Energy stress induced cardiac autophagy detection via a chronic and dynamic cardiomyocytes-based biosensing platform.

Hypoglycemia is a common complication which occurs during the treatment of diabetes, closely associated with cardiovascular events. A sudden decrease in blood glucose increases the risk of arrhythmia, which can lead to sudden cardiac death. This event is usually accompanied by abnormal electrophysiological activities in cardiomyocytes. However, traditional models do not efficiently reflect real-time cardiomyocyte electrophysiological changes under various glucose deprivation conditions in a large-scale and high-throughput manner. Therefore, we need to develop a new biosensing platform to aid in related scientific research. In this study, a cardiomyocyte-based biosensor was developed for real-time, noninvasive monitoring of the electrophysiological responses of cardiomyocytes under different glucose concentrations. The findings show that low-glucose conditions result in abnormal electrophysiology in cardiomyocytes, but autophagy enables cells to survive this adversity. Inhibition of autophagy exacerbates electrophysiological abnormalities, and long-term glucose starvation causes irreversible damage to cardiomyocytes. The proposed chronic and dynamic cardiomyocyte-based biosensing platform provides a new tool for understanding the effects of hypoglycemia on the in vitro cardiomyocyte-based heart model, revealing that autophagy has the potential to be an alternative treatment for diabetes and hypoglycemia.

A light-addressable potentiometric sensor-based extracellular calcium dynamic monitoring and imaging platform for cellular calcium channel drug evaluation.

Disruption and dysregulation of cellular calcium channel function can lead to diseases such as ischemic stroke, heart failure, and arrhythmias. Corresponding calcium channel drugs typically require preliminary efficacy evaluations using in vitro models such as cells and simulated tissues before clinical testing. However, traditional detection and evaluation methods often encounter challenges in long-term continuous monitoring and lack calcium specificity. In this study, a dynamic monitoring system based on ion-sensitive membranes for light-addressable potentiometric sensor (LAPS) was developed to meet the demand for monitoring changes in extracellular calcium ion (Ca2+) concentration in live cells. The effects of Ca2+ channel agonists and blockers on 2D and 3D HL-1 cells were investigated, with changes in extracellular Ca2+ concentration reflecting cellular calcium metabolism, facilitating drug evaluation. Additionally, calcium imaging technology with optical addressing capability complemented the LAPS system's ability to perceive 3D cell morphology, enhancing its drug evaluation capabilities. This work provides a novel, label-free, specific, and stable technique for monitoring cellular calcium metabolism. It achieves both continuous monitoring at single points and custom sensing area calcium imaging, holding significant implications for drug screening and disease treatment related to human calcium homeostasis.

Safety of Kidney Transplantation from Donors with HIV.

BACKGROUND: Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS: In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS: We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS: In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).

Bilateral hearing loss caused by anti-NMDA receptor encephalitis with teratoma: A case report.

Autoimmune encephalitis (AE) is an autoimmune disease in the central nervous system. Clinical manifestations include cognitive dysfunction, psychiatric-behavioral abnormalities, epilepsy, motor disorders, speech disorders, and memory impairment. Some patients do not have the characteristic clinical manifestations of the disease when they see a doctor, so they are easily diagnosed incorrectly. Autoimmune antibodies originate from genetic and acquired factors. Clinical data have found a correlation between ovarian teratoma and autoimmune encephalitis. This case reports a 34-year-old woman who was diagnosed with teratoma-associated anti-N-methyl-D- aspartate receptor-mediated autoimmune encephalitis called anti-N-methyl-D-aspartate receptor encephalitis with bilateral hearing loss in 2021. Through this case report, clinicians will pay attention to autoimmune encephalitis and raise awareness of the specific clinical manifestations of autoimmune encephalitis, and focus on early identification. It means that clinicians should be familiar with the representative clinical manifestations of the disease.

Are toe fringes important for lizard burying in highly mobile sand?

