVDF) P/N-IL@NH2UIO-66/PVDF separator. This functionalized P/N-IL@NH2-UIO-66/PVDF separator significantly improves the flame-retardant performance of NCM811 batteries, effectively mitigating the risks of electrolyte combustion and explosion. Meanwhile, the porous structure of P/N-IL@NH2-UIO-66 material optimizes the Li+ transport pathways, resulting in an increase in the ionic conductivity of NCM811 battery o 3.1 x 10-4 S/cm (compared to only 3.4 x 10-6 S/cm for the pure PVDF separator). The Li+ transference number is also elevated to 0.68. Moreover, after 600 cycles at a 1C current density, the capacity retention rate reaches as high as 71 %, with an average coulombic efficiency of 96 %, substantially enhancing the electrochemical performance and cycling stability of the battery. This work offers a novel technological pathway for the development of high-safety, high-performance lithium-ion batteries, as well as for the application of ionic liquids and MOFs.

关键词： Weighted gene co-expression network analysis   WGCNA   Bisphenol A (BPA)   Preeclampsia (PE)   Single-cell RNA sequencing (scRNA-seq)   Inflammatory Signaling   Molecular Dynamics Simulation (MDS)  

摘要： In hypertensive disorders of pregnancy, particularly preeclampsia, epidemiological associations have increasingly implicated the endocrine disruptor Bisphenol A (BPA), but robust mechanistic evidence remains elusive. Building upon accumulating clinical concern and in vivo data, we pursued an integrative, multi-omic investigation to dissect whether BPA causally and directly contributes to placental maladaptation and vascular dysfunction. Two-sample Mendelian randomization analyses using large European-ancestry genome-wide association datasets demonstrated a significant, directionally concordant relationship between genetically instrumented BPA exposure and preeclampsia risk, supporting causation rather than simple correlation. Single-cell transcriptomic analysis of the maternal-fetal interface identified stromal fibroblasts as a dominant source and target of interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling. Molecular docking and Molecular Dynamics Simulations revealed that BPA binds stably within hydrophobic pockets of IL-6 and, to a lesser extent, STAT3, thereby providing a plausible physical mechanism for ligand-mediated pathway activation. Complementary experiments in human HTR-8/SVneo trophoblasts showed that nanomolar BPA exposure induced dose- and time-dependent STAT3 phosphorylation, promoted IL-6-STAT3 complex formation, and upregulated prototypical downstream genes, including SOCS3, MMP9 and IL-8, hallmarks of inflammation and extracellular matrix remodeling. The concordance between genetic, cellular, structural and functional datasets delineate an integrated cascade in which BPA perturbs fibroblast-centered IL-6/STAT3 signalling, precipitating pro-inflammatory and remodeling responses consistent with preeclampsia pathophysiology. These findings elevate BPA from an associative to a mechanistically credible, modifiable risk factor and nominate stromal IL-6/STAT3 signaling as a therapeutic target for preventing environmen

关键词： Aging   IL-1 beta   Histamine   H1 receptor   Catalepsy   Dopamine metabolism   Dorsal striatum  

摘要： Aging, the strongest risk factor for Parkinson's disease (PD), is associated with brain neuroinflammation. In parkinsonian brain, this inflammation manifests in elevated levels of interleukin-1 beta (IL-1 beta). The pathogenic significance of this factor is unclear. The presented study was aimed to examine the effect of IL-1 beta analogue, rat recombinant IL-1 beta (rrIL-1 beta), on striatal dopamine metabolism in aged rats;in parallel, cataleptogenic action of rrIL-1 beta was determined. Given the ability of IL-1 beta to induce histamine release from histaminergic fibers, the involvement of histamine H1, H2, H3, and H4 receptors in the rrIL-1 beta effects was evaluated. The male Wistar rats of 530-570 days of age were used in all experiments. The experimental groups consisted of 6 animals. The striatal levels of dopamine (DA), 3, 4 -dihydroxyphenylacetic acid (DOPAC), and tyrosine hydroxylase (TH) were determined using HPLC and ELISA;catalepsy was assessed by bar test. Daily i.c.v. administration of rrIL-1 beta for 14 days at 3.0 ng caused significant decrease in DA, DOPAC, and TH levels in the dorsal striatum;these neurochemical changes were accompanied with the development of catalepsy. The observed rrIL-1 beta effects were reversed by H1 antagonist mepyramine whereas H2 and H3/H4 antagonists ranitidine and thioperamide were ineffective. The presented results provide novel insight into functioning of the nigrostriatal pathway in aged rats. Apparently, there exists a certain IL-1 beta-histamine mechanism exerting depletion of dopamine in the dorsal striatum and initiating catalepsy;the mechanism is mediated by H1 receptors. Our data suggest that the IL1 beta-histamine interaction might contribute to the PD development, and be potential target for the treatment of parkinsonism.

