Prevalence and Spatial Distribution Characteristics of Female Stress Urinary Incontinence in Mainland China.

Background and objective: Stress urinary incontinence (SUI) in women is a common condition that affects middle-aged and elderly women. Currently, there are still many limitations in the epidemiological research on SUI. This study aims to address the gap in the prevalence of female SUI in mainland China and provide theoretical support for the prevention and treatment of SUI. Methods: A comprehensive literature search was conducted on the prevalence of female SUI in mainland China, systematically searching Chinese and English databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Weipu Database as of April 1, 2024. Detailed criteria for screening and exclusion were established. The prevalence of SUI in the selected studies was synthesized using Stata MP (version 15) software, and a multisubgroup analysis, a sensitivity analysis, and publication bias detection of the prevalence of SUI were also performed using the software. Additionally, ArcGIS software (version 10.8) and Geoda software (version 1.2) were utilized to explore the geographical distribution characteristics of the prevalence of female SUI in mainland China. Key findings and limitations: A total of 688 articles were screened, and finally 85 articles were included. The overall rate of female SUI in mainland China was 24.5% (95% confidence interval: 22.5-26.5%). The heterogeneity of the study is statistically significant (I2 = 99.0%, p < 0.001). Based on significant heterogeneity, a multisubgroup analysis was conducted. The results showed that the prevalence of SUI varies among different publication years, literature quality scores, investigators, study settings, sampling methods, provinces, regions, coastal or inland areas, and rural or urban areas. A spatial econometric analysis indicated that the incidence of SUI in the east-west distribution showed a downward trend, while in the north-south distribution, the incidence rate of SUI showed a trend of first increasing and then decreasing. Additionally, a spatial metrology analysis showed similar trends in the distribution of SUI incidence. Conclusions and clinical implications: The high incidence rate of female SUI in mainland China and the regional differences observed indicate the need for further rigorous epidemiological investigation in the future. Patient summary: Stress urinary incontinence (SUI) is common among middle-aged and elderly women. The high prevalence of SUI in mainland China and the differences across regions emphasize the need for conducting more robust epidemiological studies in the future.

Source-specific ecological and human health risk analysis of topsoil heavy metals in urban greenspace: a case study from Tianshui City, northwest China.

Soil contamination of heavy metals in urban greenspaces can exert detrimental impacts on ecological biodiversity and the health of inhabitants through cross-media migration-induced risks. Here, a total of 72 topsoil samples were collected from greenspaces in the popular tourist city of Tianshui, ranging from areas with parks, residential, road, industrial and educational soils. The study aimed to evaluate an integrated source-specific ecological and human health risk assessment of heavy metals. Among the analyzed heavy metals, except Cr (mean), all exceeded the local background values by 1.30-5.67-fold, and Hg, Cd, Pb and As were the metals with large CV values. The Igeo and CF results showed Hg, Cd, As and Pb exhibited significantly high pollution levels and were the primary pollution factors. The mean PLI values indicated moderate pollution in educational (2.21), industrial (2.07), and road (2.02) soils but slight pollution in park (1.84) and residential (1.39) greenspaces. The Igeo, CF, and PLI results also revealing that these heavy metals are more likely to be affected by human activity. Four primary source factors were identified based on PMF model: coal combustion (25.57%), agricultural sources (14.49%), atmospheric deposition (20.44%) and mixed sources (39.50%). In terms of ecological risk, the mean IRI values showed considerable risks in educational soils (287.52) and moderate risks in road (215.09), park (151.27) and residential (136.71) soils. And the contribution ratio of atmospheric deposition for park, residential, road, industrial and educational greenspaces were 57.72%, 65.41%, 67.69%, 59.60% and 75.76%, respectively. In terms of human health risk, the HI (below 1) and CR (below 1.00E-04) for adults from soils of all land use types was negligible. However, children have more significant non-carcinogenic and carcinogenic hazards especially in residential soils, the HI (above 1) and CR (above 1.00E-04) revealed the significance of regarding legacy As contamination from coal combustion when formulating risk mitigation strategies in this area. The proposed method for source and risk identification makes the multifaceted concerns of pollution and the different relevant risks into a concrete decision-making process, providing robust support for soil contamination control.