Toe fringes are a key innovation for sand dwelling lizards, and the relationship between toe fringe function and substrate properties is helpful in understanding the adaptation of lizards to sand dune environments. We tested the sand burial performance of Phrynocephalus mystaceus on different sand substrates with toe fringe manipulation, with the aim of assessing whether the function of the toe fringes shifts under different substrate properties, especially in highly mobile substrates. The sand burial performance of P. mystaceus was influenced by substrate properties in relation to the toe fringe states of the lizard. After removal of the bilateral toe fringes, the sand burial ability score of P. mystaceus was significantly higher on sand substrates below 100 mesh than on native sand substrates. As the angle of stability of the substrate properties decreased, the sand burial performance of the lizard was even better after the bilateral toe fringes were removed. The results of the LASSO model and the path analysis model showed that the stability angle provided the opposite effect on sand burial performance in different toe fringe states. These results further suggest that the sand burial function of toe fringes may not be suitable for highly mobile sand substrates. It remains to be tested further whether the function of toe fringes is more important for running on sand.

Relationship between parents' anxiety, stress, depression and their children's health-related quality of life and psychological well-being during the COVID-19 outbreak in Iran.

BACKGROUND: In late 2019, a new respiratory illness was detected in Wuhan, China and was later designated as COVID-19 by the WHO. Despite international efforts to impose restrictions and quarantine measures, the virus spreads rapidly across the globe. The pandemic has significantly impacted the mental health of both children and parents. This study investigates the relationship between parents' anxiety, stress and depression, and Children's Health-Related Quality of Life (CHQol) and externalised behavioural disorders during the COVID-19 pandemic. METHODS: This is a cross-sectional study that included 396 parents who have children between the ages of 6 and 18 years old. Sampling was done by designing an online questionnaire that was distributed on social media (WhatsApp and Telegram and native social media, such as Eitaa, Soroush and E-Gap). Inclusion criteria were all citizens living in rural and urban areas of Rafsanjan, citizens living in Rafsanjan city for 1 year and having children aged 6-18 years old. We used a demographic information questionnaire, Depression, Anxiety, Stress Scale-21, CHQol and Achenbach System of Empirically Based Assessment to collect data. RESULTS: We found a positive significant correlation between anxiety (r=0.334), stress (r=0.354), depression (r=0.324) and externalised behavioural disorder (p<0.001). Depression and anxiety predicted 22% of the variance of the CHQol (p<0.001) while age, stress, use of masks and gloves to prevent infection, and anxiety predicted 19% of the variance of externalised behavioural disorder (p<0.001). CONCLUSION: Parents experienced high levels of symptoms of anxiety, stress and depression during the COVID-19 outbreak, which can be associated with behavioural disorders in their children and negatively impact their health. Therefore, it is crucial to pay more attention to the mental state of parents and its complications for children.

Visualization of Diabetes Progression by an Activatable NIR-IIb Luminescent Probe.

Developing NIR-IIb luminescence probes with rapid visualization and a high penetration depth is essential for diabetes research. Combining a sensitizing switch with lanthanide-doped nanoparticles (LnNPs) has been employed to fabricate the NIR-IIb probes. However, these probes mainly adopt heptamethine cyanine dye as the antenna, and the NIR-IIb signal is activated by inhibiting the photoinduced electron transfer (PET) of the dye. Due to limited recognition units, this strategy makes many biomolecules undetectable, such as cysteine (Cys), which is closely related to diabetes. Herein, in this article, hemicyanine dye, NFL-OH, was verified as a new antenna to sensitize NIR-IIb emission from LnNPs. Unlike traditional cyanine dyes, hemicyanine's fluorescence intensity can also be modulated by intramolecular charge transfer (ICT), thereby expanding the range of detectable targets for NIR-IIb probes based on sensitization mechanism. Through switching the hemicyanine-sensitized NIR-IIb emission, we successfully fabricated an NFL-Cys-LnNPs' nanoprobe, which can effectively monitor Cys concentration in the liver of diabetic mice during diabetes progression and evaluate the efficacy of diabetic drugs. Our work not only presents an excellent tool for Cys imaging but also introduces new concepts for designing NIR-IIb probes.

Carrier-free cryptotanshinone-peptide conjugates self-assembled nanoparticles: An efficient and low-risk strategy for acne vulgaris.

