Multiple early factors anticipate post-acute COVID-19 sequelae.

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.

Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.

WRKY transcription factors and OBERON histone-binding proteins form complexes to balance plant growth and stress tolerance.

WRKY transcription factors in plants are known to be able to mediate either transcriptional activation or repression, but the mechanism regulating their transcriptional activity is largely unclear. We found that group IId WRKY transcription factors interact with OBERON (OBE) proteins, forming redundant WRKY-OBE complexes in Arabidopsis thaliana. The coiled-coil domain of WRKY transcription factors binds to OBE proteins and is responsible for target gene selection and transcriptional repression. The PHD finger of OBE proteins binds to both histones and WRKY transcription factors. WRKY-OBE complexes repress the transcription of numerous stress-responsive genes and are required for maintaining normal plant growth. Several WRKY and OBE mutants show reduced plant size and increased drought tolerance, accompanied by increased expression of stress-responsive genes. Moreover, expression levels of most of these WRKY and OBE genes are reduced in response to drought stress, revealing a previously uncharacterized regulatory mechanism of the drought stress response. These results suggest that WRKY-OBE complexes repress transcription of stress-responsive genes, and thereby balance plant growth and stress tolerance.

INDETERMINATE1 autonomously regulates phosphate homeostasis upstream of the miR399-ZmPHO2 signaling module in maize.

The macronutrient phosphorus is essential for plant growth and development. Plants have evolved multiple strategies to increase the efficiency of phosphate (Pi) acquisition to protect themselves from Pi starvation. However, the crosstalk between Pi homeostasis and plant development remains to be explored. Here, we report that overexpressing microRNA399 (miR399) in maize (Zea mays) is associated with premature senescence after pollination. Knockout of ZmPHO2 (Phosphate 2), a miR399 target, resulted in a similar premature senescence phenotype. Strikingly, we discovered that INDETERMINATE1 (ID1), a floral transition regulator, inhibits the transcription of ZmMIR399 genes by directly binding to their promoters, alleviating the repression of ZmPHO2 by miR399 and ultimately contributing to the maintenance of Pi homeostasis in maize. Unlike ZmMIR399 genes, whose expression is induced by Pi deficiency, ID1 expression was independent of the external inorganic orthophosphate status, indicating that ID1 is an autonomous regulator of Pi homeostasis. Furthermore, we show that ZmPHO2 was under selection during maize domestication and cultivation, resulting in a more sensitive response to Pi starvation in temperate maize than in tropical maize. Our study reveals a direct functional link between Pi-deprivation sensing by the miR399-ZmPHO2 regulatory module and plant developmental regulation by ID1.

Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.

Foliar N2 O emissions constitute a significant source to atmosphere.

Nitrous oxide (N2 O) is a potent greenhouse gas and causes stratospheric ozone depletion. While the emissions of N2 O from soil are widely recognized, recent research has shown that terrestrial plants may also emit N2 O from their leaves under controlled laboratory conditions. However, it is unclear whether foliar N2 O emissions are universal across varying plant taxa, what the global significance of foliar N2 O emissions is, and how the foliage produces N2 O in situ. Here we investigated the abilities of 25 common plant taxa, including trees, shrubs and herbs, to emit N2 O under in situ conditions. Using 15 N isotopic labeling, we demonstrated that the foliage-emitted N2 O was predominantly derived from nitrate. Moreover, by selectively injecting biocide in conjunction with the isolating and back-inoculating of endophytes, we demonstrated that the foliar N2 O emissions were driven by endophytic bacteria. The seasonal N2 O emission rates ranged from 3.2 to 9.2 ng N2 O-N g-1 dried foliage h-1 . Extrapolating these emission rates to global foliar biomass and plant N uptake, we estimated global foliar N2 O emission to be 1.21 and 1.01 Tg N2 O-N year-1 , respectively. These estimates account for 6%-7% of the current global annual N2 O emission of 17 Tg N2 O-N year-1 , indicating that in situ foliar N2 O emission is a universal process for terrestrial plants and contributes significantly to the global N2 O inventory. This finding highlights the importance of measuring foliar N2 O emissions in future studies to enable the accurate assigning of mechanisms and the development of effective mitigation.

