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Knockdown of HE4 suppresses tumor growth and invasiveness in lung adenocarcinoma through regulation of EGFR signaling

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Oncology Research 2024年第6期32卷 1119-1128页

作者： YUE ZHANG WENYU YANG XIAOWANG HAN YUE QIAO HAITAO WANG TING CHEN tianying LI WEN-BIN OU Department of Biopharmaceutics College of Life Sciences and MedicineZhejiang Provincial Key Laboratory of Silkworm Bioreactor and BiomedicineZhejiang Sci-Tech UniversityHangzhou310018China Department of Thoracic Surgery Zhejiang Provincial People’s HospitalHangzhou310014China

It has been shown that the high expression of human epididymis protein 4(HE4)in most lung cancers is related to the poor prognosis of patients,but the mechanism of pathological transformation of HE4 in lung cancer is still unclear.The current study is expected to clarify the function and mechanism of HE4 in the occurrence and metastasis of lung adenocarcinoma(LUAD).Immunoblotting evaluated HE4 expression in lung cancer cell lines and biopsies,and through analysis of The Cancer Genome Atlas(TCGA)dataset.Frequent HE4 overexpression was demonstrated in LUAD,but not in lung squamous cell carcinoma(LUSC),indicating that HE4 can serve as a biomarker to distinguish between LUAD and LUSC.HE4 knockdown significantly inhibited cell growth,colony formation,wound healing,and invasion,and blocked the G1-phase of the cell cycle in LUAD cell lines through inactivation of the EGFR signaling downstream including PI3K/AKT/mTOR and RAF/MAPK pathways.The first-line EGFR inhibitor gefitinib and HE4 shRNA had no synergistic inhibitory effect on the growth of lung adenocarcinoma cells,while the third-line EGFR inhibitor osimertinib showed additive anti-proliferative effects.Moreover,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in LUAD.Our findings suggest that HE4 positively modulates the EGFR signaling pathway to promote growth and invasiveness in LUAD and highlight that targeting HE4 could be a novel strategy for LUAD treatment.

关键词： Lung adenocarcinoma Human epididymis protein 4 Epidermal growth factor receptor Biomarker Targeted therapies

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Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1380-1399页

作者： Yixian Li Peng Yang Ran Meng Shuting Xu Lingling Zhou Kang Qian Pengzhen Wang Yunlong Cheng Dongyu Sheng Minjun Xu tianying Wang Jing Wu Jinxu Cao Qizhi Zhang Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China

Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.

关键词： Autophagy-lysosome pathway Alzheimer’s disease Proteostasis Neuroinflammation Multi-target therapy Rapamycin Gypenoside XVII Cascade dual-targeting

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自动化行政裁量中算法风险感知的特征与演化研究——基于网络舆情的大数据分析

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公共行政评论 2024年第1期17卷 45-65,M0004页

作者：梁昕刘天颖上海交通大学国际与公共事务学院

随着自动化行政裁量的应用越来越广泛和多元,算法权力扩张、异化、寻租等风险愈发显著,对政府的算法治理造成了挑战。论文运用大数据分析方法,对河南部分村镇银行储户被赋红码事件的全国9328条相关微博文本进行挖掘,发现公众对算法风险... 详细信息

随着自动化行政裁量的应用越来越广泛和多元,算法权力扩张、异化、寻租等风险愈发显著,对政府的算法治理造成了挑战。论文运用大数据分析方法,对河南部分村镇银行储户被赋红码事件的全国9328条相关微博文本进行挖掘,发现公众对算法风险具有高度的敏感性,舆情的爆发性较强且情感值较为负面,其中意见领袖是负面情感的主要引领者;公众关注度呈现高度的空间聚集性,经济发达地区的关注度聚集性更强;两次赋红码事件的公众情绪有显著的差异,且随着事件的演化,不同主体关注的焦点也呈现出高度的异质性。基于分析结果,政府在自动化行政裁量中的算法治理依然面临较大挑战,需要重点关注的方向包括:明晰行政裁量中算法权力的边界;减少自动化行政裁量中因委托-代理关系引发的道德风险问题;提升算法风险沟通的及时性和有效性,避免公众消极态度的产生。

关键词：算法行政裁量风险大数据

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Room temperature liquid metal:its melting point,dominating mechanism and applications

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Frontiers in Energy 2020年第1期14卷 81-104页

作者： Junheng FU Chenglin ZHANG tianying liu Jing liu CAS Key Laboratory of Cryogenics Technical Institute of Physics and ChemistryChinese Academy of Sciences Beijing 100190China School of Future Technology University of Chinese Academy of Sciences Beijing 100049China Beijing Key Laboratory of Cryo-Biomedical Engineering Beijing 100190China CAS Key Laboratory of Cryogenics Technical Institute of Physics and ChemistryChinese Academy of SciencesBeijing 100190China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China Department of Biomedical Engineering School of MedicineTsinghua UniversityBeijing 100084China