Acne vulgaris ranks as the second most prevalent dermatological condition worldwide, and there are still insufficient safe and reliable drugs to treat it. Cryptotanshinone (CTS), a bioactive compound derived from traditional Chinese medicine Salvia miltiorrhiza, has shown promise for treating acne vulgaris due to its broad-spectrum antimicrobial and significant anti-inflammatory properties. Nevertheless, its local application is hindered by its low solubility and poor skin permeability. To overcome these challenges, a carrier-free pure drug self-assembled nanosystem is employed, which can specifically modify drug molecules based on the disease type and microenvironment, offering a potential for more effective treatment. We designed and synthesized three distinct structures of cationic CTS-peptide conjugates, creating self-assembled nanoparticles. This study has explored their self-assembly behavior, skin permeation, cellular uptake, and both in vitro and in vivo anti-acne effects. Molecular dynamics simulations revealed these nanoparticles form through intermolecular hydrogen bonding and π-π stacking interactions. Notably, self-assembled nanoparticles demonstrated enhanced bioavailability with higher skin permeation and cellular uptake rates. Furthermore, the nanoparticles exhibited superior anti-acne effects compared to the parent drug, attributed to heightened antimicrobial activity and significant downregulation of the MAPK/NF-κB pathway, leading to reduced expression of pro-inflammatory factors including TNF-α, IL-1ß and IL-8. In summary, the carrier-free self-assembled nanoparticles based on CTS-peptide conjugate effectively address the issue of poor skin bioavailability, offering a promising new approach for acne treatment.

DMDD, isolated from Averrhoa carambola L., ameliorates diabetic nephropathy by regulating endoplasmic reticulum stress-autophagy crosstalk.

BACKGROUND: Studies have shown that Averrhoa carambola L. possesses therapeutic potential for diabetes and related complications. However, the specific beneficial effects and molecular mechanisms of 2-dodecyl-6-meth-oxycyclohexa-2,5-diene-1,4-dione (DMDD) isolated from Averrhoa carambola L. on diabetic nephropathy (DN) require further investigation. METHODS: 80 C57BL/6 J male mice were subjected to a 1-week adaptive feeding, followed by a high-fat diet and intraperitoneal injection of 100 mg/kg streptozotocin (STZ) to construct an in vivo DN model. Additionally, human renal proximal tubular epithelial cells (HK-2) induced by high glucose (HG) were used as an in vitro DN model. The expression levels of epithelial-mesenchymal transition (EMT), endoplasmic reticulum stress (ERS), and autophagy-related proteins in renal tubular cells were detected by Western Blot, flow cytometry, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) staining. Transcriptome analysis revealed was conducted to elucidate the specific mechanism of by which DMDD mitigates DN by inhibiting ERS and autophagy. HK-2 cells were transfected with IRE1α overexpression lentivirus to reveal the role of IRE1α overexpression in HG-induced HK-2. RESULTS: The experimental data showed that DMDD significantly reduced blood glucose levels and improved renal pathological alterations in DN mice. Additionally, DMDD inhibited the calcium (Ca2+) pathway, manifested by decreased autophagosome formation and downregulation of LC3II/I, Beclin-1, and ATG5 expression. Moreover, in HG-induced HK-2 cells, DMDD suppressed the overexpression of GRP78, CHOP, LC3II/I, Beclin1, and ATG5. Notably, IRE1α overexpression significantly increased autophagy incidence; however, DMDD treatment subsequently reduced the expression of LC3II/I, Beclin1, and ATG5. CONCLUSION: DMDD effectively inhibits excessive ERS and autophagy, thereby reducing renal cell apoptosis through the IRE1α pathway and Ca 2+ pathway.

MTF2 facilitates the advancement of osteosarcoma through mediating EZH2/SFRP1/Wnt signaling.