Studies on the Coordination Patterns of Diamine-Bridged Tetraphenoxy Ligands with Group 3 and 4 Metals.

Alkane elimination reactions between the diamino- and dianilino-bridged tetrakis(phenolate) proligands 1a,b-H4 and precursors M(CH2SiMe3)3(THF)2, M(CH2C6H4-o-NMe2)3 (M = Sc and Y), and Hf(CH2Ph)4 were investigated. The diamino-bridged 1a-H4 afforded nonsymmetric complex 2a-Y2 incorporating two metal centers in different coordination environments. This one and other dinuclear compounds 2b-Sc2, 2a-Hf2, and 2b-Hf2 were characterized by NMR spectroscopy, elemental analysis, and X-ray diffraction study (for 2a-Y2 and 2b-Sc2) and turned out to be symmetric in solution. Compound 2a-Y2, upon treatment with 2 equiv of 2-phenylpyridine, afforded symmetric bis(aryl) product 3a-Y2, which was authenticated by NMR spectroscopy and X-ray crystallography. The mechanism of its formation was studied by DFT computations and presumably involves a cooperative reorganization process within the nonsymmetric parent 2a-Y2 to afford a symmetric isomer prior to its reaction with 2-phenylpyridine.

Circular RNAs: emerging players in brain aging and neurodegenerative diseases.

Brain aging is closely related to neurodegenerative diseases. Circular RNAs (circRNAs) are a type of conserved RNAs with covalently closed continuous loops. Emerging evidence has shown that circRNAs are implicated in the biology of brain aging and the pathology of age-related neurodegenerative diseases. Here, we summarize current studies on circRNAs associated with brain aging and neurodegenerative diseases by discussing their expression features, pathophysiological roles, and mechanisms of action. We also discuss the potential challenges of circRNA-based therapy against brain aging and neurodegenerative diseases, as well as their potential as diagnostic biomarkers of neurodegenerative diseases. The review provides insights into current progress in the functions of circRNAs in the process of brain aging and neurodegenerative diseases. © 2022 The Pathological Society of Great Britain and Ireland.

Characterization of an autonomous pathway complex that promotes flowering in Arabidopsis.

Although previous studies have identified several autonomous pathway components that are required for the promotion of flowering, little is known about how these components cooperate. Here, we identified an autonomous pathway complex (AuPC) containing both known components (FLD, LD and SDG26) and previously unknown components (EFL2, EFL4 and APRF1). Loss-of-function mutations of all of these components result in increased FLC expression and delayed flowering. The delayed-flowering phenotype is independent of photoperiod and can be overcome by vernalization, confirming that the complex specifically functions in the autonomous pathway. Chromatin immunoprecipitation combined with sequencing indicated that, in the AuPC mutants, the histone modifications (H3Ac, H3K4me3 and H3K36me3) associated with transcriptional activation are increased, and the histone modification (H3K27me3) associated with transcriptional repression is reduced, suggesting that the AuPC suppresses FLC expression at least partially by regulating these histone modifications. Moreover, we found that the AuPC component SDG26 associates with FLC chromatin via a previously uncharacterized DNA-binding domain and regulates FLC expression and flowering time independently of its histone methyltransferase activity. Together, these results provide a framework for understanding the molecular mechanism by which the autonomous pathway regulates flowering time.

Risk factors and predictive model of cerebral edema after road traffic accidents-related traumatic brain injury.

PURPOSE: Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries. METHODS: This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q1, Q3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. RESULTS: According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 - 25.42, p = 0.002), 2.85 (95% CI: 1.11 - 7.31, p = 0.030), 2.62 (95% CI: 1.12 - 6.13, p = 0.027), 2.44 (95% CI: 1.25 - 4.76, p = 0.009), and 1.5 (95% CI: 1.10 - 2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ2 = 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ2 = 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. CONCLUSION: Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Effect of ranibizumab combined with laser photocoagulation in the treatment of diabetic macular edema.

