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Calpain-2 activity promotes aberrant endoplasmic reticulum stress-related apoptosis in hepatocytes

World Journal of Gastroenterology 2020年第13期26卷 1450-1462页

作者： Ru-Jia Xie Xiao-Xia Hu Lu Zheng Shuang Cai Yu-Si Chen Yi Yang Ting Yang Bing Han Qin Yang guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases College of Basic Medical SciencesGuizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina Department of Pathophysiology College of Basic Medical SciencesGuizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina Department of Physiology College of Basic Medical SciencesGuizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina

BACKGROUND Calpain-2 is a Ca^2+-dependent cysteine protease,and high calpain-2 activity can enhance apoptosis mediated by multiple triggers.AIM To investigate whether calpain-2 can modulate aberrant endoplasmic reticulum(ER)stress-related apoptosis in rat hepatocyte BRL-3A cells.METHODS BRL-3A cells were treated with varying doses of dithiothreitol(DTT),and their viability and apoptosis were quantified by 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-H-tetrazolium bromide and flow cytometry.The expression of ER stress-and apoptosis-related proteins was detected by Western blot analysis.The protease activity of calpain-2 was determined using a fluorescent substrate,Nsuccinyl-Leu-Leu-Val-Tyr-AMC.Intracellular Ca^2+content,and ER and calpain-2 co-localization were characterized by fluorescent microscopy.The impact of calpain-2 silencing by specific small interfering RNA on caspase-12 activation and apoptosis of BRL-3A cells was quantified.RESULTS DTT exhibited dose-dependent cytotoxicity against BRL-3A cells and treatment with 2 mmol/L DTT triggered BRL-3A cell apoptosis.DTT treatment significantly upregulated 78 kDa glucose-regulated protein,activating transcription factor 4,C/EBP-homologous protein expression by>2-fold,and enhanced PRKR-like ER kinase phosphorylation,caspase-12 and caspase-3 cleavage in BRL-3A cells in a trend of time-dependence.DTT treatment also significantly increased intracellular Ca^2+content,calpain-2 expression,and activity by>2-fold in BRL-3A cells.Furthermore,immunofluorescence revealed that DTT treatment promoted the ER accumulation of calpain-2.Moreover,calpain-2 silencing to decrease calpain-2 expression by 85%significantly mitigated DTT-enhanced calpain-2 expression,caspase-12 cleavage,and apoptosis in BRL-3A cells.CONCLUSION The data indicated that Ca^2+-dependent calpain-2 activity promoted the aberrant ER stress-related apoptosis of rat hepatocytes by activating caspase-12 in the ER.

关键词： Calcium Calpain-2 Caspase-12 Endoplasmic reticulum stress Apoptosis Hepatocyte

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Development and validation of an immunogenic cell death-related prognostic model, and landscape of the tumor immune microenvironment in glioblastoma

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Genes & Diseases 2024年第3期11卷 72-74页

作者： Sha Yang Mei Deng Yunbiao Xiong Bing Xiong Junwu Fu Jia Wang Jiqin Zhang Guoqiang Han Jian Liu Ying Tan guizhou university medical college GuiyangGuizhou 550025China Department of Neurosurgery Guizhou Provincial People's HospitalGuiyangGuizhou 550002China Department of Anesthesiology Guizhou Provincial People's HospitalGuiyangGuizhou 550002China Department of Neurosurgery Chongqing Emergency Medical CenterChongqing400000China

The important role of immunogenic cell death(ICD)in many tumors is increasingly being discovered.However,its mechanisms and potential as a biomarker and therapeutic target in glioblastoma(GBM)have not been well studied.We obtained GBM samples from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases,as well as the immunotherapy cohort from the IMvigor210 study.We used unsupervised clustering to obtain two ICDrelated clusters,corresponding to the ICD-low and ICD-high subtypes respectively,and the tumor immune microenvironment and prognosis of the two subtypes were significantly different.

关键词： immune Cancer prognosis

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Thermosensitive injectable hydrogel loaded with hypoxia-induced exosomes maintains chondrocyte phenotype through NDRG3-mediated hypoxic response

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中国化学快报:英文版 2023年第8期34卷 227-231页

作者： Xiongbo Song Liling Gu Qiming Yang Jiarui Wu Junrong Chen Xiaobin Tian Li Sun Long Chen medical college Guizhou UniversityGuiyang 550000China Department of Orthopedics Guizhou Provincial People’s HospitalGuiyang 550000China Department of Orthopaedics The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550000China