BACKGROUND: Osteosarcoma is a soft tissue neoplasm with elevated recurrence risk and highly metastatic potential. Metal response element binding transcriptional factor 2 (MTF2) has been revealed to exert multiple activities in human tissues. The present research was conducted to explore the functions and related response mechanism of MTF2 in osteosarcoma which have not been introduced yet. METHODS: Bioinformatics tools identified the differential MTF2 expression in osteosarcoma tissues. MTF2 expression in osteosarcoma cells was examined with Western blot. Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EDU) staining, wound healing as well as transwell assays measured cell proliferation, migration and invasion, respectively. Flow cytometry assay detected the cellular apoptotic level. Western blot also measured the expressions of proteins associated with epithelial mesenchymal transition (EMT), apoptosis and enhancer of zeste homolog 2 (EZH2)/secreted frizzled-related protein 1 (SFRP1)/Wnt signaling. Co-immunoprecipitation (Co-IP) assay confirmed MTF2-EZH2 interaction. RESULTS: MTF2 expression was increased in osteosarcoma tissues and cells. MTF2 interference effectively inhibited the proliferation, migration and invasion of osteosarcoma cells and promoted the cellular apoptotic rate. MTF2 directly bound to EZH2 and MTF2 silence reduced EZH2 expression, activated SFRP1 expression and blocked Wnt signaling in osteosarcoma cells. EZH2 upregulation or SFRP1 antagonist WAY-316606 partly counteracted the impacts of MTF2 down-regulation on the SFRP1/Wnt signaling and the biological phenotypes of osteosarcoma cells. CONCLUSIONS: MTF2 might down-regulate SFRP1 to activate Wnt signaling and drive the progression of osteosarcoma via interaction with EZH2 protein.

Effects of perioperative hydrogen inhalation on brain edema and prognosis in patients with glioma: a single-center, randomized controlled study.

Introduction: Brain edema is a life-threatening complication that occurs after glioma surgery. There are no noninvasive and specific treatment methods for brain edema. Hydrogen is an anti-inflammatory and antioxidant gas that has demonstrated therapeutic and preventative effects on several diseases, particularly in the nervous system. This study aimed to determine the therapeutic effects of hydrogen administration on brain edema following glioma surgery and elucidate its mechanism. Methods: A single-center, randomized controlled clinical trial of hydrogen inhalation was conducted (China Clinical Trial Registry [ChiCTR-2300074362]). Participants in hydrogen (H) group that inhaled hydrogen experienced quicker alleviation of postoperative brain edema compared with participants in control (C) group that inhaled oxygen. Results: The volume of brain edema before discharge was significantly lower in the H group (p < 0.05). Additionally, the regression rate of brain edema was higher in the H group than in the C group, which was statistically significant (p < 0.05). Furthermore, 3 days after surgery, the H group had longer total sleep duration, improved sleep efficiency, shorter sleep latency, and lower numerical rating scale (NRS) scores (p < 0.05). Discussion: In conclusion, hydrogen/oxygen inhalation effectively reduced postoperative brain edema in glioma patients. Further research is necessary to understand the underlying mechanisms of hydrogen's therapeutic effects. Hydrogen is expected to become a new target for future adjuvant therapy for brain edema.

Prediction of 90 day readmission in heart failure with preserved ejection fraction by interpretable machine learning.

AIMS: Certain critical risk factors of heart failure with preserved ejection fraction (HFpEF) patients were significantly different from those of heart failure with reduced ejection fraction (HFrEF) patients, resulting in the limitations of existing predictive models in real-world situations. This study aimed to develop a machine learning model for predicting 90 day readmission for HFpEF patients. METHODS AND RESULTS: Data were extracted from electronic health records from 1 August 2020 to 1 August 2021 and follow-up records of patients with HFpEF within 3 months after discharge. Feature extraction was performed by univariate analysis combined with the least absolute shrinkage and selection operator (LASSO) algorithms. Machine learning models like eXtreme Gradient Boosting (XGBoost), random forest, neural network and logistic regression were adopted to construct models. The discrimination and calibration of each model were compared, and the Shapley Additive exPlanations (SHAP) method was used to explore the interpretability of the model. The cohort included 746 patients, of whom 103 (13.8%) were readmitted within 90 days. XGBoost owned the best performance [area under the curve (AUC) = 0.896, precision-recall area under the curve (PR-AUC) = 0.868, sensitivity = 0.817, specificity = 0.837, balanced accuracy = 0.827]. The Kolmogorov-Smirnov (KS) statistic was 0.694 at 0.468 in the XGBoost model. SHAP identified the top 12 risk features, including activities of daily living (ADL), left atrial dimension (LAD), left ventricular end-diastolic diameter (LVDD), shortness, nitrates, length of stay, nutritional risk, fall risk, accompanied by other symptoms, educational level, anticoagulants and edema. CONCLUSIONS: Our model could help medical agencies achieve the early identification of 90 day readmission risk in HFpEF patients and reveal risk factors that provide valuable insights for treatments.

