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Indirubin suppresses 4T1 murine breast cancer in vitro and in vivo by induction of ferroptosis

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TMR Modern Herbal Medicine 2022年第1期5卷 1-9页

作者： Xiu-Ping Kuang Ji-Wei Huang Ying-Nan Jiang Yong-Zhi Guo chang-yu yan Wei-Xi Li yunnan University of Traditional Chinese Medicine Kunming 650500YunnanChina Perfect Life Sciences Research Institute Zhongshan 528400GuangdongChina Department of Pharmacy The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510630GuangdongChina School of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Objective Indirubin,isolated from Indigo Naturals,has been reported to have the inhibitory activity of MCF-7 human breast cancer cells in vitro.However,studies on its anti-breast cancer activity in vivo and the underlying mechanism are insufficient.We explored whether indirubin could trigger ferroptosis of breast cancer cells to exert anti-tumor activity.Methods Bioinformatical analysis was performed to detect the expression of prostaglandin-endoperoxide synthase 2(Ptgs2)in breast cancer tissues and Ptgs2-related prognosis for patients with breast cancer.The inhibitory effects of indirubin on 4T1 cells were assessed using MTT assay and LDH activity detection.The levels of 4-HNE,GPX4,PTGS2 and GSK-3βproteins were detected by Western blotting,and the mRNA of Ptgs2 was tested by qPCR.The contents of GSH and MDA were determined by commercial kits.Molecular docking was employed to study the interaction between indirubin and GSK-3β.A 4T1 murine breast cancer was adopted to evaluate the in vivo antitumor activity of indirubin.Results Indirubin promoted ferroptosis of 4T1 breast cancer cells with depleting of GSH,increased MDA and 4-HNE levels,as well as decreased GPX4 expression.Indirubin suppressed 4T1 breast tumor in vivo.The mechanism study showed indirubin up-regulated Ptgs2 expression by promoting phosphorylation(Ser 9)of GSK-3β.Conclusion Indirubin suppresses 4T1 murine breast cancer in vitro and in vivo by induction of ferroptosis.

关键词： Breast cancer Indirubin Ferroptosis Ptgs2 GSK-3β

Inhibitory effects of baicalein against herpes simplex virus type 1

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Acta Pharmaceutica Sinica B 2020年第12期10卷 2323-2338页

作者： Zhuo Luo Xiu-Ping Kuang Qing-Qing Zhou chang-yu yan Wen Li Hai-Biao Gong Hiroshi Kurihara Wei-Xi Li Yi-Fang Li Rong-Rong He Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility College of PharmacyCollege of PharmacyJinan UniversityGuangzhou 612505China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhou 612505China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou 612505China yunnan University of Traditional Chinese Medicine Kunming 650550China

Herpes simplex virus type 1(HSV-1)is a ubiquitous and widespread human pathogen,which gives rise to a range of diseases,including cold sores,corneal blindness,and encephalitis.Currently,the use of nucleoside analogs,such as acyclovir and penciclovir,in treating HSV-1 infection often presents limitation due to their side effects and low efficacy for drug-resistance strains.Therefore,new anti-herpetic drugs and strategies should be urgently developed.Here,we reported that baicalein,a naturally derived compound widely used in Asian countries,strongly inhibited HSV-1 replication in several models.Baicalein was effective against the replication of both HSV-1/F and HSV-1/Blue(an acyclovir-resistant strain)in vitro.In the ocular inoculation mice model,baicalein markedly reduced in vivo HSV-1/F replication,receded inflammatory storm and attenuated histological changes in the cornea.Consistently,baicalein was found to reduce the mortality of mice,viral loads both in nose and trigeminal ganglia in HSV-1 intranasal infection model.Moreover,an ex vivo HSV-1-EGFP infection model established in isolated murine epidermal sheets confirmed that baicalein suppressed HSV-1 replication.Further investigations unraveled that dual mechanisms,inactivating viral particles and inhibiting IκB kinase beta(IKK-β)phosphorylation,were involved in the anti-HSV-1 effect of baicalein.Collectively,our findings identified baicalein as a promising therapy candidate against the infection of HSV-1,especially acyclovir-resistant strain.