Objective: To explore the clinical effect of ranibizumab combined with laser photocoagulation (LP) in treating diabetic macular edema (DME). Methods: We retrospectively reviewed the clinical data of 118 patients with DME admitted to The Affiliated Eye Hospital of Nanchang University from May 2021 to March 2023. Among them, 38 patients received LP alone (Laser-group), 39 patients received ranibizumab alone (Ranibizumab-group), and 41 patients received LP combined with ranibizumab (Combined-group). The improvement of macular edema (ME), visual acuity, and complications between the groups were compared. Results: The time of ME regression, exudation absorption and fundus hemorrhage absorption in the Combined-group was shorter than in the Laser-group and the Ranibizumab-group (P<0.05). After treatment, the CMT and RNV of the three groups decreased compared to pretreatment levels and were lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). BCVA increased after the treatment in all groups, and was markedly higher in the Combined-group than in the Laser and the Ranibizumab-groups (P<0.05). NO were higher in the Combined-group compared to the Laser-group and the Ranibizumab-group. The post-treatment VEGF levels decreased in all groups, and were significantly lower in the Combined-group compared to the Laser-group and the Ranibizumab-group (P<0.05). The incidence of complications in the Combined-group was lower than in the Laser-group and the Ranibizumab-group (P<0.05). Conclusions: Compared to ranibizumab or LP alone, ranibizumab combined with LP is more effective in reducing ME in patients with DEM, and is associated with fewer complications.

A Stapled Peptide Inhibitor Targeting the Binding Interface of N6-Adenosine-Methyltransferase Subunits METTL3 and METTL14 for Cancer Therapy.

METTL3, a primary methyltransferase catalyzing the RNA N6-methyladenosine (m6A) modification, has been identified as an oncogene in several cancer types and thus nominated as a potentially effective target for therapeutic inhibition. However, current options using this strategy are limited. In this study, we targeted protein-protein interactions at the METTL3-METTL14 binding interface to inhibit complex formation and subsequent catalysis of the RNA m6A modification. Among candidate peptides, RM3 exhibited the highest anti-cancer potency, inhibiting METTL3 activity while also facilitating its proteasomal degradation. We then designed a stapled peptide inhibitor (RSM3) with enhanced peptide stability and formation of the α-helical secondary structure required for METTL3 interaction. Functional and transcriptomic analysis in vivo indicated that RSM3 induced upregulation of programmed cell death-related genes while inhibiting cancer-promoting signals. Furthermore, tumor growth was significantly suppressed while apoptosis was enhanced upon RSM3 treatment, accompanied by increased METTL3 degradation, and reduced global RNA methylation levels in two in vivo tumor models. This peptide inhibitor thus exploits a mechanism distinct from other small-molecule competitive inhibitors to inhibit oncogenic METTL3 activity. Our findings collectively highlight the potential of targeting METTL3 in cancer therapies through peptide-based inhibition of complex formation and proteolytic degradation.

Cation-π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles.

As an important noncovalent interaction, cation-π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-π interaction could serve as a major driving force to trigger peptide folding, resultant ß-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.

Current advances in the anti-inflammatory effects and mechanisms of natural polysaccharides.

Inflammatory bowel disease (IBD) is a chronic, multifactorial and inflammatory disease occurring in the colon tract. Bioactive polysaccharides from natural resources have attracted extensive attention due to their safety, accessibility and good bioactivities. In recent years, a variety of natural bioactive polysaccharides have been proven to possess anti-inflammatory effects on treating acute colitis. The objective of this review was to give an up-to-date review on the anti-inflammatory effects and mechanisms of natural polysaccharides on acute colitis. The anti-inflammatory effects of natural polysaccharides on acute colitis concerning clinical symptoms amelioration, colon tissue repairment, anti-oxidative stress alleviation, anti-inflammation, immune regulation, and gut microbiota modulation were comprehensively summarized. In addition, inducible murine models for assessing the anti-inflammatory effects of natural polysaccharides on acute colitis were also concluded. This review will offer the comprehensive understanding of anti-inflammatory mechanisms of natural polysaccharides in acute colitis, and render theoretical basis for the development and application of natural polysaccharides in drug and functional food.