Using preimplantation genetic testing for monogenic disease for preventing citrullinemia type 1 transmission.

Aim: The aim of this study is to investigate if Preimplantation Genetic Testing (PGT) can effectively identify unreported variants according to American College of Medical Genetics and Genomics (ACMG)to prevent citrullinemia type 1 affection. Design: This study involves a detailed case analysis of a family with history of citrullinemia type 1, focusing on the use of PGT for monogenic diseases (PGT-M). The genetic variants were identified using ACMG guidelines, and PGT was employed to prevent the inheritance of these variants. The study included haplotype analysis and Sanger sequencing to confirm the results. Results: The study identified previously unreported variations in the ASS1 gene causing citrullinemia type 1. PGT successfully prevented the transmission of these variants, resulting in the birth of a healthy fetus. However, challenges such as allele dropout (ADO) and gene recombination were encountered during haplotype analysis, which could potentially defeat the diagnosis. The study demonstrated that combining haplotype analysis with Sanger sequencing can enhance the accuracy of PGT. Conclusion: Preimplantation Genetic Testing (PGT) targeting likely pathogenic and pathogenic variants in the ASS1 gene, as rated by ACMG, allows the birth of healthy infants free from citrullinemia type 1. Additionally, the establishment of single haplotypes and Sanger sequencing can reduce the misdiagnosis rate caused by allele dropout (ADO) and genetic recombination.

Selenium spatial distribution and bioavailability of soil-plant systems in China: a comprehensive review.

Selenium (Se) has a dual nature, with beneficial and harmful effects on plants, essential for both humans and animals, playing a crucial role in ecosystem regulation. Insufficient Se in specific terrestrial environments raises concerns due to its potential to cause diseases, while excess Se can lead to severe toxicity. Thus, maintaining an optimal Se level is essential for living organisms. This review focuses first on Se transformation, speciation, and geochemical properties in soil, and then provides a concise overview of Se distribution in Chinese soil and crops, with a focus on the relationship between soil Se levels and parent materials. Additionally, this paper explores Se bioavailability, considering parent materials and soil physicochemical properties, using partial least squares path modeling for analysis. This paper aimed to be a valuable resource for effectively managing Se-enriched soil resources, contributing to a better understanding of Se role in ecosystems.

Dietary patterns suggest that dark chocolate intake may have an inhibitory effect on oral cancer: a Mendelian randomization study.

Background: Previous studies reported that variations in dietary intake patterns substantially impact human health, specifically tumorigenesis. However, confounding factors in previous cohort studies have obscured the relationship between dietary differences and the risk of oral cancer (OC). Materials and methods: We developed an outcome dataset from genome-wide association studies (GWAS) data on three OCs within the GAME-ON project, using GWAS-META merging. We extracted 21 dietary exposures, including 10 dietary patterns, 6 vitamins, and 5 micronutrients, from the UK Biobank database, using the inverse variance weighting method as the primary statistical method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy. Serum metabolite concentrations were adjusted using multivariate Mendelian randomization. Results: Of the 10 analyzed dietary patterns, 8 showed no significant association with the risk of developing OC. Consumption of dark chocolate (inverse variance weighted [IVW]: Odds ratio (OR) = 0.786, 95% confidence interval [CI]: 0.622-0.993, p = 0.044) and sweet pepper exhibited an inverse relationship with OC risk (IVW: OR = 0.757, 95% CI: 0.574-0.997, p = 0.048). Reverse MR analysis revealed no reverse causality. Furthermore, no significant correlation was observed between the intake of 6 vitamins and 5 micronutrients and the risk of developing OC. After using multivariable MR to adjust for serum caffeine, linoleate, theophylline, and theobromine metabolism levels, consuming dark chocolate was unrelated to a decreased risk of OC. After adjusting each serum metabolite individually, the observed p-values deviated from the original values to varying degrees, indicating that the components of dark chocolate could have different effects. Among these components, theophylline demonstrated the most significant inhibitory effect. Conclusion: This study demonstrated a causal relationship between the intake of dark chocolate and sweet peppers and a lower risk of OC. The components of dark chocolate could have different effects.