Current clinical treatments cannot effectively delay the progression of osteoarthritis(OA).Consequently,joint replacement surgery is required for late-stage OA when patients cannot tolerate pain and joint dysfunction.Therefore,the prevention of OA progression in the early and middle stages is an urgent clinical problem.In a previous study,we demonstrated that NDRG3-mediated hypoxic response might be closely related to the development and progression of OA.In this study,an injectable thermosensitive hydrogel was established by cross-linking Pluronic F-127 and hyaluronic acid(HA)for the sustained release of hypoxia-induced exosomes(HExos)derived from adipose-derived mesenchymal stem cells.We demonstrated that for OA at the early and middle stages,the HExos-loaded HP hydrogel could maintain the chondrocyte phenotype by enhancing chondrocyte autophagy,reducing chondrocyte apoptosis,and promoting chondrocyte activity and proliferation through the NDRG3-mediated hypoxic response.This novel composite hydrogel,which could activate the NDRG3-mediated hypoxic response,may provide new ideas and a theoretical basis for the treatment of early-and mid-stage OA.

关键词： Osteoarthritis Injectable thermosensitive hydrogel Exosomes Hypoxic response NDRG3

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Efficacy of meridian massage for motor function after a stroke: a systematic review and Meta-analysis

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Journal of Traditional Chinese Medicine 2022年第3期42卷 321-331页

作者： XIE Yunhui GU Hao ZHAO Qing LI Dejie GONG Ying XIE Junxing SHI Guofeng Nursing school Guizhou University of Traditional Chinese MedicineGuiyang 550000China Graduate School Guizhou Medical UniversityGuiyang 550000China guizhou Provincial People’s Hospital Guiyang 550000China Qiannan medical college for Nationalities Duyun 558000China Nanjing medical university Nanjing 210029China Nursing School Guizhou University of Traditional Chinese MedicineGuiyang 550000China

OBJECTIVE:To evaluate the efficacy of meridian massage on motor function after a stroke.METHODS:This systematic review and Meta-analysis of randomised(RCTs)and quasi-randomised controlled trials(q RCTs)was performed to determine the effects of meridian massage on motor dysfunction following a stroke.Articles published until December 2020 related to stroke and meridian massage from National Library of Medicine,Cochrane Central Register of Controlled Trials,Embase,Korea Med,Japan science and Technology Agency,China National Knowledge Infrastructure Database,Wanfang Database,Chinese Biomedical Literature Database and China Science and Technology Journal Database were searched.The primary outcomes included Fugl-Mayer Assessment(FMA),modified Barthel Index(m BI)and clinical efficiency,while the secondary outcomes included modified Ashworth(m AS)and Berg Balance Scale(BBS).Two authors independently selected the literature,extracted the data and assessed the risk of bias,after which Meta-analysis with subgroups and sensitivity analysis was conducted.RESULTS:A total of 16 RCTs and 3 q-RCTs involved 1556 patients satisfied the inclusion.Meta-analysis showed that compared to conventional rehabilitation,meridian massage had significantly better FMA[mean difference(MD)=1.16,95%confidence interval(CI):0.43,1.89,P=0.002],FMA-L(MD=3.21,95%CI:1.97,4.45,P=0.00001),m BI(MD=8.87,95%CI:4.24,13.49,P=0.00002),clinical efficiency[relative risk(RR)=1.37,95%CI:1.24,1.51,P8 weeks(MD=0.89,95%CI:-0.64,2.42,P=0.25)but improving motor function in the meridian massage when the intervention duration was≤8 weeks(<4 weeks intervention duration MD=0.84,95%CI:0.59,1.10,P<0.00001;4–8 weeks MD=2.41,95%CI:0.80,4.01,P=0.003).CONCLUSIONS:Meridian massage as an alternative and complementary therapy seems to have short-term benefits in

关键词： stroke meridian massage motor function Meta-analysis randomized controlled trial

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Metabolic enzyme gene polymorphisms predict the effects of antioxidant treatment on idiopathic male infertility

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Asian Journal of Andrology 2022年第4期24卷 430-435页

作者： Hong-Yan Zhang Yi Mu Pan Chen Dong-Dong Liu Ke-Hang Chen Qi Yu Jun He Fa Sun Jun-Ping Xing Kai-Fa Tang Department of Respiratory Medicine The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Department of Urology The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004China Department of Urology The Sixth's Hospital of Guiyang of Guizhou ProvinceGuiyang 550005China Department of Urology People's Hospital of Guizhou ProvinceGuiyang 550002China Department of Urology The First Affiliated Hospital of Medical College of Xi'an Jiaotong UniversityXi'an 710061China Institute of medical Science of guizhou medical university Guiyang 550004China