关键词： PONV   AP   NLRP3   MCC950   IL-1 beta  

摘要： Background: Postoperative nausea and vomiting (PONV) are common complication following surgical procedures, which can significantly impair the quality of patient care, delay discharge, and hinder the resumption of daily activities. In clinical practice, the incidence of PONV after thyroid surgery is approximately 30 %, with a higher prevalence among female patients. Although existing studies have identified various risk factors, treatment methods, and preventive strategies for PONV, research progress in this field has been relatively slow in recent years. Given that rodents lack a functional emetic reflex, precluding direct observation of vomiting, there remains a paucity of suitable animal models for studying PONV. Prior studies have been confined to anatomical and pharmacological investigations, while research on the molecular, cellular, and neural circuit mechanisms of post-thyroidectomy PONV remains scarce. In the existing research, some scientists have defined the behavior of mice opening their mouths as the occurrence of nausea and vomiting in mice. Here, we aim to establish a rodent model of thyroidectomy-induced retching-like behavior (TIRB) in mice to mimic PONV, thereby enabling systematic characterization of its neural and molecular regulatory pathways. Methods: In this study, a mouse model of retching-like behavior was established using thyroidectomy. Using transcriptomics, we explored the up-regulated genes after TIRB, focusing on finding feasible targets for TIRB treatment. Meanwhile, we used immunofluorescence and qPCR to verify the expression of up-regulated genes. Results: Our screening revealed that IL-1 beta, an inflammatory factor associated with NLRP3, was significantly up-regulated after TIRB. In addition, immunofluorescence revealed a significant increase in NLRP3 expression in area postrema, and treatment with MCC950, a specific NLRP3 inhibitor, decreased retching-like behavior incidence in mice. Conclusion: These results suggest that NLRP3-r

关键词： Interferon   Oncolytic adenoviruses   Combination therapy   Melanoma  

摘要： Melanoma is an aggressive malignancy originating from melanocytes, marked by its high metastatic potential, severe malignancy, and poor prognosis. The primary clinical approach involves surgical resection, complemented by adjuvant therapies such as radiotherapy, chemotherapy, targeted therapies, and immunotherapies. In recent years, high-dose IFN alpha 2b has emerged as a pivotal adjuvant therapy following surgery. However, the clinical remission rate of IFN alpha 2b as a standalone treatment remains limited, prompting deeper exploration into novel immune combination therapies to improve response rate. Oncolytic adenoviruses (OA) selectively target and destroy cancer cells, activate localized immunity, and synergize with other tumor inhibitors, offering a promising new avenue to cancer treatment. In light of this, we investigated the combination of IFN alpha 2b and OA for melanoma treatment. The combination therapy showed excellent tumor inhibition effects in a melanoma mouse model. Importantly, the combination of IFN alpha 2b and OA significantly induced immunogenic tumor cell death and improved tumor antigen presentation compared to either therapy alone. This enhancement bolstered the activation and proliferation of CD8+ T cells, driving a more potent anti-tumor immune response.

关键词： TSLP   Nanobody   Asthma   Komagataella phaffii  

摘要： Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a crucial role in the pathophysiology of asthma, initiating multiple allergic cascade responses. Tezepelumab is the only monoclonal antibody currently approved for marketing, which acts by blocking TSLP binding to TSLPR. However, it is reported that a TSLP trap which simultaneously block TSLP binding with TSLPR and IL-7R alpha has better efficiency in the repression of TSLP signal pathway. In this study, we identified two monovalent nanobodies targeting TSLP through immunization of alpacas and phage display screening. They could block TSLP binding with the TSLPR and IL-7R alpha receptors, respectively. Then, various protein linkers were designed between these two monovalent nanobodies to form different biparatopic nanobodies. We found that the affinity and biological activity of biparatopic nanobodies are related to the length of the linkers and the tandem order of the nanobodies. We screened a biparatopic nanobody CRNB909, which exhibits extremely high binding affinity for human TSLP with a KD < 1E-12 M, demonstrating approximately 40-fold greater potency compared to the Tezepelumab antibody (KD = 3.98E-11 M). Furthermore, it shows superior functional activity in biological assays, displaying 9.2-fold enhanced inhibition of TSLP-mediated JAK-STAT signaling pathway activation and 4.3-fold greater suppression of TSLP-induced BAF3 cell proliferation relative to Tezepelumab. Finally, CRNB909 was successfully secretory expressed in Komagataella phaffii with reduced production costs. This study provides a biparatopic nanobody that could bind TSLP to simultaneously block TSLPR and IL-7R alpha, which might be a promising therapeutant for TSLP related diseases.

