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EMT transcription factors activated circuits:A novel tool to study EMT dynamics and its therapeutic implications

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Synthetic and Systems Biotechnology 2024年第1期9卷 1-10页

作者： tianying Chen Wangyue Jia Bo Zhang Hanqi Xie Qiong Wu MOE Key Laboratory of Bioinformatics Center for Synthetic and System BiologySchool of Life SciencesTsinghua UniversityBeijing100084China

The epithelial mesenchymal transition(EMT)plays significant roles in the progression of cancer and fibrotic ***,this process is reversible,resulting in mesenchymal epithelial transition(MET),which plays an important role in cancer *** is a lack of methods to trace and target EMT cells using synthetic biology circuits,which makes it difficult to study the cell fate or develop targeted *** this study,we introduced responsive EMT sensing circuits,which sense the EMT using specific promoters that respond to transcription factors typical of EMT activation(EMT-TFs).The transcriptional strength of EMT-sensing promoters decreased more than 13-fold in response to the overexpression of the ***,the NOT gate circuits were built by placing the tetR transcription repressor under the control of EMT sensing promoters and expressed an output signal using the constitutive CMV promoter modified with tetO sites This circuit is named EMT sensing and responding *** the EMT transcription factors was present,we observed a 5.8-fold signal increase in the ***,we successfully distinguished mesenchymal breast cancer cells from epithelial cancer cells and repressed the proliferation of EMT tumor cells using our *** EMT sensing and responding circuits are promising tools for the identification of EMT cells,which is crucial for EMT-related disease therapy and investigating the mechanisms underlying the reversible EMT process.

关键词： Epithelial mesenchymal transition Synthetic biology Tumor killing

Resistance to salt stresses by aerobic granular sludge:sludge property and microbial community

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Frontiers of Environmental Science & Engineering 2024年第8期18卷 107-116页

作者： Xiao Wu Hui Li Meili Wang tianying Zhang Jiawei Li Yongdi Liu Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission School of Chemistry and EnvironmentSouthwest Minzu UniversityChengdu 610041China Institute for Environmental Pollution and Health School of Environmental and Chemical EngineeringShanghai UniversityShanghai 200444China School of Life Sciences Southwest UniversityChongqing 400715China State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process School of Resources and Environmental EngineeringEast China University of Science and TechnologyShanghai 200237China Institute of Qinghai-Tibetan Plateau Southwest Minzu UniversityChengdu 610041China

Saline wastewater is regarded as a challenge for wastewater treatment plants because high-salinity conditions negatively affect on traditional biological *** granular sludge(AGS)has gained attention as a promising technology for saline wastewater treatment because of its compact structure and the ability to withstand toxic ***,this study investigated the saltresistance performance,sludge properties and microbial community of AGS under low-salinity and high-salinity conditions,with the saline concentrations ranging from 0 to 50 g/*** results showed that AGS could withstand long-term saline stresses,and the maximum salinity reached 50 g/L within 113 *** salinities of 10,30,and 50 g/L,the chemical oxygen demand(COD)removal efficiencies were 90.3%,88.0%and 78.0%,*** also its maintained strength and aggregation at salinities of 10 and 30 g/*** of extracellular polymeric substances(EPS)by non-halophilic bacteria that enhanced sludge *** compact structure that ensured the microorganisms bioactivity helped to remove organic matters under salinities of 10 and 30 g/*** a salinity of 50 g/L,moderately halophilic bacteria,including Salinicola,Thioclava,Idiomarina and Albirhodobacter,prevailed in the *** dominant microbial communities shifted to moderately halophilic bacteria,which could maintain aerobic granular stabilization and remove organic matters under 50 g/L *** results in this study provide a further explanation for the long-term operation of AGS for treating saline wastewater at different *** is hoped that this work could bring some clues for the mystery of salt-resistance mechanisms.

