Unveiling the Role of Water in Heterogeneous Photocatalysis of Methanol Conversion for Efficient Hydrogen Production.

Water molecules, which act as both solvent and reactant, play critical roles in photocatalytic reactions for methanol conversion. However, the influence of water on the adsorption of methanol and desorption of liquid products, which are two essential steps that control the performance in photocatalysis, has been well under-explored. Herein, we reveal the role of water in heterogeneous photocatalytic processes of methanol conversion on the platinized carbon nitride (Pt/C3N4) model photocatalyst. In situ spectroscopy techniques, isotope effects, and computational calculations demonstrate that water shows adverse effects on the adsorption of methanol molecules and desorption processes of methanol oxidation products on the surface of Pt/C3N4, significantly altering the reaction pathways in photocatalytic methanol conversion process. Guided by these discoveries, a photothermal-assisted photocatalytic system is designed to achieve a high solar-to-hydrogen (STH) conversion efficiency of 2.3 %, which is among the highest values reported. This work highlights the important roles of solvents in controlling the adsorption/desorption behaviours of liquid-phase heterogeneous catalysis.

Advances in the research and application of neurokinin-1 receptor antagonists. / 神经激肽1å—ä½“æ‹®æŠ—å‰‚çš„ç ”ç©¶ä¸Žåº”ç”¨è¿›å±•.

Recently, the substance P (SP)/neurokinin-1 receptor (NK-1R) system has been found to be involved in various human pathophysiological disorders including the symptoms of coronavirus disease 2019 (COVID-19). Besides, studies in the oncological field have demonstrated an intricate correlation between the upregulation of NK-1R and the activation of SP/NK-1R system with the progression of multiple carcinoma types and poor clinical prognosis. These findings indicate that the modulation of SP/NK-1R system with NK-1R antagonists can be a potential broad-spectrum antitumor strategy. This review updates the latest potential and applications of NK-1R antagonists in the treatment of human diseases and cancers, as well as the underlying mechanisms. Furthermore, the strategies to improve the bioavailability and efficacy of NK-1R antagonist drugs are summarized, such as solid dispersion systems, nanonization, and nanoencapsulation. As a radiopharmaceutical therapeutic, the NK-1R antagonist aprepitant was originally developed as radioligand receptor to target NK-1R-overexpressing tumors. However, combining NK-1R antagonists with other drugs can produce a synergistic effect, thereby enhancing the therapeutic effect, alleviating the symptoms, and improving patients quality of life in several diseases and cancers.

A highly susceptible hACE2-transgenic mouse model for SARS-CoV-2 research.

Several animal models have been used to assist the development of vaccines and therapeutics since the COVID-19 outbreak. Due to the lack of binding affinity of mouse angiotensin-converting enzyme II (ACE2) to the S protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), increasing the susceptibility of mice to SARS-CoV-2 infection was considered in several ways. Here, we generated a COVID-19 mouse model expressing human ACE2 (hACE2) under the control of the CAG promoter. Overexpression of hACE2 did not pose a significant effect on weight growth. After SARS-CoV-2 inoculation, mice showed obvious viral replication and production of inflammation within 7 days, with a gradual decrease in body weight until death. Virological testing found that the virus can replicate in the respiratory system, small intestine, and brain. Additionally, this mouse model was applied to compare two antibody drug candidates, the anti-RBD antibody (MW06) and the mouse CD24-conjugated anti-RBD antibody (mCD24-MW06). Differences in antiviral effects between these two antibodies can be demonstrated in this mouse model when a challenge dose that invalidates the anti-RBD antibody treatment was used. This study provided a new mouse model for studying SARS-CoV-2 pathogenesis and evaluating potential interventions.

Clinical Outcomes On Tubridge Flow Diverter in Treatmenting Intracranial Aneurysms: a Retrospective Multicenter Registry Study.