Artificial Bacteriophages for Treating Oral Infectious Disease via Localized Bacterial Capture and Enhanced Catalytic Sterilization.

With the rapid emergence of antibiotic-resistant pathogens, nanomaterial-assisted catalytic sterilization has been well developed to combat pathogenic bacteria by elevating the level of reactive oxygen species including hydroxyl radical (·OH). Although promising, the ultra-short lifetime and limited diffusion distance of ·OH severely limit their practical antibacterial usage. Herein, the rational design and preparation of novel virus-like copper silicate hollow spheres (CSHSs) are reported, as well as their applications as robust artificial bacteriophages for localized bacterial capture and enhanced catalytic sterilization in the treatment of oral infectious diseases. During the whole process of capture and killing, CSHSs can efficiently capture bacteria via shortening the distance between bacteria and CSHSs, produce massive ·OH around bacteria, and further iinducing the admirable effect of bacterial inhibition. By using mucosal infection and periodontitis as typical oral infectious diseases, it is easily found that the bacterial populations around lesions in animals after antibacterial treatment fall sharply, as well as the well-developed nanosystem can decrease the inflammatory reaction and promote the hard or soft tissue repair. Together, the high Fenton-like catalytic activity, strong bacterial affinity, excellent antibacterial activity, and overall safety of the nanoplatform promise its great therapeutic potential for further catalytic bacterial disinfection.

Osteocalcin-expressing neutrophils from skull bone marrow exert immunosuppressive and neuroprotective effects after TBI.

Neutrophils from skull bone marrow (Nskull) are activated under some brain stresses, but their effects on traumatic brain injury (TBI) are lacking. Here, we find Nskull infiltrates brain tissue quickly and persistently after TBI, which is distinguished by highly and specifically expressed osteocalcin (OCN) from blood-derived neutrophils (Nblood). Reprogramming of glucose metabolism by reducing glycolysis-related enzyme glyceraldehyde 3-phosphate dehydrogenase expression is involved in the antiapoptotic and proliferative abilities of OCN-expressing Nskull. The transcription factor Fos-like 1 governs the specific gene profile of Nskull including C-C motif chemokine receptor-like 2 (CCRL2), arginase 1 (Arg1), and brain-derived neurotrophic factor (BDNF) in addition to OCN. Selective knockout of CCRL2 in Nskull demonstrates that CCRL2 mediates its recruitment, whereas high Arg1 expression is consistent with its immunosuppressive effects on Nblood, and the secretion of BDNF facilitating dendritic growth contributes to its neuroprotection. Thus, our findings provide insight into the roles of Nskull in TBI.

Cancer-associated fibroblasts mediate resistance to anti-EGFR therapies in cancer.

Over the last decade, epidermal growth factor receptor (EGFR)-targeted therapies have transformed the treatment landscape for patients with advanced solid tumors. Despite these advances, resistance to anti-EGFR therapies is still a significant clinical challenge. While cell-autonomous mechanisms of resistance are well-documented, they do not fully elucidate the complexity of drug resistance. Cancer-associated fibroblasts (CAFs), key mediators within the tumor microenvironment (TME), have emerged as pivotal players in cancer progression and chemoresistance. Recent evidence implicates CAFs in resistance to anti-EGFR therapies, suggesting they may undermine treatment efficacy. This review synthesizes current data, highlighting the critical role of CAFs in resistance pathogenesis and summarizing recent therapeutic strategies targeting CAFs. We underscore the challenges and advocate for the exploration of CAFs as a potential dual-targeted approach.

Highly Crystalline Copper Aluminum-Layered Double Hydroxides with Intrinsic Fenton-Like Catalytic Activity for Robust Oral Health Management.