关键词： Periapical periodontitis   Lysosomal membrane protein   Dental cementum   Cell death   Autophagy   Signal transduction  

摘要： Apical periodontitis (AP) is globally prevalent and characterized by inflammatory infiltration and periapical bone loss. The systemic RNA interference deficient-1 transmembrane family member 2 (Sidt2) is a nucleic acid transporter that plays essential roles in apoptosis and inflammatory response. However, the effect of Sidt2 on AP remains unknown. In this study, we established an AP mouse model and treated MC3T3-E1 cells and OCCM-30 cells with tumor necrosis factor-alpha (TNF-alpha). Compared to the control groups, the results of Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) analysis confirmed that Sidt2 expression was downregulated in the AP mouse model and TNF-alpha-treated cells, in parallel with increased apoptosis and the production of inflammatory molecules, as evaluated by hematoxylin and eosin staining and immunohistochemistry staining. Furthermore, knockdown of Sidt2 reduced autophagic flux, aggravated TNF-alpha-induced apoptosis and inflammation in vitro, as detected by flow cytometry, Western blot, enzyme-linked immunosorbent assay, and qRT-PCR, and overexpression of Sidt2 yielded the opposite results. In addition, the autophagy inhibitors Chloroquine or 3-Methyladenine could reverse TNF-alpha-induced effects after overexpression of Sidt2. Moreover, knockdown of Sidt2 activated the TNF-alpha-induced p65 signaling, while blocking it with Pyrrolidinedithiocarbamate ammonium suppressed TNF-alpha-induced effects and autophagy. Taken together, our results suggest that Sidt2 ameliorates TNF-alpha-induced apoptosis and inflammation by enhancing autophagic flux via the downregulation of p65 signaling. These results demonstrate that Sidt2 functions as a negative regulator in the apoptosis and inflammatory response of AP, and it may contribute to the development of novel diagnostic and therapeutic approaches for the disease.

关键词： Stress   Depressive   Neutrophils   Lymphocytes   Machine learning   Bone marrow  

摘要： Environmental stress contributes to the development of depression through neuro-immune interactions, yet the underlying molecular mechanisms and associated clinical diagnostic biomarkers remain unclear. We established a psychosocial stress mouse model and systematically investigated the immune dysregulation induced by stress through integrated analysis of blood cell profiles, leukocyte transcriptomics, protein-protein interaction networks, single-cell RNA sequencing, and targeted pharmacological intervention. Additionally, we constructed and validated a depression predictive model using multiparametric peripheral blood data and machine learning, and assessed feature importance using the SHapley Additive exPlanations (SHAP) analysis. The results show that stressed mice exhibited increased neutrophils and decreased lymphocytes, which were positively correlated with depressive-like behaviors. Differential expression analysis identified 127 differentially genes enriched in pathways related to immune response, inflammation regulation, and hematopoietic dysfunction. Hub-genes (Rel, Cd274, Icam1, Tnf, Maff, Nfkbia) were upregulated and drove leukocyte redistribution via inflammatory cascades and adhesion mechanisms, whereas TNF/NF-kappa B pathway inhibition (Etanercept/Infliximab) reversed bone marrow immune imbalance and ameliorated depressive-like behavior. The random forest (RF) model trained with RF-mean features and random oversampling resampling based on blood cell parameters achieved 91.60 % accuracy and an AUC of 0.65. SHAP analysis identified RDW, MOPCT, PLTSI, SII, and NPR as biomarkers. In short, this study elucidates the regulatory role of bone marrow immune remodeling in stress-induced depression and proposes a feasible predictive strategy based on multiparametric peripheral blood profiling.

关键词： Alzheimer's disease   Ferroptosis   IL-17 pathway   TNF pathway   Single-cell sequencing   Network pharmacology  

摘要： Alzheimer's Disease (AD) is a neurodegenerative condition marked by cognitive decline and memory loss, with ferroptosis, an iron-dependent form of regulated cell death, emerging as a contributing factor. This study explored the potential modulatory effects of key components of the traditional Chinese medicine (TCM) formula Linggui Zhugan Decoction (LZD) on microglial ferroptosis in AD, focusing on IL-17 and TNF signaling pathways. Using single-cell RNA sequencing, we observed alterations in microglial populations and ferroptosis-related gene expression in AD mice. Network pharmacology and in vitro experiments indicated that LZD components might influence ferroptosis-related pathways, coinciding with reduced IL-17 and TNF levels in A beta 1-42-treated microglia. In vivo, LZD administration was associated with improved behavioral outcomes and modulation of ferroptosis markers. Although our findings suggest a correlation between LZD treatment and attenuation of ferroptosis-associated pathology, further mechanistic validation is necessary to establish causal links. This study provides preliminary evidence supporting the therapeutic potential of TCM in AD via inflammatory pathway modulation.