The room temperature liquid metal(LM)is recently emerging as a new class of versatile materials with fascinating characteristics mostly originated from its simultaneous metallic and liquid natures.The melting point is a typical parameter to describe the peculiarity of LM,and a pivotal factor to consider concerning its practical applications such as phase change materials(PCMs)and advanced thermal management.Therefore,the theoretical exploration into the melting point of LM is an essential issue,which can be of special value for the design of new LM materials with desired properties.So far,some available strategies such as molecular dynamics(MD)simulation and classical thermodynamic theory have been applied to perform correlative analysis.This paper is primarily dedicated to performing a comprehensive overview regarding typical theoretical strategies on analyzing the melting points.It,then,presents evaluations on several factors like components,pressure,size and supercooling that may be critical for melting processes of liquid metal.After that,it discusses applications associated with the characteristic of low melting points of LM.It is expected that a great many fundamental and practical works are to be conducted in the coming future.

关键词： melting point liquid metal crystal thermodynamics molecular dynamics

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Effectiveness and safety of acupuncture in treatment of pregnancyrelated symptoms:a systematic review and Meta-analysis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 16-26页

作者： liu Tingting liu Tongou liu Mingfu School of Traditional Chinese Medicine Clinical Medicine Hubei University of Traditional Chinese MedicineWuhan 430000China First Clinical College of Hubei University of Traditional Chinese Medicine Wuhan 430000China Department of Acupuncture and Tuina Affiliated Hospital of Hubei University of Traditional Chinese MedicineHubei Provincial Hospital of Traditional Chinese MedicineWuhan 430000China

OBJECTIVE:To systematically evaluate the efficacy and safety of acupuncture(AM)in the treatment of pregnancyrelated symptoms such as acute vomiting during pregnancy.METHODS:We comprehensively searched the available literature up to November 2021,including Pub Med,Embase,Cochrane Library,Chinese Biomedical Literature Database,and China National Knowledge Infrastructure Database,for randomized controlled trials(RCTs)on AM for the treatment of severe vomiting,insomnia,pharyngeal and pelvic pain,mood abnormalities,and dyspepsia during pregnancy.RESULTS:Sixteen RCTs with a cumulative sample size of 1178 cases were included.Of these,964 patients were included in the Meta-analysis.The Meta-analysis results showed that AM was more efficient than Western medicine in treating discomfort during pregnancy[odds ratio(OR)=1.19,95%confidence interval(CI)(1.11,1.28),P<0.01].AM was better than the control group in improving the visual analog scale scores[standard mean difference(SMD)=0.62,95%CI(0.53,0.71),P<0.01].AM was superior to the control group in improving Numerical Rating Scale(NRS)symptom scores[OR=7.31,95%CI(3.36,15.94),P<0.01].There was no significant difference in adverse effects between the AM and sham-AM groups and the analgesic drug group[OR=0.70,95%CI(0.39,1.28),P=0.25],but the treatment and control groups had mild adverse effects with a low incidence.CONCLUSIONS:AM is more effective than other treatments or pharmacotherapy alone in the treatment of pregnancy-related symptoms,and is relatively safe.However,the quality of the included trials was rather poor,and high-quality studies are required to confirm our findings.

关键词： acupuncture pregnancy nausea vomiting sleep initiation and maintenance disorders low back pain pelvic pain mood abnormalities Meta-analysis systematic review

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Novel de novo TRPV4 mutation identified in a Chinese family with metatropic dysplasia inhibits chondrogenic differentiation

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Genes & Diseases 2024年第3期11卷 83-86页

作者： Ping Wei Weizhe Shi tianying Nong Caixia Xian Xia Li Zhaohui Li Xin Li Jianping Wu Liyuan Shang Fulong Xu Yibo Xu Hongwen Xu Mingwei Zhu Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouGuangdong 510623China Department of Pediatric Orthopedics Guangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangdong Provincial Clinical Research Center for Child HealthGuangzhouGuangdong 510623China

Metatropicdysplasia(MD,MIM156530)is a rare congenital bone dysplasia primarily characterized by severe platyspondyly with long and wide vertebral bodies and dumbbell deformity of the tubular bones.MD can be caused by heterozygous mutations in the gene encoding transient receptor potential vanilloid family member 4(TRPV4).We identifieda novel de novo mutation,c.2353T>C,in the TRPV4 gene,in a Chinese family with mild MD.

关键词： TRPV4 dysplasia congenital

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CEFR蒸汽发生器给水调节系统的设计与调试

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核动力工程 2024年第2期45卷 183-186页

作者：刘勇段天英冯伟伟张玮瑛中国原子能科学研究院北京102413

蒸汽发生器给水调节系统是中国实验快堆(CEFR)重要的控制系统,需要实现自动控制。根据该系统的控制需求针对性地设计了一套给水调节控制方案,并在CEFR实堆功率运行工况下验证了该控制方案。堆上试验结果表明,该控制方案能够在各种设计... 详细信息