As the main challenge of dental healthcare, oral infectious diseases are highly associated with the colonization of pathogenic microbes. However, current antibacterial treatments in the field of stomatology still lack a facile, safe, and universal approach. Herein, we report the controllable synthesis of copper aluminum-layered double hydroxides (CuAl-LDHs) with high Fenton-like catalytic activity, which can be utilized in the treatment of oral infectious diseases with negligible side effects. Our strategy can efficiently avoid the unwanted doping of other divalent metal ions in the synthesis of Cu-contained LDHs and result in the formation of binary CuAl-LDHs with high crystallinity and purity. Evidenced by experimental and theoretical results, CuAl-LDHs exhibit excellent catalytic ability toward the ·OH generation in the presence of H2O2 and hold strong affinity toward bacteria, endowing them with great catalytic sterilization against both Gram-positive and Gram-negative bacteria. As expected, these CuAl-LDHs provide outstanding treatments for mucosal infection and periodontitis by promoting wound healing and remodeling of the periodontal microenvironment. Moreover, toxicity investigation demonstrates the overall safety. Accordingly, the current study not only provides a convenient and economic strategy for treating oral infectious diseases but also extends the development of novel LDH-based Fenton or Fenton-like antibacterial reagents for further biomedical applications.

Short Prewarming at 41°C to Correct the Interference in Samples with the Presence of Cold Agglutination.

BACKGROUND: Cold agglutinins (CAs) in blood samples can cause a reversible agglutination of red blood cell (RBC) which result in an incorrect complete blood count (CBC). So, it is important to explore new simple and feasible treatment conditions for clinical work. METHODS: The CAs group included 32 samples with CAs. The parameters of CBC at room temperature or after prewarming at 37°C or 41°C for different time periods were compared. The consistency and correlation of those parameters were analyzed. The morphology of erythrocytes in the CAs group was observed manually. The control group included 45 samples without CAs and prewarmed at 37°C or 41°C for different time periods. The differences were also analyzed. RESULTS: CAs have a significant effect on CBC. After prewarming at 37°C or 41°C the interferences are all corrected. Consider prewarming at 37°C for 120 minutes as the standard procedure. The consistency and correlation analysis showed there was no statistical difference between the results of each subgroup and standard group, except the MCHC of group 41°C 10 minutes. The correlation of parameters between all subgroups and the standard group is satisfied. Microscopic examination showed no RBC aggregation or fragmentation after prewarming at 41°C or 37°C. According to the maximum bias requirements for expert performance in Validation, Verification, and Quality Assurance of Automated Hematology Analyzers, 2nd Edition (CLSI H26-A2), the differences in overall results in control group are negligible. CONCLUSIONS: The 41°C 2 minutes prewarming method is a rapid and effective way for treating samples with CAs. It is an efficient way to obtain more reliable CBC results, without specific instruments.

Efficacy of first-line dual oral pyrotinib plus capetabine therapy in HER2-positive metastatic breast cancer: A real-world retrospective study.

BACKGROUND: The combination of dual-targeted human epidermal growth factor receptor 2 (HER2) therapy and chemotherapy is the standard first-line regimen for recurrent/metastatic breast cancer (mBC). However, the toxicity of such combination therapy can lead to some patients being unable to tolerate adverse events or bear treatment costs. As a novel irreversible pan-ErbB receptor TKI (pyrotinib), can the dual oral administration of pyrotinib plus capetabine (PyroC) provide first-line survival benefits and serve as a more affordable treatment option? METHODS: This real-world retrospective study included patients diagnosed with HER2-positive mBC who received PyroC as a first-line treatment at West China Hospital between May 2018 and July 2023. The survival data and toxicity profiles were reported in this study. RESULTS: A total of 64 patients received PyroC as first-line therapy. The median progression-free survival (PFS) was 19.6 months (95% CI 15.0-27.2), while overall survival (OS) has not yet been reached. Kaplan-Meier analysis indicated that age (≥60, p = 0.03) and metastasis sites (p = 0.004) were related to poor efficacy of PyroC, while there was no relationship between effectiveness and menstrual status, hormone receptor (HR) status or previous treatment with anti-HER2 therapy. Furthermore, the objective response rate (ORR) and disease control rate (DCR) were 79.7% and 98.4%, respectively. Of the patients, 78.1% reported treatment-related adverse events (TRAEs). The predominant adverse events were diarrhea (n = 46, 71.9%) and hand-foot syndrome (n = 10, 15.6%). CONCLUSION: The dual oral administration regimen (PyroC) has a promising ORR or PFS in HER2-positive mBC patients, with an acceptable safety profile and convenience.

