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| 1 | Latitudinal pattern and the driving factors of leaf functional traits in 185 shrub species across eastern China显示文摘Aims To explore the pattern of the leaf functional traits of shrub species along a latitudinal gradient in eastern China and determine the driv-ing factors of leaf trait variation at a large scale.Methods We investigated the leaf thickness(LT),leaf area(LA),specific leaf area(SLA)and leaf dry mass content(LDMC)of 185 shrub species from 13 sites across eastern China.The trends of these four-leaf traits were ana-lyzed with respect to latitude,and the differences between different life forms(e.g.,evergreen and deciduous)and habitats(e.g.,understory and typical)were compared.We quantified the effects of the plant life forms and environmental factors on the leaf traits via mixed-model analyses.Important Findings The LT and LA decreased,whilst and the LDMC increased,as the latitude increased,and significant differences in these traits were observed between the different plant life forms.The LT and LA were smaller,whereas the SLA and LDMC were larger in decidu-ous shrubs than in evergreen shrubs.Among the different habitats,the LA and SLA were larger,while the LDMC was smaller in under-story shrubs than in typical shrub species.These results indicate that typical shrub species are better adapted to drier environments,as indicated by a reduced LT and increased LDMC.Furthermore,general linear models showed that variations in the four-leaf traits with respect to latitude were mainly caused by a shift in plant life forms. | Yongkai Luo Huifeng Hu Mengying Zhao He Li Shangshi Liu Jingyun Fang | 2019 | Journal of Plant Ecology2019，12，1： | 7 |
| 2 | Gallic acid inhibits fibroblast growth and migration in keloids through the AKT/ERK signaling pathway显示文摘Keloids are a fibroproliferative disorder of the skin resulted from abnormal healing of injured or irritated skin and are characterized by the ability to spread beyond the original boundary of the wound.Here,we tested the effect of gallic acid (GA),a plant polyphenol with selective growth inhibitory effects in cancer,on the proliferation and invasion of keloid fibroblasts (KFs)isolated from patients undergoing surgery.GA inhibited KF proliferation,migration,and invasion in parallel with the downregulation of matrix metalloproteinase-1 and -3 and upregulation of tissue inhibitors of metalloproteinase-1.Flow cytometric analysis showed that GA inhibited cell cycle progression and induced apoptosis.The effects of GA on KFs occurred in parallel with the inhibition of AKT and ERK1/2,suggesting that GA acts by suppressing the AKT/ERK signaling pathway.In ex vivo explant cultures of keloid tissues,GA inhibited the migration of KFs to the wound area and suppressed the expression of angiogenic markers concomitant with the inhibition of collagen deposition.These results identify GA as a potential therapeutic agent for the treatment of keloids and suggest a potential mechanism underlying its protective effect. | Xiuxia Wang Ke Liu Mengying Ruan Jun Yang Zhen Gao | 2018 | Acta Biochimica et Biophysica Sinica2018，50，11： | 6 |
| 3 | Meso-Cenozoic Evolution of Earth Surface System under the East Asian Tectonic Superconvergence显示文摘The East Asian geological setting has a long duration related to the superconvergence of the Paleo-Asian, Tethyan and Paleo-Pacific tectonic domains. The Triassic Indosinian Movement contributed to an unified passive continental margin in East Asia. The later ophiolites and I-type granites associated with subduction of the Paleo-Pacific Plate in the Late Triassic, suggest a transition from passive to active continental margins. With the presence of the ongoing westward migration of the Paleo-Pacific Subduction Zone, the sinistral transpressional stress field could play an important role in the intraplate deformation in East Asia during the Late Triassic to Middle Jurassic, being