To explore the relationship between genetic polymorphisms of metabolic enzymes such as CYP1A1,CYP2D6,GSTM1,GSTT1,and GSTP1 and idiopathic male infertility.By observing the efficacy of antioxidants in the treatment of idiopathic male infertility,the effect of metabolic enzyme gene polymorphisms on antioxidant therapy in patients with idiopathic male infertility was prospectively studied.This case-control study included 310 men with idiopathic infertility and 170 healthy controls.The cytochrome P4501A1(CYP1A1),cytochrome P4502D6(CYP2D6),glutathione S-transferase M1(GSTM1),glutathione S-transferase T1(GSTT1),and glutathione S-transferase P1(GSTP1)genotypes in peripheral blood samples were analyzed by polymerase chain reaction(PCR)and PCR-restriction fragment length polymorphism(PCR-RFLP).The idiopathic male infertility group was treated with vitamin C,vitamin E,and coenzyme Q10 for 3 months and followed up for 6 months.GSTM1(-),GSTT1(-),and GSTM1/T1(-/-)in the idiopathic male infertility groups were more common than those in the control group.The sperm concentration,motility,viability,mitochondrial membrane potential(MMP),and seminal plasma total antioxidant capacity(T-AOC)level in patients with GSTM1(-),GSTT1(-),and GSTM1/T1(-/-)were lower than those in wild-type carriers,and the sperm DNA fragmentation index(DFI),8-hydroxy-2'-deoxyguanosine(8-OH-dG),and malondialdehyde(MDA)and nitric oxide(NO)levels were higher.Therefore,oxidative damage may play an important role in the occurrence and development of idiopathic male infertility,but antioxidant therapy is not effective in male infertility patients with GSTM1 and GSTT1 gene deletions.

关键词： gene infertility metabolic enzyme oxidative stress polymorphisms

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Vulnerable brain regions in adolescent major depressive disorder:A resting-state functional magnetic resonance imaging activation likelihood estimation meta-analysis

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World Journal of Psychiatry 2024年第3期14卷 456-466页

作者： Hui Ding Qin Zhang Yan-Ping Shu Bin Tian Ji Peng Yong-Zhe Hou Gang Wu Li-Yun Lin Jia-Lin Li Department of Radiology The Second People’s Hospital of Guizhou ProvinceGuiyang 550000Guizhou ProvinceChina Department of Radiology Guizhou Provincial People’s HospitalGuiyang 550000Guizhou ProvinceChina Department of Psychiatry of Women and Children The Second People's Hospital of Guizhou ProvinceGuiyang 550000Guizhou ProvinceChina Department of Radiology Zhijin County People's HospitalBijie 552100Guizhou ProvinceChina medical Humanities college Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina

BACKGROUND Adolescent major depressive disorder(MDD)is a significant mental health concern that often leads to recurrent depression in adulthood.Resting-state functional magnetic resonance imaging(rs-fMRI)offers unique insights into the neural mechanisms underlying this condition.However,despite previous research,the specific vulnerable brain regions affected in adolescent MDD patients have not been fully elucidated.AIM To identify consistent vulnerable brain regions in adolescent MDD patients using rs-fMRI and activation likelihood estimation(ALE)meta-analysis.METHODS We performed a comprehensive literature search through July 12,2023,for studies investigating brain functional changes in adolescent MDD patients.We utilized regional homogeneity(ReHo),amplitude of low-frequency fluctuations(ALFF)and fractional ALFF(fALFF)analyses.We compared the regions of aberrant spontaneous neural activity in adolescents with MDD vs healthy controls(HCs)using ALE.RESULTS Ten studies(369 adolescent MDD patients and 313 HCs)were included.Combining the ReHo and ALFF/fALFF data,the results revealed that the activity in the right cuneus and left precuneus was lower in the adolescent MDD patients than in the HCs(voxel size:648 mm3,P<0.05),and no brain region exhibited increased activity.Based on the ALFF data,we found decreased activity in the right cuneus and left precuneus in adolescent MDD patients(voxel size:736 mm3,P<0.05),with no regions exhibiting increased activity.CONCLUSION Through ALE meta-analysis,we consistently identified the right cuneus and left precuneus as vulnerable brain regions in adolescent MDD patients,increasing our understanding of the neuropathology of affected adolescents.