MiR-574-5p activates human TLR8 to promote autoimmune signaling and lupus.

Endosomal single-stranded RNA-sensing Toll-like receptor-7/8 (TLR7/8) plays a pivotal role in inflammation and immune responses and autoimmune diseases. However, the mechanisms underlying the initiation of the TLR7/8-mediated autoimmune signaling remain to be fully elucidated. Here, we demonstrate that miR-574-5p is aberrantly upregulated in tissues of lupus prone mice and in the plasma of lupus patients, with its expression levels correlating with the disease activity. miR-574-5p binds to and activates human hTLR8 or its murine ortholog mTlr7 to elicit a series of MyD88-dependent immune and inflammatory responses. These responses include the overproduction of cytokines and interferons, the activation of STAT1 signaling and B lymphocytes, and the production of autoantigens. In a transgenic mouse model, the induction of miR-574-5p overexpression is associated with increased secretion of antinuclear and anti-dsDNA antibodies, increased IgG and C3 deposit in the kidney, elevated expression of inflammatory genes in the spleen. In lupus-prone mice, lentivirus-mediated silencing of miR-574-5p significantly ameliorates major symptoms associated with lupus and lupus nephritis. Collectively, these results suggest that the miR-574-5p-hTLR8/mTlr7 signaling is an important axis of immune and inflammatory responses, contributing significantly to the development of lupus and lupus nephritis.

A long non-coding RNA functions as a competitive endogenous RNA to modulate TaNAC018 by acting as a decoy for tae-miR6206.

Increasing evidence indicates a strong correlation between the deposition of cuticular waxes and drought tolerance. However, the precise regulatory mechanism remains elusive. Here, we conducted a comprehensive transcriptome analysis of two wheat (Triticum aestivum) near-isogenic lines, the glaucous line G-JM38 rich in cuticular waxes and the non-glaucous line NG-JM31. We identified 85,143 protein-coding mRNAs, 4,485 lncRNAs, and 1,130 miRNAs. Using the lncRNA-miRNA-mRNA network and endogenous target mimic (eTM) prediction, we discovered that lncRNA35557 acted as an eTM for the miRNA tae-miR6206, effectively preventing tae-miR6206 from cleaving the NAC transcription factor gene TaNAC018. This lncRNA-miRNA interaction led to higher transcript abundance for TaNAC018 and enhanced drought-stress tolerance. Additionally, treatment with mannitol and abscisic acid (ABA) each influenced the levels of tae-miR6206, lncRNA35557, and TaNAC018 transcript. The ectopic expression of TaNAC018 in Arabidopsis also improved tolerance toward mannitol and ABA treatment, whereas knocking down TaNAC018 transcript levels via virus-induced gene silencing in wheat rendered seedlings more sensitive to mannitol stress. Our results indicate that lncRNA35557 functions as a competing endogenous RNA to modulate TaNAC018 expression by acting as a decoy target for tae-miR6206 in glaucous wheat, suggesting that non-coding RNA has important roles in the regulatory mechanisms responsible for wheat stress tolerance.

FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Scoping review of obesity interventions: Research frontiers and publication status.