characterized by the transition from the E-W-trending structural system controlled by the Tethys and Paleo-Asian oceans to the NE-trending structural system caused by the Paleo-Pacific Ocean subduction. The continuously westward migration of the subduction zones resulted in the transpressional stress field in East Asia marked by the emergence of the Eastern North China Plateau and the formation of the Andean-type active continental margin from late Late Jurassic to Early Cretaceous(160-135 Ma), accompanied by the development of a small amount of adakites. In the Late Cretaceous(135-90 Ma), due to the eastward retreat of the Paleo-Pacific Subduction Zone, the regional stress field was replaced from sinistral transpression to transtension. Since a large amount of late-stage adakites and metamorphic core complexes developed, the Andean-type active continental margin was destroyed and the Eastern North China Plateau started to collapse. In the Late Cretaceous, the extension in East Asia gradually decreased the eastward retreat of the Paleo-Pacific subduction zones. Futhermore, a significant topographic inversion had taken place during the Cenozoic that resulted from a rapid uplift of the Tibet Plateau resulting from the India-Eurasian collision and the formation of the Bohai Bay Basin and other basins in the East Asian continental margin. The inversion caused a remarkable eastward migration of deformation, basin formation and magmatism. Meanwhile, the basins that mainly developed in the Paleogene resulted in a three-step topography which typically appears to drop eastward in altitude. In the Neogene, the basins underwent a rapid subsidence in some depressions after basin-controlled faulting, as well as the intracontinental extensional events in East Asia, and are likely to be a contribution to the uplift of the Tibetan Plateau. | DMITRIENKO Liudmila V. WANG Pengcheng LI Sanzhong CAO Xianzhi Ian SOMERVILLE ZHOU Zaizheng HU Mengying SUO Yanhui GUO Lingli WANG Yongming LI Xiyao LIU Xin YU Shengyao ZHU Junjiang | 2018 | Acta Geologica Sinica(English Edition)2018，92，2： | 6 |
| 4 | Nuclear Aurora kinase A switches m^(6)A reader YTHDC1 to enhance an oncogenic RNA splicing of tumor suppressor RBM4显示文摘Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression,yet how this process is regulated by oncogenic signal remains largely unknown.Here,we unveil that non-canonical activation of nuclear AURKA promotes an oncogenic RNA splicing of tumor suppressor RBM4 directed by m^(6)A reader YTHDC1 in lung cancer.Nuclear translocation of AURKA is a prerequisite for RNA aberrant splicing,specifically triggering RBM4 splicing from the full isoform(RBM4-FL)to the short isoform(RBM4-S)in a kinase-independent manner. | SiSi Li YangFan Qi JiaChuan Yu YuChao Hao Bin He MengJuan Zhang ZhenWei Dai TongHui Jiang SuYi Li Fang Huang Ning Chen Jing Wang MengYing Yang DaPeng Liang Fan An JinYao Zhao WenJun Fan YuJia Pan ZiQian Deng YuanYuan Luo Tao Guo Fei Peng ZhiJie Hou ChunLi Wang FeiMeng Zheng LingZhi Xu Jie Xu QingPing Wen BiLian Jin Yang Wang Quentin Liu | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 4 |
| 5 | Heat Exchanger Network Retrofit of Diesel Hydrotreating Unit Using Pinch Analysis显示文摘Diesel hydrotreating unit(DHT)is an integral part of the refinery,and its energy-saving optimization is of great significance to the enterprise.In this paper,process simulation software and energy management software are used to simulate the flowsheet and analyze the energy consumption,respectively.Stream data obtained from an existing DHT are applied in the pinch analysis for retrofitting the heat exchanger network(HEN)to achieve maximum energy utilization by using pinch analysis.Since DHT is constrained by pressure,the pressure factor is considered in the process of retrofitting.The results show that the amount of cross-pinch heat transfer is reduced,the inlet temperature of the furnace is increased by 55℃,and the amount of hot and cold utilities can be reduced by 70.25%and 50.16%,respectively.The economic evaluation indicates that the operating cost is saved by 4.39×10^(6)$/a,and the payback period is about 2 months. | Sun Mengying Zhang Fengjiao Liu Xinglong Sun Lanyi | 2021 | China Petroleum Processing & Petrochemical Technology2021，23，2： | 2 |