关键词： Anti-HSV-1 Baicalein Viral inactivation IKK-βphosphorylation NF-kβactivation HSV-1 infection

中学女教师心理健康状况及影响因素Logistic回归方程构建

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中国健康教育 2024年第1期40卷 8-14,26页

作者：李雪霏徐茗王姿欢俞文兰于常艳中国疾病预防控制中心职业卫生与中毒控制所北京100050 北京市疾病预防控制中心北京100013

目的分析中学女教师心理健康状况并构建影响因素Logistic回归方程。方法于2020年6—10月采取分层随机整群抽样方法抽取12所中学的1899名中学女教师纳入研究,采用电子问卷的方式进行调查,筛选中学女教师焦虑、抑郁的影响因素,建立Logisti... 详细信息

目的分析中学女教师心理健康状况并构建影响因素Logistic回归方程。方法于2020年6—10月采取分层随机整群抽样方法抽取12所中学的1899名中学女教师纳入研究,采用电子问卷的方式进行调查,筛选中学女教师焦虑、抑郁的影响因素,建立Logistic回归方程并验证。结果1754例中学女教师发生焦虑487例,抑郁463例,焦虑率为27.77%、抑郁率为26.40%。多因素Logistic分析结果显示,年龄>45岁、周均工作时间>40 h、合并慢性疾病、职业压力中或重的中学女教师焦虑发生率高于年龄≤45岁、周均工作时间≤40 h、未合并慢性疾病、职业压力轻者,OR值分别为2.248(95%CI:1.625~3.110)、3.838(95%CI:2.828~5.209)、3.860(95%CI:2.831~5.262)、3.004(95%CI:2.132~4.233),积极参与心理健康讲座和团体心理辅导的中学女教师焦虑发生率低于未积极参与者,OR值为0.248(95%CI:0.181~0.339);周均工作时间>40 h、兼任行政职务、合并慢性疾病、职业压力中或重的中学女教师抑郁发生率高于周均工作时间≤40 h、未兼任行政职务、未合并慢性疾病、职业压力轻,OR值分别为3.259(95%CI:2.414~4.398)、2.273(95%CI:1.672~3.089)、2.857(95%CI:2.102~3.883)、3.451(95%CI:2.415~4.931),积极参与心理健康讲座和团体心理辅导的中学女教师抑郁发生率低于未积极参与者,OR值为0.302(95%CI:0.223~0.410);以上P均<0.05。根据训练集构建Logistic回归方程,在验证集预测焦虑、抑郁曲线下面积分别为0.786、0.736。结论中学女教师焦虑、抑郁发生率较高,受多种因素影响,据此建立影响因素Logistic回归方程,预测价值较高,可对高危人员采取相应预防对策。

关键词：中学女教师心理健康影响因素 Logistic回归

基于恒速压汞技术研究安塞油田S区储层孔隙结构特征

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内蒙古石油化工 2024年第4期50卷 79-82页

作者：苏成余常燕曹燕燕刘波长庆油田分公司第一采油厂陕西延安716000

为准确评价安塞油田S区储层孔隙结构特征,利用恒速压汞实验,研究了孔隙和喉道的分布特征以及孔喉半径比特征参数与孔渗间的关系。结果表明:不同渗透率的岩心样品孔隙半径分布范围基本相同,主要分布在120~340μm之间,平均孔隙半径在240μ... 详细信息

为准确评价安塞油田S区储层孔隙结构特征,利用恒速压汞实验,研究了孔隙和喉道的分布特征以及孔喉半径比特征参数与孔渗间的关系。结果表明:不同渗透率的岩心样品孔隙半径分布范围基本相同,主要分布在120~340μm之间,平均孔隙半径在240μm左右;喉道半径主要分布在23μm以内;孔喉半径比与渗透率呈正相关关系,是影响S区储层渗流能力的主要因素。