PURPOSE: In China, the application of nitinol Tubridge flow diverter (TFD) has become popular for treating intracranial aneurysms (IAs). In this study, we investigated the safety outcomes of the application of TFD for treating IAs in real-world scenarios. METHODS: We retrospectively analyzed aneurysms treated with TFD in 235 centers throughout China between April 2018 and April 2020. The primary endpoint was the event-free survival rate at 12 months, defined as the occurrence of morbidity (spontaneous rupture, intraparenchymal hemorrhage (IPH), ischemic stroke, and permanent cranial neuropathy) or death. Univariate and multivariate analyses were performed to assess the risk factors. A good outcome was defined as a modified Rankin Score (mRS) of 0-2. RESULTS: We included 1281 unruptured aneurysms treated with TFD. The overall neurological morbidity and death rates after 12 months were 5.4 and 2.8%, respectively. Ischemic strokes were the most common complication (4.2%, P < 0.001). Cranial neuropathy, IPH, and spontaneous rupture occurred in 0.3%, 0.3%, and 0.5% of aneurysms, respectively. Univariate and multivariate analyses indicated that the male gender, older age, larger aneurysm diameter, and aneurysm located on BA were the independent risk factors for neurologic events. Aneurysm located on BA was the independent risk factor for ischemic strokes. Most patients (1222) had access to the mRS, and 93.2% of them achieved good outcomes. CONCLUSION: Treatment of IAs with TFD was associated with low morbidity and mortality, most of which were ischemic events. Large posterior aneurysms might be associated with a higher complication rate. TRIAL REGISTRATION: Retrospectively registered.

Thrombectomy versus combined thrombolysis and thrombectomy in patients with large vessel occlusion and chronic kidney disease.

Background: Whether intravenous thrombolysis (IVT) should be bridged before mechanical thrombectomy (MT) remains uncertain in patients with large vessel occlusion (LVO) and chronic kidney disease (CKD). Methods: This research systematically enrolled every patient with both acute ischemic stroke (AIS) and CKD who received MT and fulfilled the criteria for IVT from January 2015 to December 2022. According to whether they underwent IVT, the patients were categorized into two cohorts: MT and combined IVT + MT. A binary logistic regression model was used to adjust for potential confounders, and propensity score matching analysis was used to assess the efficacy and safety of IVT in AIS patients with CKD who underwent MT. Results: A total number of 406 patients were ultimately included in this study, with 236 patients in the MT group and 170 in the combined group. After PSM, there were 170 patients in the MT group and 170 in the combined group, and the clinical characteristics between the two groups were well balanced. The MT + IVT group had better long-term functional outcomes than the MT group (35.9% versus 21.2%, P = 0.003) and more modified thrombolysis in cerebral infarction (mTICI) (2b-3) (94.1% versus 87.6%, P = 0.038), while no significant difference was found regarding symptomatic intracranial hemorrhage (sICH). In line with the results observed in the in the postmatched population, the logistic regression revealed that patients in the IVT + MT group demonstrated superior clinical outcomes (adjusted OR 0.440 [95% CI (0.267-0.726)], P = 0.001) in the prematched population. Conclusion: For LVO patients with CKD and indications for IVT, IVT bridging MT improves their prognosis compared with direct MT.

Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis.

Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation of fluid transport and immunosurveillance. Targeting lymphatic vessels has become a potent strategy for treating various human diseases. The presence of varying degrees of inflammation in joints of rheumatoid arthritis (RA) and osteoarthritis (OA), characterized by heightened infiltration of inflammatory cells, increased levels of inflammatory factors, and activation of inflammatory signaling pathways, significantly contributes to the disruption of cartilage and bone homeostasis in arthritic conditions. Increasing evidence has demonstrated the pivotal role of lymphatic vessels in maintaining joint homeostasis, with their pathological alterations closely associated with the initiation and progression of inflammatory joint diseases. In this review, we provide a comprehensive overview of the evolving knowledge regarding the structural and functional aspects of lymphatic vessels in the pathogenesis of RA and OA. In addition, we summarized the potential regulatory mechanisms underlying the modulation of lymphatic function in maintaining joint homeostasis during inflammatory conditions, and further discuss the distinctions between RA and OA. Moreover, we describe therapeutic strategies for inflammatory arthritis based on lymphatic vessels, including the promotion of lymphangiogenesis, restoration of proper lymphatic vessel function through anti-inflammatory approaches, enhancement of lymphatic contractility and drainage, and alleviation of congestion within the lymphatic system through the elimination of inflammatory cells. At last, we envisage potential research perspectives and strategies to target lymphatic vessels in treating these inflammatory joint diseases.

Improving antibody optimization ability of generative adversarial network through large language model.

Generative adversarial networks (GANs) have successfully generated functional protein sequences. However, traditional GANs often suffer from inherent randomness, resulting in a lower probability of obtaining desirable sequences. Due to the high cost of wet-lab experiments, the main goal of computer-aided antibody optimization is to identify high-quality candidate antibodies from a large range of possibilities, yet improving the ability of GANs to generate these desired antibodies is a challenge. In this study, we propose and evaluate a new GAN called the Language Model Guided Antibody Generative Adversarial Network (AbGAN-LMG). This GAN uses a language model as an input, harnessing such models' powerful representational capabilities to improve the GAN's generation of high-quality antibodies. We conducted a comprehensive evaluation of the antibody libraries and sequences generated by AbGAN-LMG for COVID-19 (SARS-CoV-2) and Middle East Respiratory Syndrome (MERS-CoV). Results indicate that AbGAN-LMG has learned the fundamental characteristics of antibodies and that it improved the diversity of the generated libraries. Additionally, when generating sequences using AZD-8895 as the target antibody for optimization, over 50% of the generated sequences exhibited better developability than AZD-8895 itself. Through molecular docking, we identified 70 antibodies that demonstrated higher affinity for the wild-type receptor-binding domain (RBD) of SARS-CoV-2 compared to AZD-8895. In conclusion, AbGAN-LMG demonstrates that language models used in conjunction with GANs can enable the generation of higher-quality libraries and candidate sequences, thereby improving the efficiency of antibody optimization. AbGAN-LMG is available at http://39.102.71.224:88/.

Cir-DNA Sequencing Revealed the Landscape of Extrachromosomal Circular DNA in Articular Cartilage and the Potential Roles in Osteoarthritis.

OBJECTIVE: Extrachromosomal circular DNA (eccDNA) has been shown to be involved in several physiological and pathological processes including immunity, inflammation, aging, and tumor. However, the expression of eccDNA in cartilage has not been reported until now. In this study, we aimed to investigate the landscape of eccDNA in articular cartilage and analyze the potential roles in osteoarthritis (OA). METHODS: The samples of articular cartilage were obtained from total knee arthroplasty (TKA) donors with OA. The mitochondrial DNA (mtDNAs) and the linear DNAs from chondrocytes of articular cartilage were removed. Then the eccDNAs were enriched for cir-DNA sequencing. After quality control evaluation, we systematically revealed the identified eccDNA data including size distribution, the size range, and sequence pattern. Moreover, we explored and discussed the potential roles of eccDNA in OA via motif analysis and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: The chondrocytes from OA cartilage contained an abundance of eccDNAs, which was termed as OC-eccDNAs (OA cartilage-derived eccDNA). The characteristics of OC-eccDNAs were tissue-specific, including the distribution, the size range, and sequence pattern. Moreover, the functional analysis indicated that eccDNA may be involved in the homeostasis maintenance of chondrocytes and participated in the process of OA. CONCLUSIONS: Our data first showed the landscape of eccDNA in articular cartilage and preliminarily indicated the potential roles of eccDNA in OA.