| 6 | SbMYB3 transcription factor promotes root-specific f lavone biosynthesis in Scutellaria baicalensis显示文摘Scutellaria baicalensis Georgi produces abundant root-specific f lavones(RSFs),which provide various benefits to human health.We have elucidated the complete biosynthetic pathways of baicalein and wogonin.However,the transcriptional regulation of f lavone biosynthesis in S.baicalensis remains unclear.We show that the SbMYB3 transcription factor functions as a transcriptional activator involved in the biosynthesis of RSFs in S.baicalensis.Yeast one-hybrid and transcriptional activation assays showed that SbMYB3 binds to the promoter of flavone synthase II-2(SbFNSII-2)and enhances its transcription.In S.baicalensis hairy roots,RNAi of SbMYB3 reduced the accumulation of baicalin and wogonoside,and SbMYB3 knockout decreased the biosynthesis of baicalein,baicalin,wogonin,and wogonoside,whereas SbMYB3 overexpression enhanced the contents of baicalein,baicalin,wogonin,and wogonoside.Transcript profiling by qRT–PCR demonstrated that SbMYB3 activates SbFNSII-2 expression directly,thus leading to more abundant accumulation of RSFs.This study provides a potential target for metabolic engineering of RSFs. | Yumin Fang Jie Liu Minmin Zheng Sanming Zhu Tianlin Pei Mengying Cui Lijing Chang Hanwen Xiao Jun Yang Cathie Martin Qing Zhao | 2023 | Horticulture Research2023，10，2： | 2 |
| 7 | Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms显示文摘Heart failure is the leading cause of death worldwide.Compound Danshen Dripping Pill(CDDP)or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China.However,the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown.We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E(ApoE)and LDL receptor(LDLR)dual deficient(ApoE^(–/–)LDLR^(–/–))mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure.CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis.Mechanistically,both Wnt and lysine-specific demethylase 4A(KDM4A)pathways were significantly activated in mice with heart injury.Conversely,CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors.While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity.In addition,CDDP attenuated simvastatin-induced myolysis in skeletal muscle.Taken together,our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure. | Yanfang Yang Ke Feng Liying Yuan Yuxin Liu Mengying Zhang Kaimin Guo Zequn Yin Wenjia Wang Shuiping Zhou He Sun Kaijing Yan Xijun Yan Xuerui Wang Yajun Duan Yunhui Hu Jihong Han | 2023 | Acta Pharmaceutica Sinica B2023，13，3： | 2 |
| 8 | Effect of Land Use on Soil Properties in Debris Flow Bottomland:A Case Study at Xiaojiang Basin, Yunnan显示文摘In order to understand the effect of different land use on soil physics and nutrients properties of the debris flow bottomland, a case study at Daqing gully (in Xiaojiang Basin, Yunnan) was conducted in 2004. Soil samples were taken at depth of 0-10,10-20,20-40,40-60,60-80 cm under three land use patterns crop bottomland(CL), forest bottomland(FL), and barren bottomland(BL). The results showed that the developing bottomland to CL promoted soil toaccumulate total phosphorus (TP) and available phosphorus (AP), pH value transferred from neutral to alkalescency, and organic matter decreased significantly. Furthermore, the contents of total nitrogen (TN) and available nitrogen (AN) in CL were lower than that of FL and BL because the growth of crops consumed more nutrients in soil. The results also showed that the contents of TP, AP and available potassium (AK) in soil were positively correlated with soil particle. | ZHANG Qiuying LI Fadong LIU Mengy SONG Xianfang OU Guoqiang | 2006 | Wuhan University Journal of Natural Sciences2006，11，4： | 2 |