蒸汽发生器给水调节系统是中国实验快堆(CEFR)重要的控制系统,需要实现自动控制。根据该系统的控制需求针对性地设计了一套给水调节控制方案,并在CEFR实堆功率运行工况下验证了该控制方案。堆上试验结果表明,该控制方案能够在各种设计工况下维持蒸汽发生器出口钠温稳定,具备抑制反应堆其他参数干扰的能力。本研究通过CEFR蒸汽发生器给水调节系统的设计与调试工作,实现了CEFR蒸汽发生器给水调节系统的自动化控制。

关键词： CEFR 蒸汽发生器给水调节系统自动控制

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Printed flexible thin-film transistors based on different types of modified liquid metal with good mobility

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Science China(Information Sciences) 2019年第10期62卷 182-193页

作者： Qian LI Ju LIN tianying liu Han ZHENG Jing liu Beijing Key Lab of Cryo-Biomedical Engineering and Key Lab of Cryogenics Technical Institute of Physics and ChemistryChinese Academy of Sciences Department of Biomedical Engineering School of MedicineTsinghua University School of Engineering Science University of Chinese Academy of Sciences Beijing DREAM Ink Technologies Co. Ltd.

High-performance logic circuits fabricated on flexible or unconventional substrates have become a necessity for several new applications. Generally, compared to those fabricated on more rigid substrates,printed, large-area, and flexible thin film transistors(TFTs) are prone to under-performance, which severely limits their practical value. The realization of printed flexible macroelectronics requires advancements in material science and novel fabricating techniques. In this study, using a fast printing process, we manufacture liquid metal-carbon nanotube TFTs on a thin polyethylene terephthalate substrate. These flexible TFTs(ptype) exhibit enhance stability and flexibility, carrier mobility(10.61 cm2V-1s-1), and transconductance(0.88 μS). Furthermore, we realize dependable n-type and ambipolar transistors based on liquid metals with charge transport efficiencies that are comparable to our p-type counterparts, thus providing a foundation for manufacturing integrated circuits and complementary logic gates on flexible substrates. This study shows the positive progress of liquid metal printing-enabled functional devices and discusses the possibility of practical applications; moreover, it sets the foundation for printed high-performance and large-area flexible liquid metal electronics.

关键词： liquid metal carbon nanotube field-effect transistors printed devices carrier mobility

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Removal of Cr(Ⅵ)by glutaraldehyde-crosslinked chitosan encapsulating microscale zero-valent iron:Synthesis,mechanism,and longevity

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Journal of Environmental Sciences 2024年第8期142卷 115-128页

作者： Yijun Duan Fang liu Xiang liu Miao Li School of Environment Tsinghua UniversityBeijing 100084China Transportation Institute of Inner Mongolia University Hohhot 010070China

Microscale zero-valent iron(mZVI)has shown great potential for groundwater Cr(Ⅵ)remediation.However,low Cr(Ⅵ)removal capacity caused by passivation restricted the wide use of mZVI.We prepared mZVI/GCS by encapsulating mZVI in a porous glutaraldehydecrosslinked chitosan matrix,and the formation of the passivation layer was alleviated by reducing the contact between zero-valent iron particles.The average pore diameter of mZVI/GCS was 8.775 nm,which confirmed the mesoporous characteristic of this material.Results of batch experiments demonstrated that mZVI/GCS exhibited high Cr(Ⅵ)removal efficiency in a wide range of pH(2-10)and temperature(5-35℃).Common groundwater coexisting ions slightly affected m ZVI/GCS.The material showed great reusability,and the average Cr(Ⅵ)removal efficiency was 90.41%during eight cycles.In this study,we also conducted kinetics and isotherms analysis.Pseudo-second-order model was the most matched kinetics model.The Cr(Ⅵ)adsorption process was fitted by both Langmuir and Freundlich isotherms models,and the maximum Langmuir adsorption capacity of m ZVI/GCS reached243.63 mg/g,which is higher than the adsorption capacities of materials reported in most of the previous studies.Notably,the column capacity for Cr(Ⅵ)removal of a mZVI/GCS-packed column was 6.4 times higher than that of a mZVI-packed column in a 50-day experiment.Therefore,mZVI/GCS with a porous structure effectively relieved passivation problems of mZVI and showed practical application prospects as groundwater Cr(Ⅵ)remediation material with practical application prospects.

关键词： Chitosan Glutaraldehyde mZVI Cr(Ⅵ) Groundwater

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Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Protein & Cell 2024年第2期15卷 121-134页

作者： Hui Sun Tingting Deng Yali Zhang Yanling Lin Yanan Jiang Yichao Jiang Yang Huang Shuo Song Lingyan Cui Tingting Li Hualong Xiong Miaolin Lan Liqin liu Yu Li Qianjiao Fang Kunyu Yu Wenling Jiang Lizhi Zhou Yuqiong Que tianying Zhang Quan Yuan Tong Cheng Zheng Zhang Hai Yu Jun Zhang Wenxin Luo Shaowei Li Qingbing Zheng Ying Gu Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China State Key Laboratory of Vaccines for Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China Xiang An Biomedicine Laboratory Xiamen 361102China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSchool of MedicineSouthem University of Science and TechnologyShenzhen 518112China The Second Affliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or vaccination.The rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus strain.Here,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron subvariants.Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing.Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5.Together,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

关键词： SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

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