关键词： Major depressive disorder Resting-state functional magnetic resonance imaging Adolescent Activation likelihood estimation Meta-analysis

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APFD:an effective approach to taxi route recommendation with mobile trajectory big data

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Frontiers of Information Technology & Electronic Engineering 2022年第10期23卷 1494-1510页

作者： Wenyong ZHANG Dawen XIA Guoyan CHANG Yang HU Yujia HUO Fujian FENG Yantao LI Huaqing LI college of Data Science and Information Engineering Guizhou Minzu UniversityGuiyang 550025China Department of Automotive Engineering Guizhou Traffic Technician and Transportation CollegeGuiyang 550008China college of Computer Science Chongqing UniversityChongqing 400044China college of Electronic and Information Engineering Southwest UniversityChongqing 400715China The Affiliated Hospital of guizhou medical university Guiyang 550001China

With the rapid development of data-driven intelligent transportation systems,an efficient route recommendation method for taxis has become a hot topic in smart cities.We present an effective taxi route recommendation approach(called APFD)based on the artificial potential field(APF)method and Dijkstra method with mobile trajectory big data.Specifically,to improve the efficiency of route recommendation,we propose a region extraction method that searches for a region including the optimal route through the origin and destination coordinates.Then,based on the APF method,we put forward an effective approach for removing redundant nodes.Finally,we employ the Dijkstra method to determine the optimal route recommendation.In particular,the APFD approach is applied to a simulation map and the real-world road network on the Fourth Ring Road in Beijing.On the map,we randomly select 20 pairs of origin and destination coordinates and use APFD with the ant colony(AC)algorithm,greedy algorithm(A*),APF,rapid-exploration random tree(RRT),non-dominated sorting genetic algorithm-II(NSGA-II),particle swarm optimization(PSO),and Dijkstra for the shortest route recommendation.Compared with AC,A*,APF,RRT,NSGA-II,and PSO,concerning shortest route planning,APFD improves route planning capability by 1.45%–39.56%,4.64%–54.75%,8.59%–37.25%,5.06%–45.34%,0.94%–20.40%,and 2.43%–38.31%,respectively.Compared with Dijkstra,the performance of APFD is improved by 1.03–27.75 times in terms of the execution efficiency.In addition,in the real-world road network,on the Fourth Ring Road in Beijing,the ability of APFD to recommend the shortest route is better than those of AC,A*,APF,RRT,NSGA-II,and PSO,and the execution efficiency of APFD is higher than that of the Dijkstra method.

关键词： Big data analytics Region extraction Artificial potential field Dijkstra Route recommendation GPS trajectories of taxis

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Notoginsenoside R1 attenuates breast cancer progression by targeting CCND2 and YBX3

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Chinese medical Journal 2021年第5期134卷 546-554页

作者： Hai-Long Qin Xue-Jun Wang Bi-Xian Yang Bin Du Xue-Lin Yun college of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyangGuizhou 550000China college of Food and Pharmacy Engineering Guiyang UniversityGuiyangGuizhou 550000China

Background:Breast cancer(BC)is a common malignancy with highly female incidence.So far the function of notoginsenoside R1(NGR1),the extract from Panax notoginseng,has not been clearly elucidated in BC.Methods:Optimal culture concentration and time of NGR1 were investigated by cell counting kit-8 assay.Cell proliferation ability was measured by colony formation assays.Transwell assay was used to detect the effect of NGR1 on cell migration and invasion.The apoptosis rate of cells between each group was measured by TUNEL assay.Results:NGR1 treatment has an inhibitory efect on proliferation,migration,invasion,and angiogenesis and a stimulating effect on cell cycle arrest and apoptosis of Michigan Cancer Foundation-7(MCF-7)cells.The 50%growth inhibitory concentration for MCF-7 cells at 24 h was 148.9 mmol/L.The proportions of MCF-7 cells arrested in the G0/G1 phase were 36.94+6.78%,45.06士5.60%,and 59.46+5.60%in the control group,75,and 150 mmol/L groups,respectively.Furthermore,we revealed that NGR1 treatment attenuates BC progression by targeted downregulating CCND2 and YBX3 genes.Additionally,YBX3 activates phosphatidylinositol 3-phosphate kinase(PI3K)/protein kinase B(Akt)signaling pathway by activating kirsten rat sarcoma viral oncogene,which is an activator of the PI3K/Akt signaling pathway.Conclusion:These results suggest that NGR1 can act as an efficacious drug candidate that targets the YBX3/PI3K/Akt axis in patients with BC.