| 9 | Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function显示文摘Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive behaviors.Sirt6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic enzymes.The aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp recordings.In addition,we evaluated cognition via a comprehensive set of behavioral tests.Compared with controls,Sirt6 was significantly decreased(P<0.05) in the PrL after CSD,accompanied by cognitive deficits and decreased FC between the PrL and accumbens nucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and cerebellum.Sirt6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced FC.Our analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 expression.Furthermore,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal neurons.These data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic neurotransmission.Thus,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases. | Jinpiao Zhu Chang Chen Zhen Li Xiaodong Liu Jingang He Ziyue Zhao Mengying He Binbin Nie Zili Liu Yingying Chen Kuanpin Su Xiang Li Juxiang Chen Hongbing Xiang Fuqiang Xu Kangguang Lin Zongze Zhang Jie Wang | 2023 | Neural Regeneration Research2023，18，11： | 1 |
| 10 | Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000显示文摘 | Li Liu Hope L Johnson Simon Cousens Jamie Perin Susana Scott Joy E Lawn Igor Rudan Harry Campbell Richard Cibulskis Mengying Li Colin Mathers Robert E Black | 2012 | The Lancet2012，，9832： | 1 |
| 11 | Overexpression of the mTERT gene by adenoviral vectors promotes the proliferation of neuronal stem cells in vitro and stimulates neurogenesis in the hippocampus of mice显示文摘We sought to construct the adenoviral vector carrying the gene encoding mouse telomerase reverse transcriptase(mTERT),as well as detect its expression and effect on the proliferation of neuronal stem cells.mTERT was am-plified by RT-PCR and then the eukaryotic expression vector of pDC-EGFP-TERT was constructed.After DNA sequence analysis,we detected that there were 293 cells transfected with pDC-EGFP-TERT and helper adenovirus plasmid pBHG lox ΔE1,and three Cre using Lipofectamine 2000 mediation,named Ad-mTERT-GFP,to pack-age adenoviral particles.The Ad-mTERT-GFP was used to infect neuronal stem cells and then the expression and activity of mTERT were detected.In addition,Bromodeoxyuridine labeling test identified the impact of mTERT overexpression on proliferation of neuronal stem cells.The recombinant adenoviral vector confirmed that mTERT was successfully constructed.Overexpression of mTERT stimulated the proliferation of neuronal stem cells both in vitro and in vivo.mTERT overexpression via adenoviral vector carrying mTERT cDNA upregulated the ability of proliferation in neuronal stem cells. | Mengying Liu Yao Hu Lijuan Zhu Chen Chen Yu Zhang Weixiang Sun Qigang Zhou | 2012 | The Journal of Biomedical Research2012，26，5： | 1 |
| 12 | New insights from the widening homogeneity perspective to target intratumor heterogeneity显示文摘Precision medicine has shed new light on the treatment of heterogeneous cancer patients.However,intratumor heterogeneity strongly constrains the clinical benefit of precision medicine.Thus,rethinking therapeutic strategies from a different facet within the precision medicine framework will not only diversify clinical interventions,but also provide an avenue for precision medicine.Here,we explore the current approaches for targeting intratumor hetero-geneity and their limitations.Furthermore,we propose a theoretical strategy with a“homogenization”feature based on iatrogenic evolutionary selection to target intratumor heterogeneity. | Mengying Tong Ziqian Deng Xiaolong Zhang Bin He Mengying Yang Wei Cheng Quentin Liu | 2018 | Cancer Communications2018，38，1： | 1 |