Association study of Plasmodium falciparum Acetyl-CoA Synthetase Mutations S868G and V949I with antimalarial drugs.

Plasmodium falciparum acetyl-CoA synthetase (PfACAS) protein is an important source of acetyl-CoA. We detected the mutations S868G and V949I in PfACAS by whole-genome sequencing analysis in some recrudescent parasites after antimalarial treatment with artesunate and dihydroartemisinin-piperaquine, suggesting that they may confer drug resistance. Using CRISPR/Cas9 technology, we engineered parasite lines carrying the PfACAS S868G and V949I mutations in two genetic backgrounds and evaluated their susceptibility to antimalarial drugs in vitro. The results demonstrated that PfACAS S868G and V949I mutations alone or in combination were not enough to provide resistance to antimalarial drugs.

Advancing Ionic Liquid Research with pSCNN: A Novel Approach for Accurate Normal Melting Temperature Predictions.

Ionic liquids (ILs), known for their distinct and tunable properties, offer a broad spectrum of potential applications across various fields, including chemistry, materials science, and energy storage. However, practical applications of ILs are often limited by their unfavorable physicochemical properties. Experimental screening becomes impractical due to the vast number of potential IL combinations. Therefore, the development of a robust and efficient model for predicting the IL properties is imperative. As the defining feature, it is of practice significance to establish an accurate yet efficient model to predict the normal melting point of IL (T m), which may facilitate the discovery and design of novel ILs for specific applications. In this study, we presented a pseudo-Siamese convolution neural network (pSCNN) inspired by SCNN and focused on the T m. Utilizing a data set of 3098 ILs, we systematically assess various deep learning models (ANN, pSCNN, and Transformer-CNF), along with molecular descriptors (ECFP fingerprint and Mordred properties), for their performance in predicting the T m of ILs. Remarkably, among the investigated modeling schemes, the pSCNN, coupled with filtered Mordred descriptors, demonstrates superior performance, yielding mean absolute error (MAE) and root-mean-square error (RMSE) values of 24.36 and 31.56 °C, respectively. Feature analysis further highlights the effectiveness of the pSCNN model. Moreover, the pSCNN method, with a pair of inputs, can be extended beyond ionic liquid melting point prediction.

Hydrogen mitigates brain injury by prompting NEDD4-CX43- mediated mitophagy in traumatic brain injury.

BACKGROUND: Hydrogen (H2) has emerged as a potential therapeutic intervention for traumatic brain injury (TBI). However, the precise mechanism underlying H2's neuroprotective effects in TBI remain incompletely understood. METHODS: TBI mouse model was induced using the controlled cortical impact (CCI) method, and a cell model was established by exposing astrocytes to lipopolysaccharide (LPS). Cell viability was detected by CCK-8 kits. Cell apoptosis was measured by flow cytometry. ELISA was used to detect cytokine quantification. Protein and gene expression was detected by western blot and RT-PCR analysis. Co-immunoprecipitation (CO-IP) were employed for protein-protein interactions. Morris water maze test and rotarod test were applied for TBI mice. RESULTS: H2 treatment effectively inhibited the LPS-induced cell injury and cell apoptosis in astrocytes. NEDD4 expression was increased following H2 treatment coupled with enhanced mitophagy in LPS-treated astrocytes. Overexpression of NEDD4 and down-regulation of connexin 43 (CX43) mirrored the protective effects of H2 treatment in LPS-exposed astrocytes. NEDD4 interacts CX43 to regulates the ubiquitinated degradation of CX43. While overexpression of CX43 reversed the protective effects of H2 treatment in LPS-exposed astrocytes. In addition, H2 treatment significantly alleviated brain injury in TBI mouse model. CONCLUSION: H2 promoted NEDD4-CX43 mediated mitophagy to protect brain injury induced by TBI, highlighting a novel pathway underlying the therapeutic effects of H2 in TBI.