Obesity and overweight are significant global health issues, and numerous obesity intervention studies have been conducted. Summarizing current knowledge of interventions aims to inform researchers and policymakers to keep up-to-date with the latest scientific advancements and trends. In this review, we comprehensively retrieved and screened 4,541 studies on obesity intervention published between 2018 and 2022 in the Web of Science Core Collection, and objectively presented research frontiers using bibliometric analysis. The research frontiers of intervention are mainly focused on dietary, exercise, pharmacological interventions, bariatric surgery, environmental, and cognitive interventions. Time-restricted eating is the hottest research topic, followed by probiotics and Roux-en-Y gastric bypass. Gut microbiota is located in the "Basic and transversal themes" quadrant with a high centrality and low density, which has great development potentiality. Obesity intervention is becoming increasingly common,and we advocate for researchers to undertake more focused research endeavors that consider the specific characteristics of diverse populations or patients.

The crucial role of age and site in incidence and prognosis of female neuroendocrine neoplasms in the United States: a population-based study from 2000 to 2018.

BACKGROUND: As the incidence continues to rise, global concern about neuroendocrine neoplasms (NENs) is mounting. However, little is known about how NENs affect women patients. METHODS: The annual percentage change (APC) was calculated to describe the incidence. Cox proportional hazards multivariable regression was used to identify risk factors. The nomograms were employed to estimate prognosis. RESULTS: A total of 39,237 female NENs (fNENs) cases were identified. The incidence of fNENs increased annually (APC = 4.5, 95% CI 4.1-4.8, P < 0.05), and the incidence pattern and survival outcomes showed age and site-specificity. Appendiceal, rectal, and pulmonary fNENs were major contributors to the incidence of patients younger than 40, between 40-59, and over 60 years old, respectively. The Cox proportional hazards regression model revealed that age, tumor size, grade, stage, and primary sites were closely related to survival. The worst survival outcomes appeared in breast, reproductive system, and liver fNENs for patients under 40, between 40-49, and over 50 years old, respectively. A nomogram based on these developed with higher predictive accuracy of prognosis, with a C index of 0.906 in the training cohort and 0.901 in the validation cohort. CONCLUSIONS: Our findings revealed distinct site-specific tendencies in the incidence and survival patterns among fNEN patients across various age groups. Thus, reasonable patient screening and stratification strategies should be implemented, especially for young patients.

A cretaceous frog with eggs from northwestern China provides fossil evidence for sexual maturity preceding skeletal maturity in anurans.

Mesozoic fossils of frogs are rare in the palaeontological record, particularly those exhibiting soft tissues that offer limited insights into early life-history characteristics. Here we report on a skeletally immature frog from the Lower Cretaceous of northwest China, with egg masses in the body and eggs in the oviduct, indicative of a gravid female. CT reconstruction of the specimen allows referral to Gansubatrachus qilianensis and we assign it as a paratype complementing the diagnosis of the type species. The new fossil, which might represent a younger individual than the holotype of Gansubatrachus, shows that sexual maturation occurred before full adulthood in this frog and provides evidence of death linked to mating behaviour. We also discuss other potential sources of variation and life-history traits of Gansubatrachus. The new finding represents the oldest Early Cretaceous frog preserving in situ eggs and provides a glimpse into ancient anuran development during Mesozoic times.

A bibliometric and knowledge-map analysis of bispecific antibodies in cancer immunotherapy from 2000 to 2023.