关键词：安塞油田恒速压汞孔隙结构喉道半径

Novel insights into stress-induced susceptibility to influenza:corticosterone impacts interferon-βresponses by Mfn2-mediated ubiquitin degradation of MAVS

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Signal Transduction and Targeted Therapy 2020年第1期5卷 782-793页

作者： Zhuo Luo Li-Fang Liu Ying-Nan Jiang Lu-Ping Tang Wen Li Shu-Hua Ouyang Long-Fang Tu yan-Ping Wu Hai-Biao Gong chang-yu yan Shan Jiang yu-Hui Lu Tongzheng Liu Zhenyou Jiang Hiroshi Kurihara yang yu Xin-Sheng Yao Yi-Fang Li Rong-Rong He Guangdong Engineering Research Center of Chinese Medicine&Disease Susceptibility Jinan UniversityGuangzhou 510632China International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhou 510632China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China Institute of Tumor Pharmacology College of PharmacyJinan UniversityGuangzhou 510632China Department of Microbiology and Immunology Basic Medicine CollegeJinan UniversityGuangZhou 510632China

Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung inflammation.Corticosterone(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed mice.We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice.Mechanistically,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in vitro.Furthermore,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this process.Gain-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS.Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.

关键词： influenza ubiquitin MAVS

Prediction of Th17/Treg cell balance on length of stay in intensive care units of patients with sepsis

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Journal of Intensive Medicine 2024年第2期4卷 240-246页

作者： yu Wu Guosheng Wu Minyu Li Yongqing chang Miao yu yan Meng Xiaojian Wan Department of Intensive Care Medicine Changhai HospitalNaval Medical UniversityShanghaiChina Department of Anesthesiology Bethune International Peace HospitalShijiazhuangHebeiChina Department of Burns Changhai HospitalNaval Medical UniversityShanghaiChina Department of Special Needs Clinic Changhai HospitalNaval Medical UniversityShanghaiChina

Background Prolonged length of stay(LOS)of sepsis can drain a hospital's material and human resources.This study investigated the correlations between T helper type 17(Th17)and regulatory T(Treg)balance with LOS in sepsis.Methods A prospective clinical observational study was designed in changhai Hospital affiliated to Naval Medical University in Shanghai,China,from January to October 2020.The patients diagnosed with sepsis and who met the inclusion and exclusion criteria were recruited and whether the levels of cytokines,procalcitonin,subtypes,and biomarkers of T cells in the peripheral blood were detected.We analyzed the correlation between these and LOS.Results Sixty septic patients were classified into two groups according to whether their intensive care unit(ICU)stay exceeded 14 days.The patients with LOS≥14 days were older([72.6±7.5]years vs.[63.3±10.4]years,P=0.015)and had higher Sequential Organ Failure Assessment(SOFA)(median[interquartile range]:6.5[5.0–11.0]vs.4.0[3.0–6.0],P=0.001)and higher Acute Physiology and Chronic Health Evaluation(APACHE)II scores(16.0[13.0–21.0]vs.8.5[7.0–14.0],P=0.001).There was no difference in other demographic characteristics and cytokines,interleukin-6,tumor necrosis factor-α,and interleukin-10 between the two groups.The Th17/Treg ratio of sepsis with LOS<14 days was considerably lower(0.48[0.38–0.56]vs.0.69[0.51–0.98],P=0.001).For patients with LOS≥14 days,the area under the receiver operating characteristic curve for the Th17/Treg ratio was 0.766.It improved to 0.840 and 0.850 when combined with the SOFA and APACHE II scores,respectively.Conclusions The Th17/Treg ratio was proportional to septic severity and can be used as a potential predictor of ICU stay in sepsis,presenting a new option for ICU practitioners to better care for patients with sepsis.