Research on data imbalance in intrusion detection using CGAN.

To address the problems of attack category omission and poor generalization ability of traditional Intrusion Detection System (IDS) when processing unbalanced input data, an intrusion detection strategy based on conditional Generative Adversarial Networks (cGAN) is proposed. The cGAN generates attack samples that approximately obey the distribution pattern of input data and are randomly distributed within a certain bounded interval, which can avoid the redundancy caused by mechanical data widening. The experimental results show that the strategy has better performance indexes and stronger generalization ability in overall performance, which can solve insufficient classification performance and detection omission caused by unbalanced distribution of data categories and quantities.

Titanium-Oxygen Clusters Brazing Li with Li6.5La3Zr1.5Ta0.5O12 for High-Performance All-Solid-State Li Batteries.

Garnet-based solid-state electrolytes are considered crucial candidates for solid-state Li batteries due to their high Li+ conductivity and nonflammability; however, poor interfacial contact with the Li anode and growth of Li dendrites limit their application. Herein, a high-activity titanium-oxygen cluster is used as a brazing filler to braze the Li6.5La3Zr1.5Ta0.5O12 (LLZTO) with an Li anode into the whole unit. The brazing layer leads to a significantly lower interfacial impedance of 8.32 Ω cm2. Furthermore, the brazing layer is an isotropic amorphous ion-electron hybrid conductive layer, which significantly promotes Li+ transport and regulates the distribution of the electric field, therefore inhibiting the growth of Li dendrites. The cell exhibits an ultrahigh critical current density of 2.3 mA cm-2 and stable cycling of over 4000 h at 0.5 mA cm-2 (25 °C).

Inhalation delivery of dexamethasone with iSEND nanoparticles attenuates the COVID-19 cytokine storm in mice and nonhuman primates.

Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2-challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases.

α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice.

Sepsis is one of the most fatal inflammatory diseases with multiple organ failure caused by pathological infection. α-Hederin, a monodesmosidic triterpenoid saponin, has many biological activities including anti-inflammation. This study aimed to investigate the effect of α-Hederin on lung and liver injuries in septic mice. Mice underwent cecal ligation and puncture-induced sepsis were intraperitoneally injected with 0.3 or 3 mg/kg α-Hederin. α-Hederin treatment dose-dependently attenuated the lung and liver injuries in septic mice. Correspondingly, α-Hederin significantly decreased malondialdehyde production, increased the levels of superoxide dismutase and glutathione in lung tissues, reduced serum alanine aminotransferase and aspartate aminotransferase activities, and suppressed the levels of TNF-α and IL-6 in both tissues and in the serum. Moreover, α-Hederin augmented CD206 level and inhibited the productions of CD86 and iNOS in lung and liver tissues of septic mice. Importantly, p-p65/p65 was suppressed, whereas IκB was elevated by α-Hederin. In conclusion, α-Hederin could improve the lung and liver injuries in mice with sepsis by regulating macrophage M1/M2 polarization and inhibiting the activation of NF-κB signaling pathway.

An mRNA-based T-cell-inducing antigen strengthens COVID-19 vaccine against SARS-CoV-2 variants.

Herd immunity achieved through mass vaccination is an effective approach to prevent contagious diseases. Nonetheless, emerging SARS-CoV-2 variants with frequent mutations largely evaded humoral immunity induced by Spike-based COVID-19 vaccines. Herein, we develop a lipid nanoparticle (LNP)-formulated mRNA-based T-cell-inducing antigen, which targeted three SARS-CoV-2 proteome regions that enriched human HLA-I epitopes (HLA-EPs). Immunization of HLA-EPs induces potent cellular responses to prevent SARS-CoV-2 infection in humanized HLA-A*02:01/DR1 and HLA-A*11:01/DR1 transgenic mice. Of note, the sequences of HLA-EPs are highly conserved among SARS-CoV-2 variants of concern. In humanized HLA-transgenic mice and female rhesus macaques, dual immunization with the LNP-formulated mRNAs encoding HLA-EPs and the receptor-binding domain of the SARS-CoV-2 B.1.351 variant (RBDbeta) is more efficacious in preventing infection of SARS-CoV-2 Beta and Omicron BA.1 variants than single immunization of LNP-RBDbeta. This study demonstrates the necessity to strengthen the vaccine effectiveness by comprehensively stimulating both humoral and cellular responses, thereby offering insight for optimizing the design of COVID-19 vaccines.