Synthesis of Mono- and Dinuclear Aluminum Complexes Bearing Aromatic Amino-Phenolato Ligands: A Comparative Study in the Ring-Opening Polymerization of Cyclohexene Oxide.

Dinuclear aluminum methyl complexes bearing aromatic diamine-bridged tetra(phenolato) ligands and the mononuclear aluminum methyl complex with the phenylamine-bridged bis(phenolato) ligand have been synthesized and characterized. Structure determination revealed that the Al-Al distances in these dinuclear aluminum complexes are tunable by the choice of the suitable aromatic backbone of the diamine-bridged tetra(phenolato) ligands. The catalytic behaviors of these mono- and dinuclear aluminum complexes for cyclohexene oxide (CHO) polymerization were investigated. The activities of these dinuclear Al complexes were observed to increase with the decrease of Al-Al distances, and the dinuclear Al complexes appeared to have better catalytic activity than the mononuclear Al complex, even if the Al-Al distance is as long as 9.401 Å. Dinuclear aluminum complex 2, with the shortest Al-Al distance (7.236 Å), showed the highest activity toward CHO polymerization with TOFs up to 6460 h-1 in neat CHO at 30 °C. Furthermore, comparative kinetic studies revealed that the polymerization is first-order for CHO concentration, and the reaction orders for initiator concentration are different for the mono- and dinuclear Al complexes. The polymerization mechanism study revealed that both the methyl and phenolate groups were involved in the initiation process.

Experiences of visiting female sex workers, social interaction, support and HIV infection among elderly men from rural China.

OBJECTIVES: To make clear the roles of social interaction and social support in HIV infection among elderly men who visit female sex workers (FSW). METHODS: We conducted a case-control study: 106 newly HIV (+) vs. 87 HIV (-) elderly men who visited FSW with similar age, education levels, marital statuses, monthly expenses for entertainment and migration experiences. Experiences of visiting FSW, social interaction, and intimate social support were obtained. Backward binary logistic regression was applied. RESULTS: Cases' first visit to FSW happened at the age of 44.01 ± 12.25, older than controls (33.90 ± 13.43). 23.58% cases had gotten HIV-related health education (HRHE) before, less than controls (57.47%). More cases (48.91%) "always" got material support than controls (34.25%). Less cases gave "close" (38.04%) comments toward daily life, "satisfied" (34.78%) with their sexual life, "agree" being emotional fulfilled (46.74%) than controls (71.23% ,64.38%, and 61.64%). Risky factors for HIV infection among elderly men were having 3000 YUAN and above monthly income, visiting teahouse with friends, living without spouses, visiting different FSW, visiting FSW for other reason, receiving material support from most intimate sexual partner, older age of first visit to FSW. The protective factors were receiving HRHE, visiting FSW due to loneliness, and giving positive comments toward daily life with most intimate sexual partner. CONCLUSIONS: Elderly men's social interactions are mainly visiting teahouse which is a potential sexual venue. Getting HRHE is formal protective social interactions but very rare for cases (23.58%). Social support from sexual partner is not enough. Emotional support is protective meanwhile material support only is risky for becoming HIV-positive.

Complexation of Apigenin and Oxymatrine Leading to Enhanced Anti-inflammatory Activity.