| 13 | Virus-like particle vaccine by intranasal vaccination elicits protective immunity against respiratory syncytial viral infection in mice显示文摘呼吸 syncytial 病毒(RSV ) 是在婴儿和孩子的更低的呼吸感染的一个领先的原因,但是仍然没有可得到的准许的疫苗。在这份报告,我们基于 Bac-to-Bac baculovirus 表达式系统开发了像病毒的粒子(VLP ) 疫苗,由一个流行性感冒病毒矩阵(M1 ) 组成蛋白质和 RSV 熔化蛋白质(F) 或 glycoprotein (G) 。这些 RSV VLP 被西方的污点分析和电子显微镜学识别。有 RSV-F VLP, RSV-G VLP,或两个的 intranasally 使免疫的女 BALB/c 老鼠(i.n ) 对 RSV 显示出病毒特定的抗体回答。全部的 IgG, IgG1, IgG2a,和 mucosal IgA 与 RSV-F 正 RSV-G VLP 在老鼠被检测,揭示细胞的有势力和 mucosal 免疫者回答。而且,我们发现这些混合 RSV VLP 对实时 RSV 挑战授与提高的保护,在病毒的复制和组织病理学说的变化的明显的变细与病毒的感染联系了的肺的出现重要减少。这些结果证明由 intranasal 种痘的 RSV-F 正 RSV-G VLP 是保证使用棉花老鼠和首领模型的进一步的评估的一个有希望的疫苗的候选人。 | Mengying Cai Cheng Wang Yufeng Li Hongjing Gu Sujing Sun Yueqiang Duan Chengcai Lai Keyu Wang Xiaolan Yang Li Xing Peirui Zhang Zhaohai Wang Shaogeng Zhang Xiaodong Guo Shubing Liu Yigang Tong Xiliang Wang Penghui Yang | 2017 | Acta Biochimica et Biophysica Sinica2017，49，1： | 1 |
| 14 | Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000显示文摘 | Li Liu Hope L Johnson Simon Cousens Jamie Perin Susana Scott Joy E Lawn Igor Rudan Harry Campbell Richard Cibulskis Mengying Li Colin Mathers Robert E Black | 2012 | The Lancet2012，，9832： | 1 |
| 15 | Near-infrared dyes, nanomaterials and proteins显示文摘Taking the advantage of reduced scattering and low autofluorescence background, the NIR fluorescence probes, such as fluorescence proteins, organic molecules and nanoparticles, not only hold the promise of in vivo imaging of biological processes in physiology and pathology with high signal-to-noise ratio, but also for clinical diagnosis. In this review, we provide an overview of the recent progress on NIR probes,focusing on fundamental mechanisms of NIR dyes and nanoparticles, and protein engineering strategies for NIR proteins. | Zong Chang Feng Liu Liang Wang Mengying Deng Chunhua Zhou Qinchao Sun Jun Chu | 2019 | Chinese Chemical Letters2019，30，10： | 1 |
| 16 | iRGD-reinforced, photo-transformable nanoclusters toward cooperative enhancement of intratumoral penetration and antitumor efficacy显示文摘Insufficient intratumoral penetration greatly hurdles the anticancer performance of nanomedicine. To realize highly efficient tumor penetration in a precisely and spatiotemporally controlled manner, far-red light-responsive nanoclusters (NCs) capable of size shrinkage and charge conversion were developed and co-administered with iRGD to synergistically improve the intratumoral penetration and the anticancer efficacy. The NCs were constructed using the singlet oxygen-sensitive (SOS) polyethylene glycolpolyurethane-polyethylene glycol (PEG-(1O2)PU-PEG) triblock copolymer to encapsulate the doxorubicin (DOX)-loaded, chlorin e6 (Ce6)-conjugated polyamindoamine (PAMAM) dendrimer (DCD) via the double-emulsion method. Co-administration of iRGD notably increased the permeability of NCs within tumor vasculature and tumor tissues. In addition, upon far-red light irradiation (660 nm) of tumors at low optical density (10 mW/cm2), the generated 1O2 could disintegrate the NCs and release the DCD with positive surface charge and ultra-small size (~ 5 nm), which synergized with iRGD to enable deep intratumoral penetration. Consequently, the local 1O2 at lethal concentrations along with the released DOX efficiently and cooperatively eradicated tumor cells. This study provides a convenient approach to spatiotemporally promote the intratumoral penetration of nanomedicine and mediate programmed anticancer therapy. | Jing Yan Rongying Zhu Fan Wu Ziyin Zhao Huan Ye Mengying Hou Yong Liu Lichen Yin | 2020 | Nano Research2020，13，10： | 1 |