Development of highly effective LCB1-based lipopeptides targeting the spike receptor-binding motif of SARS-CoV-2.

LCB1 is a computationally designed 56-mer miniprotein targeting the spike (S) receptor-binding motif of SARS-CoV- 2 with high potent activity (Science, 2020; Cell host microbe, 2021); however, recent studies have demonstrated that emerging SARS-CoV-2 variants are highly resistant to LCB1's inhibition. In this study, we first identified a truncated peptide termed LCB1v8, which maintained the high antiviral potency. Then, a group of lipopeptides were generated by modifying LCB1v8 with diverse lipids, and of two lipopeptides, the C-terminally stearicacid-conjugtaed LCB1v17 and cholesterol-conjugated LCB1v18, were highly effective in inhibiting both S protein-pseudovirus and authentic SARS-CoV-2 infections. We further showed that LCB1-based inhibitors had similar α-helicity and thermostability in structure and bound to the target-mimic RBD protein with high affinity, and the lipopeptides exhibited greatly enhanced binding with the viral and cellular membranes, improved inhibitory activities against emerging SARS-CoV-2 variants. Moreover, LCB1v18 was validated with high preventive and therapeutic efficacies in K18-hACE2 transgenic mice against lethal SARS-CoV-2 challenge. In conclusion, our studies have provided important information for understanding the structure and activity relationship (SAR) of LCB1 inhibitor and would guide the future development of novel antivirals.

Dysregulation of glutamine/glutamate metabolism in COVID-19 patients: A metabolism study in African population and mini meta-analysis.

Coronavirus disease 2019 (COVID-19) remains a serious global threat. The metabolic analysis had been successfully applied in the efforts to uncover the pathological mechanisms and biomarkers of disease severity. Here we performed a quasi-targeted metabolomic analysis on 56 COVID-19 patients from Sierra Leone in western Africa, revealing the metabolomic profiles and the association with disease severity, which was confirmed by the targeted metabolomic analysis of 19 pairs of COVID-19 patients. A meta-analysis was performed on published metabolic data of COVID-19 to verify our findings. Of the 596 identified metabolites, 58 showed significant differences between severe and nonsevere groups. The pathway enrichment of these differential metabolites revealed glutamine and glutamate metabolism as the most significant metabolic pathway (Impact = 0.5; -log10P = 1.959). Further targeted metabolic analysis revealed six metabolites with significant intergroup differences, with glutamine/glutamate ratio significantly associated with severe disease, negatively correlated with 10 clinical parameters and positively correlated with SPO2 (rs = 0.442, p = 0.005). Mini meta-analysis indicated elevated glutamate was related to increased risk of COVID-19 infection (pooled odd ratio [OR] = 2.02; 95% confidence interval [CI]: 1.17-3.50) and severe COVID-19 (pooled OR = 2.28; 95% CI: 1.14-4.56). In contrast, elevated glutamine related to decreased risk of infection and severe COVID-19, the pooled OR were 0.30 (95% CI: 0.20-0.44), and 0.44 (95% CI: 0.19-0.98), respectively. Glutamine and glutamate metabolism are associated with COVID-19 severity in multiple populations, which might confer potential therapeutic target of COVID-19, especially for severe patients.

Role of introduced Se element and induced anion vacancies in Mo(SSe)2-x/G van der Waals heterostructure for enhanced hydrogen evolution reaction.