关键词： Aerobic granular sludge Long-term saline stresses Performance Sludge property Microbial community

Tandem electrocatalysis for CO2 reduction to multi-carbons

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Science China Chemistry 2024年第11期67卷 3631-3651页

作者： Xindi Li Tianxiang Yan Yichen Meng Zhanpeng Liang tianying Zhang Haoyuan Chi Ziting Fan Yifan Jin Haoran Zhang Sheng Zhang Key Laboratory for Green Chemical Technology of Ministry of Education Collaborative Innovation Centre of Chemical Science and Engineering School of Chemical Engineering and Technology Tianjin University Joint School of National University of Singapore and Tianjin University International Campus of Tianjin University Haihe Laboratory of Sustainable Chemical Transformations

The rising CO2concentration in the atmosphere due to extensive use of fossil fuels has led to serious climate and environmental issues. One efficient solution is that CO2capture from industrial emissions followed its conversion into value-added chemicals driven by renewable energies. CO2electroreduction（CO2RR） features a green and sustainable fashion towards effective CO2conversion, but still suffers from low multi-carbon selectivity and yield. Considering the pivotal role of CO intermediate in C–C coupling to multi-carbon formation, tandem CO2RR systems with separated CO generation and consumption components could facilitate the coupling between *CO-based intermediates to energy-intensive multi-carbons by manipulating CO diffusion and surface coverage. In this aspect, we comprehensively reviewed the design principles of tandem systems for CO2electroreduction reaction. The chemistry behind the C–C coupling regarding to their distribution and diffusion was initially introduced, which was followed by achievements on tandem architectures, from catalysts, electrodes to systems. Future directions and perspectives on advanced tandem system designs for CO2RR were discussed at the end. This review contributes to the understanding of structureperformance correlations in tandem catalysis and helps guide the effective collection of multi-carbons of high-yield and highselectivity.

关键词： electrocatalytic CO2 reduction tandem electrocatalysis design CO mass transfer model

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 *** 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)*** 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 ***4 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 *** 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 ***,we provided evidence that HE4 regulated EGFR expression by transcription regulation and protein interaction in *** 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

Robust tube-based MPC with smooth computation for dexterous robot manipulation

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Science China(Information Sciences) 2024年第11期67卷 252-268页

作者： Yu LUO tianying JI Fuchun SUN Qie SIMA Huaping LIU Mingxuan JING Jianwei ZHANG Department of Computer Science and Technology Tsinghua University Science & Technology on Integrated Information System Laboratory Institute of Software Chinese Academy of Sciences Department of Informatics University of Hamburg

Dexterous robot manipulation has shone in complex industrial scenarios, where multiple manipulators, or fingers, cooperate to grasp and manipulate objects. When encountering multi-objective optimization with system constraints in such scenarios, model predictive control(MPC) has demonstrated exceptional performance in complex multi-robot manipulation tasks involving multi-objective optimization with system constraints. However, in such scenarios, the substantial computational load required to solve the optimal control problem(OCP) at each triggering instant can lead to significant delays between state sampling and control application, hindering real-time performance. To address these challenges, this paper introduces a novel robust tube-based smooth MPC approach for two fundamental manipulation tasks: reaching a given target and tracking a reference trajectory. By predicting the successor state as the initial condition for imminent OCP solving, we can solve the forthcoming OCP ahead of time, alleviating delay effects. Additionally,we establish an upper bound for linearizing the original nonlinear system, reducing OCP complexity and enhancing response speed. Grounded in tube-based MPC theory, the recursive feasibility and closed-loop stability amidst constraints and disturbances are ensured. Empirical validation is provided through two numerical simulations and two real-world dexterous robot manipulation tasks, which shows that the seamless control input by our methods can effectively enhance the solving efficiency and control performance when compared to conventional time-triggered MPC strategies.

关键词： dexterous robot manipulation model predictive control smooth computation

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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 *** 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

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 *** 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 ***,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD ***,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside *** by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected *** 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 ***,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic *** 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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论西夏黑水城地区的土地流转——以黑水城出土西夏契约为中心

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敦煌学辑刊 2024年第1期1卷 125-133页

作者：赵天英兰州文理学院“一带一路”文化艺术研究院甘肃兰州730000

黑水城出土的西夏契约表明西夏黑水城地区的土地以买卖、典当、租赁的形式流转。通过流转,土地被寺庙和大地主兼并。寺庙和大地主利用经济上的优势,通过粮食借贷的高息、土地和牲畜租赁的高额租金,迫使农民破产,不得不低价卖掉土地。西... 详细信息

黑水城出土的西夏契约表明西夏黑水城地区的土地以买卖、典当、租赁的形式流转。通过流转,土地被寺庙和大地主兼并。寺庙和大地主利用经济上的优势,通过粮食借贷的高息、土地和牲畜租赁的高额租金,迫使农民破产,不得不低价卖掉土地。西夏法律对土地流转的规制有利于处在经济强势地位一方的寺庙和大地主。土地的流失使西夏晚期的社会矛盾突出,是西夏衰亡的原因之一。

关键词：土地流转契约黑水城西夏

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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