Apigenin (APG) is a well-known dietary flavonoid with multiple bioactivities, but its poor aqueous solubility may result in low oral bioavailability and thus compromised therapeutic effects. In the present study, APG was complexed with oxymatrine (OMT), a natural quinolizidine alkaloid, for enhanced anti-inflammatory activity, and the related mechanisms in the interaction of APG with OMT were investigated. Fourier transform-infrared spectroscopy, fluorescence spectroscopy, Raman spectroscopy, and proton nuclear magnetic resonance spectroscopy characterizations demonstrated the occurrence of an APG-OMT complex formed at a molar ratio of 1:2. Then, molecular dynamics simulations and quantum chemical calculations were utilized to elucidate that hydrogen bonding, van der Waals forces, and hydrophobic effects were the main forces acting in the formation of the APG-OMT complex. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of APG in the APG-OMT complex was significantly higher than that of APG alone. Finally, bioactivity evaluation in the lipopolysaccharide-induced acute inflammatory injury mouse models showed that the APG-OMT complex exhibited more potent anti-inflammatory effects than APG alone. This study confirmed that APG and OMT exerted enhanced anti-inflammatory effects through self-complexation, which may provide a novel strategy for improving the bioavailability and bioactivity of natural product mixtures.

Systematic characterization of components of Makyo-kanseki-to granule and serum metabolomics for exploring its protective mechanism against acute lung injury in lipopolysaccharide-induced rats.

Makyo-kanseki-to has been used for the treatment of pneumonia, becoming a basic formula for coronavirus disease 2019. However, the chemical profile of Makyo-kanseki-to granule and its possible mechanism against acute lung injury from terminal metabolic regulation have been unclear. The aim of this study was to characterize the constituents in Makyo-kanseki-to granule and reveal the potential related mechanism of Makyo-kanseki-to granule treatment for acute lung injury using a rat model of lipopolysaccharide-induced acute lung injury. Totally, 78 constituents were characterized based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Makyo-kanseki-to granule could alleviate acute lung injury through modulating rectal temperature, pulmonary edema, histopathology, and processes of inflammatory and oxidative stress. Twenty-two potential biomarkers in acute lung injury rats were identified by metabolomics based on ultra-performance liquid chromatography coupled with quadrupole exactive high-field mass spectrometry. They were mainly involved in amino acids and glycerophospholipid metabolism, which were regulated by Makyo-kanseki-to granule. The present results not only increase the understanding of the chemical profile and molecular mechanism of Makyo-kanseki-to granule mediated protection against acute lung injury but also provide an experimental basis and new ideas for further development and clinical application of Makyo-kanseki-to granule.

Deficiency of astrocyte CysLT1R ameliorates depression-like behaviors in mice by modulating glutamate synaptic transmission.

Our previous study suggests that hippocampal cysteinyl leukotriene receptor 1 (CysLT1R) could be involved in depression. Herein we hypothesize that CysLT1R may regulate depression by affecting synaptic glutamate cycling based on existence of CysLT1R in the astrocytes that participate in occurrence of depression. We found that CysLT1R expression was significantly increased in the astrocyte of chronic unpredictable mild stress (CUMS)-induced depression-like mice, CysLT1R astrocyte-specific conditional knockout (AcKO) significantly improved depression-like behaviors, as indicated by decreased immobility time in the forced swimming test and tail suspension test and increased sucrose preference in the sucrose preference test, and knockdown of CysLT1R in the astrocyte of dentate gyrus (DG), the region with the most significant increase of CysLT1R in the astrocyte of depression-like mice, produced similar effects. Correspondingly, overexpression of CysLT1R in the astrocyte of DG induced depression-like behaviors in mice. The further study showed that CysLT1R AcKO ameliorated synaptic plasticity impairment, as reflected by increased synapse, LTP and PSD95, and promoted glutamate transporter 1 (GLT-1) expression by inhibiting NF-κB p65 nuclear translocation mediated by ß-arestin2 and clatrhin, subsequently decreased glutamate in synaptic cleft and GluN2B on postsynaptic membrane in depression-like mice. The present study also showed that GLT-1 agonist or NF-κB inhibitor ameliorated depressive-like behaviors induced by overexpression of the astrocyte CysLT1R of DG. Our study demonstrated that astrocyte CysLT1R regulated depression by modulating glutamate synaptic transmission, suggesting that CysLT1R could be a potential target for developing novel drugs of anti-depression.