| 17 | HIF1α epigenetically repressed macrophages via CRISPR/Cas9-EZH2 system for enhanced cancer immunotherapy显示文摘Immune suppressive microenvironment in tumor emerges as the main obstacle for cancer immunotherapy.In this study,we identified that HIF1α was activated in the tumor associated macrophages and acted as an important factor for the immune suppressive microenvironment.Epigenetically silencing of Hif1αvia histone H3 methylation in the promoter region was achieved by CRISPR/dCas9-EZH2 system,in which histone H3 methylase EZH2 was recruited to the promoter region specifically.The Hif1αsilenced macrophage,namely HERM(Hif1αEpigenetically Repressed Macrophage)manifested as inheritable tumor suppressing phenotype.In the subcutaneous B16-F10 melanoma syngeneic model,intratumoral injection of HERMs reprogrammed the immune suppressive microenvironment to the active one,reducing tumor burden and prolonging overall survival.Additionally,HERMs therapy remarkably inhibited tumor angiogenesis.Together,our study has not only identified a promising cellular and molecular target for reverting immune suppressive microenvironment,but also provided a potent strategy for reprogramming tumor microenvironment via epigenetically reprogrammed macrophages. | Yan Dong Siyan Zhang Xiaotong Gao Dandan Yin Tingting Wang Zhelong Li Zhuo Wan Mengying Wei Ying Luo Guodong Yang Li Liu | 2021 | Bioactive Materials2021，6，9： | 1 |
| 18 | Hydroxyl radical-involved cancer therapy via Fenton reactions显示文摘The tumor microenvironment features over-expressed hydrogen peroxide(H_(2)O_(2)).Thus,versatile therapeutic strategies based on H_(2)O_(2) as a reaction substrate to generate hydroxyl radical(•OH)have been used as a prospective therapeutic method to boost anticancer efficiency.However,the limited Fenton catalysts and insufficient endogenous H_(2)O_(2) content in tumor sites greatly hinder•OH production,failing to achieve the desired therapeutic effect.Therefore,supplying Fenton catalysts and elevating H_(2)O_(2) levels into cancer cells are effective strategies to improve•OH generation.These therapeutic strategies are systematically discussed in this review.Furthermore,the challenges and future developments of hydroxyl radical-involved cancer therapy are discussed to improve therapeutic efficacy. | Mengying Liu Yun Xu Yanjun Zhao Zheng Wang Dunyun Shi | 2022 | Frontiers of Chemical Science and Engineering2022，16，3： | 1 |
| 19 | Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000显示文摘 | Li Liu Hope L Johnson Simon Cousens Jamie Perin Susana Scott Joy E Lawn Igor Rudan Harry Campbell Richard Cibulskis Mengying Li Colin Mathers Robert E Black | 2012 | The Lancet . 2012 (9832)2012，，9832： | 1 |
| 20 | CB1R-stabilized NLRP3 inflammasome drives antipsychotics cardiotoxicity显示文摘Long-term use of antipsychotics is a common cause of myocardial injury and even sudden cardiac deaths that often lead to drug withdrawn or discontinuation.Mechanisms underlying antipsychotics cardiotoxicity remain largely unknown.Herein we performed RNA sequencing and found that NLRP3 inflammasome-mediated pyroptosis contributed predominantly to multiple antipsychotics cardiotoxicity.Pyroptosis-based small-molecule compound screen identified cannabinoid receptor 1(CB1R)as an upstream regulator of the NLRP3 inflammasome.Mechanistically,antipsychotics competitively bond to the CB1R and led to CB1R translocation to the cytoplasm,where CB1R directly interacted with NLRP3 inflammasome via amino acid residues 177–209,rendering stabilization of the inflammasome.Knockout of Cb1r significantly alleviated antipsychotic-induced cardiomyocyte pyroptosis and cardiotoxicity.Multi-organ-based investigation revealed no additional toxicity of newer CB1R antagonists.In authentic human cases,the expression of CB1R and NLRP3 inflammasome positively correlated with antipsychotics-induced cardiotoxicity.These results suggest that CB1R is a potent regulator of the NLRP3 inflammsome-mediated pyroptosis and smallmolecule inhibitors targeting the CB1R/NLRP3 signaling represent attractive approaches to rescue cardiac side effects of antipsychotics. | Liliang Li Pan Gao Xinru Tang Zheng Liu Mengying Cao Ruoyu Luo Xiaoqing Li Jing Wang Xinyi Lin Chao Peng Zhihong Li Jianhua Zhang Xian Zhang Zhonglian Cao Yunzeng Zou Li Jin | 2022 | Signal Transduction and Targeted Therapy2022，7，7： | 1 |
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