The Gibbs free energy of hydrogen adsorption at the edge of molybdenum disulfide (MoS2) is close to that of Pt, meaning that MoS2 is the best candidate to replace Pt-based materials. However, easy agglomeration between layers to mask active sites, lack of catalytic activity in the basal planes, and poor electronic conductivity make MoS2 exhibit dissatisfactory hydrogen evolution reaction (HER) catalytic performance. Here, we successfully construct a van der Waals heterostructure stacked alternately with Mo(SSe)2-x and graphene (Mo(SSe)2-x/G) to enhance its catalytic ability. The introduction of Se into MoS2 and the thermal treatment induce the sample to generate more anion vacancies. Theoretical and experimental results demonstrate the constructed van der Waals heterostructure, the introduced Se element, and the increased anion vacancies are in favor of promoting the number of active sites and improving the electronic conductivity of the catalyst. Therefore, Mo(SSe)2-x/G exhibits superior HER catalytic performance (the overpotentials of 137 mV and 136 mV at a current of 10 mA cm-2) and long-term stabilities (>90 h and 140 h at a current density of 20 mA cm-2) in both acidic and alkaline media.

Correction: A Truncated Receptor-Binding Domain of MERS-CoV Spike Protein Potently Inhibits MERS-CoV Infection and Induces Strong Neutralizing Antibody Responses: Implication for Developing Therapeutics and Vaccines.

[This corrects the article DOI: 10.1371/journal.pone.0081587.].

Vertebral arteriovenous fistulae (AVF) and vertebral artery aneurysms in neurofibromatosis type 1: A case report and a systematic review.

BACKGROUND: Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene on the long arm of chromosome 17, which affects the skin, nervous system, eyes, and skeleton system. Vertebral arteriovenous fistula (AVF) associated with neurofibromatosis type I (NF-1) is rare. CASE PRESENTATION: We report a 31-year-old postpartum woman with NF1 with vertebral arteriovenous fistulae (AVFs). She presented to our hospital because of neck pain, intracranial hypotension headache, and right upper limb weakness. She had a family history of NF1. After endovascular intervention, the AVF disappeared. However, a new aneurysm appeared on the right vertebral artery V5 dissection after 6 months of follow-up. CONCLUSIONS: The presence of NF1 in patients who present with neurologic signs should prompt further angiography. Awareness of the coexistence between NF1 and AVF or aneurysm is crucial to avoiding diagnostic delays. Endovascular occlusion of VV-AVF in NF-1 patients is effective and safe.

Exosomal Vaccine Loading T Cell Epitope Peptides of SARS-CoV-2 Induces Robust CD8+ T Cell Response in HLA-A Transgenic Mice.

Purpose: Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8+ T cell response. Methods: Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining. Results: The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-γ spot forming units and the frequencies of IFN-γ+/CD8+ T cells were 10-82-fold and 13-65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response. Conclusion: Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8+ T cell response in HLA-A transgenic mice.

MeCP2 inhibits ischemic neuronal injury by enhancing methylation of the FOXO3a promoter to repress the SPRY2-ZEB1 axis.

Methyl CpG binding protein 2 (MeCP2) is involved in nerve regeneration following ischemic stroke, but the related mechanism remains unclear. Here, we found low MeCP2 expression in hippocampal tissues. Using functional analysis, we demonstrated that MeCP2 accelerated FOXO3a methylation and subsequently inhibited its expression, thus repressing the apoptosis of neuronal cells. Mechanistically, FOXO3a could bind to the promoter region of SPRY2, consequently inducing its transcription and promoting the expression of the downstream target gene ZEB1. Altogether, our study revealed that overexpression of MeCP2 can protect mice against ischemic brain injury via disruption of the FOXO3a/SPRY2/ZEB1 signaling axis. Our results identify ectopic expression of MeCP2 as a therapeutic target in ischemic stroke.