Background: Bispecific antibody (BsAb)-based cancer immunotherapy has provided new avenues for the treatment of various malignancies. The approval of Blinatumomab has encouraged further investigation into these treatments, and a series of preclinical and clinical trials have been conducted, together with the publication of numerous articles. Here, the knowledge structure of BsAb-based cancer immunotherapy is summarized using bibliometric analysis to provide in-depth insight into current research trends and foci. Methods: The studies included in the bibliometric analysis of BsAbs in cancer immunotherapy were retrieved from the online Web of Science Core Collection (WOSCC) database on April 16th, 2023. Visualization analysis was performed with the help of CtieSpace (version 6.2.2.msi [64-bit]), VOSviewer (version 1.6.19), R (version 4.2.1), and the Bibliometric analysis platform (R-based online data processing tool). Results: A total of 1750 papers were identified. Analysis of annual publications and total citations indicated that publications have increased steadily over the past few decades. The USA, followed by Germany, had largest number of publications, making significant contributions to the field. The Memorial Sloan Kettering Cancer Center received the highest number of citations (n = 3769). However, its collaboration and cooperation with different institutions require further strengthening. MAbs and Clinical Cancer Research published the most papers, while Blood and Cancer Research were the most commonly co-cited journals. DM Goldenberg from the USA published the most articles with the highest H-index (34), and the most co-cited author (2137 citations) was PA Baeuerle; both these authors have distinguished achievements in this field. Analysis of co-cited references and keywords showed that the hotspots and research focus on the use of BsAbs for solid tumors have increased rapidly while the application of BsAb immunotherapy in hematologic malignancies has expanded significantly. The hot topics in the field included cytokine release syndrome, the efficacy and safety of BsAbs, resistance mechanisms, and the exploration and optimization of combination therapies. Conclusion: Cancer immunotherapies based on BsAbs are a hot topic in research. Current studies focus on the construction and optimization of BsAb structure, as well as their combination with other treatment modalities to improve their efficacy and overcome resistance. Furthermore, it is expected that the ongoing investigation of BsAb-based immunotherapy for solid tumors will bear fruit with significant clinical application prospects in the near future.

Revision surgery for periprosthetic fracture of distal femur after endoprosthetic replacement of knee joint following resection of osteosarcoma.

Purpose: Periprosthetic fracture (PPF) is one of the severe complications in patients with osteosarcoma and carries the risk of limb loss. This study describes the characteristics, treatment strategies, and outcomes of this complication. Methods: Patients were consecutively included who were treated at our institution between 2016 and 2020 with a PPF of distal femur. The treatment strategies included two types: 1) open reduction and internal fixation with plates and screws and 2) replacement with long-stem endoprosthesis and reinforcement with wire rope if necessary. Results: A total of 11 patients (mean age 12.2 years (9-14)) were included, and the mean follow-up period was 36.5 (21-54) months. Most fractures were caused by direct or indirect trauma (n = 8), and others (n = 3) underwent PPF without obvious cause. The first type of treatment was performed on four patients, and the second type was performed on seven patients. The mean Musculoskeletal Tumor Society (MSTS) score was 20 (17-23). All patients recovered from the complication, and limb preservation could be achieved. Conclusion: PPF is a big challenge for musculoskeletal oncologists, particularly in younger patients. Additionally, PPF poses a challenge for orthopedic surgeons, as limb preservation should be an important goal. Hence, internal fixation with plates and endoprosthetic replacement are optional treatment strategies based on fracture type and patient needs.

Metabotropic glutamate receptor 5 promotes blood-brain barrier recovery after traumatic brain injury.

Blood-brain barrier (BBB) impairment and glutamate release are two pathophysiological features of traumatic brain injury (TBI), contributing to secondary brain damage and neuroinflammation. However, our knowledge of BBB integrity damage and dysfunction are still limited due to the diverse and fluctuating expression of glutamate receptors after trauma. Here, we confirmed the downregulation of metabotropic glutamate receptor 5 (mGluR5) on microvascular endothelial cell within the acute phase of TBI, and the recovered mGluR5 levels on BBB was positively associated with blood perfusion and neurological recovery. In whole body mGluR5-knockout mice, BBB dysfunction and neurological deficiency were exacerbated after TBI compared with wild type mice. In terms of mechanism, the amino acid sequence 201-259 of cytoskeletal protein Alpha-actinin-1 (ACTN1) interacted with mGluR5, facilitating mGluR5 translocation from cytoplasmic compartment to plasma membrane in endothelial cells. Activation of plasma membrane mGluR5 triggers the PLC/PKCµ/c-Jun signaling pathway, leading to increased expression of the tight junction-actin cytoskeleton connecting protein zonula occludens-1 (ZO-1). Our findings uncover a novel mechanism mediated by membrane and cytoplasmic mGluR5 in endothelial cell integrity maintenance and repair, providing the potential therapeutic target for TBI treatment targeting at mGluR5 and mGluR5/ACTN1 complex in BBB.