关键词： Sepsis Th17/Treg Length of stay Intensive care units

Microscopic nonlinear optical activities and ultrafast carrier dynamics in layered AgInP_(2)S_(6)

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Photonics Research 2024年第4期12卷 691-700页

作者： ZIXIN WANG NINGNING DONG yu MAO CHENDUAN CHEN XIN CHEN chang XU ZHOUyuAN yan JUN WANG Aerospace Laser Technology and Systems Department CAS Key Laboratory of Materials for High-Power LaserShanghai Institute of Optics and Fine MechanicsChinese Academy of SciencesShanghai 201800China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China CAS Center for Excellence in Ultra-intense Laser Science(CEULS) State Key Laboratory of High Field Laser PhysicsShanghai Institute of Optics and Fine MechanicsChinese Academy of SciencesShanghai 201800China

Since the emergence of graphene, transition metal dichalcogenides, and black phosphorus, two-dimensional materials have attracted significant attention and have driven the development of fundamental physics and optoelectronic devices. Metal phosphorus trichalcogenides(MPX3), due to their large bandgap of 1.3–3.5 eV, enable the extension of optoelectronic applications to visible and ultraviolet(UV) wavelengths.

关键词： nonlinear ultraviolet phosphorus

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第13期30卷 1810-1814页

作者： yan-Bo yu Department of Gastroenterology Laboratory of Translational GastroenterologyQilu HospitalShandong UniversityJinan 250012Shandong ProvinceChina

In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

关键词： Superficial esophageal squamous cell carcinoma Endoscopic resection Lymph node metastasis Risk factors Tumor budding Predictive model

SMXL5 attenuates strigolactone signaling in Arabidopsis thaliana by inhibiting SMXL7 degradation

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Molecular Plant 2024年第4期17卷 631-647页

作者： Qingtian Li Haiyang yu Wenwen chang Sunhyun chang Michael Guzman Lionel Faure Eva-Sophie Wallner Heqin yan Thomas Greb Lei Wang Ruifeng Yao David C.Nelson Department of Botany and Plant Sciences University of CaliforniaRiversideRiversideCA 2521USA Yazhouwan National Laboratory Sanya 572025China Hainan Seed Industry Laboratory Sanya 57205China State Key Laboratory of Chemo/Biosensing and Chemometrics Hunan Provincial Key Laboratory of Plant Functional Genomics and Developmental RegulationCollege of BiologyHunan UniversityChangsha 410082China Key Laboratory of Seed Innovation Center for Agricultural Resources ResearchInstitute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuangHebei 050021China University of Chinese Academy of Sciences Beijing 10004China School of the Sciences Biology DivisionTexas Woman’s UniversityDentonTX 76204USA Centre for Organismal Studies(COS) Heidelberg University6120 HeidelbergGermany

Hormone-activated proteolysis is a recurring theme of plant hormone signaling mechanisms.In strigolactone signaling,the enzyme receptor DWARF14(D14)and an F-box protein,MORE AXILLARY GROWTH2(MAX2),mark SUPPRESSOR OF MAX21-LIKE(SMXL)family proteins SMXL6,SMXL7,and SMXL8 for rapid degradation.Removal of these transcriptional corepressors initiates downstream growth responses.The homologous proteins SMXL3,SMXL4,and SMXL5,however,are resistant to MAX2-mediated degradation.We discovered that the smxl4 smxl5 mutant has enhanced responses to strigolactone.SMXL5 attenuates strigolactone signaling by interfering with AtD14-SMXL7 interactions.SMXL5 interacts with AtD14 and SMXL7,providing two possible ways to inhibit SMXL7 degradation.SMXL5 function is partially dependent on an ethylene-responsive-element binding-factor-associated amphiphilic repression(EAR)motif,which typically mediates interactions with the TOPLESS family of transcriptional corepressors.However,we found that loss of the EAR motif reduces SMXL5-SMXL7 interactions and the attenuation of strigolactone signaling by SMXL5.We hypothesize that integration of SMXL5 into heteromeric SMXL complexes reduces the susceptibility of SMXL6/7/8 proteins to strigolactone-activated degradation and that the EAR motif promotes the formation or stability of these complexes.This mechanism may provide a way to spatially or temporally fine-tune strigolactone signaling through the regulation of SMXL5 expression or translation.

关键词： Arabidopsis typically inhibiting