关键词： Breast cancer Notoginsenoside Rl CCND2 YBX3

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Next-generation sequencing technology for the diagnosis of Pneumocystis pneumonia in an immunocompetent female:A case report

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World Journal of Clinical Cases 2023年第18期11卷 4425-4432页

作者： Jing-Ji Huang Song-Song Zhang Man-Li Liu En-Yu Yang Yu Pan Jing Wu The Second Clinical medical college Guizhou University of Traditional Chinese MedicineGuiyang 550000Guizhou ProvinceChina Intensive Care Unit Guizhou Provincial People's HospitalGuiyang 550000Guizhou ProvinceChina

BACKGROUND Pneumocystis pneumonia(PCP)is a serious fungal infection usually seen in patients with human immunodeficiency virus,and it is more frequently found and has a high fatality rate in immunocompromised people.Surprisingly,it rarely occurs in immunocompetent patients.However,the clinical diagnosis of this pathogen is made more difficult by the difficulty of obtaining accurate microbiological evidence with routine tests.This case reports a PCP patient with normal immune function who was diagnosed through next-generation sequencing(NGS).CASE SUMMARY A 23-year-old female who had no special disease in the past was admitted to the hospital with a persistent fever and cough.Based on the initial examination results,the patient was diagnosed with bipulmonary pneumonia,and empirical broad-spectrum antibiotic therapy was administered.However,due to the undetermined etiology,the patient's condition continued to worsen.She was transferred to the intensive care unit because of acute respiratory failure.After the diagnosis of Pneumocystis jirovecii infection through NGS in bronchoalveolar lavage fluid and treatment with trimethoprim/sulfamethoxazole and caspofungin,the patient gradually recovered and had a good prognosis.CONCLUSION This case emphasizes that,for patients with normal immune function the possibility of PCP infection,although rare,cannot be ignored.NGS plays an important role in the diagnosis of refractory interstitial pneumonia and acute respiratory failure.

关键词： Pneumocystis pneumonia Pneumocystis jirovecii Next-generation sequencing Immunocompetent Trimethoprim/Sulfamethoxazole Case report

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Roles of SET7/9 and LSD1 in the Pathogenesis of Arsenicinduced Hepatocyte Apoptosis

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 364-372页

作者： Bing Han Yi Yang Lei Tang Qin Yang Rujia Xie Department of Pathophysiology College of Basic Medical SciencesGuizhou Medical UniversityGuiyangGuizhouChina guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases Guizhou Medical UniversityGuiyangGuizhouChina Medical College of Guizhou University GuiyangGuizhouChina

Background and Aims:Multiple regulatory mechanisms play an important role in arsenic-induced liver injury.To investigate whether histone H3 lysine 4(H3K4)methyltransferase(SET7/9)and histone H3K4 demethyltransferase(LSD1/KDM1A)can regulate endoplasmic reticulum stress(ERS)-related apoptosis by modulating the changes of H3K4 methylations in liver cells treated with arsenic.Methods:Apoptosis,proliferation and cell cycles were quantified by flow cytometry and real-time cell analyzer.The expression of ERS-and epigenetic-related proteins was detected by Western blot analysis.The antisense SET7/9 expression vector and the overexpressed LSD1 plasmid were used for transient transfection of LO_(2) cells.The effects of NaAsO_(2) on the methylation of H3 in the promoter regions of 78 kDa glucose-regulated protein,activating transcription factor 4 and C/EBP-homologous protein were evaluated by chromatin immunoprecipitation assay.Results:The protein expression of LSD1(1.25±0.08 vs.1.77±0.08,p=0.02)was markedly decreased by treatment with 100μM NaAsO_(2),whereas the SET7/9(0.68±0.05 vs.1.10±0.13,p=0.002)expression level was notably increased,which resulted in increased H3K4me1/2(0.93±0.64,1.19±0.22 vs.0.71±0.13,0.84±0.13,p=0.03 and p=0.003).After silencing SET7/9 and overexpressing LSD1 by transfection,apoptosis rate(in percentage:3.26±0.34 vs.7.04±0.42,4.80±0.32 vs.7.52±0.38,p=0.004 and p=0.02)was significantly decreased and proliferation rate was notably increased,which is reversed after inhibiting LSD1(in percentage:9.31±0.40 vs.7.52±0.38,p=0.03).Furthermore,the methylation levels of H3 in the promoter regions of GRP78(20.80±2.40 vs.11.75±2.47,20.46±2.23 vs.14.37±0.91,p=0.03 and p=0.01)and CHOP(48.67±4.04 vs.16.67±7.02,59.33±4.51 vs.20.67±3.06,p=0.004 and p=0.001)were significantly increased in LO_(2) cells exposed to 100μM NaAsO_(2) for 24 h.Conclusions:Histone methyltransferase SET7/9 and histone demethyltransferase LSD1 jointly regulate the changes of H3K4me1/me2 levels in arsenic-induced apoptosis.NaAsO_(2) induces apop

关键词： Arsenic SET7/9 LSD1 H3K4me1/2 ER stress

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