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Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma yiren Cao Shi Yan Panpan zhang Lixin Zhou Qimin Zhan Nan Wu Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International Cancer Institute Beijing 100191China Institute of Cancer Research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer *** mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting ***,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of *** analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based *** expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of ***16 binds to HBB and promotes HBB accumulation by inhibiting ***16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the ***,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in ***,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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Correction of a CADASIL point mutation using adenine base editors in hiPsCsandbloodvessel organoids

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Journal of Genetics and Genomics 2024年第2期51卷 197-207页

作者： Jingwen Wang Lei zhang Guanglan Wu Jinni Wu Xinyao Zhou Xiaolin Chen Yongxia Niu yiren Jiao Qianyi Liu Puping Liang Guang Shi Xueqing Wu Junjiu Huang MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China Key Laboratory of Reproductive Medicine of Guangdong Province The First Affiliated Hospital and School of Life SciencesSun Yat-sen UniversityGuangzhouGuangdong 510275China Center of Reproductive Medicine Children's Hospital of Shanxi and Women Health Center of ShanxiTaiyuanShanxi 030013China

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic small vessel disease caused by mutations in the NOTCH3 gene. However, the pathogenesis of CADASIL remains unclear, and patients have limited treatment options. Here, we use human induced pluripotent stem cells (hiPSCs) generated from the peripheral blood mononuclear cells of a patient with CADASIL carrying a heterozygous NOTCH3 mutation (c.1261C>T, p.R421C) to develop a disease model. The correction efficiency of different adenine base editors (ABEs) is tested using the HEK293T-NOTCH3 reporter cell line. ABEmax is selected based on its higher efficiency and minimization of predicted off-target effects. Vascular smooth muscle cells (VSMCs) differentiated from CADASIL hiPSCs show NOTCH3 deposition and abnormal actin cytoskeleton structure, and the abnormalities are recovered in corrected hiPSC-derived VSMCs. Furthermore, CADASIL blood vessel organoids generated for in vivo modeling show altered expression of genes related to disease phenotypes, including the downregulation of cell adhesion, extracellular matrix organization, and vessel development. The dual adeno-associated virus (AAV) split-ABEmax system is applied to the genome editing of vascular organoids with an average editing efficiency of 8.82%. Collectively, we present potential genetic therapeutic strategies for patients with CADASIL using blood vessel organoids and the dual AAV split-ABEmax system.

关键词： CADASIL Induced pluripotent stem cells Adenine base editors AAV Blood vessel Organoid

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Scenic Investigation and Assessment of Nature Reserves in Beijing

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Chinese Forestry Science and Technology 2005年第4期4卷 60-67页

作者： CAO Juan LIANG yiren zhang Junhua Editorial Department Chinese Landscape Architecture Magazine Beijing 100835 P.R.China College of Landscape Architecture Beijing Forestry University Beijing100083 P.R.China School of Architecture Tsinghua University Beijing 100084 P.R.China

This paper focuses on a detailed investigation and assessment by choosing seven nature reserves with SD (semantic differential). The samples are chosen from the photos obtained in the investigation, and questionnaires are made according to SD. Through the factor analysis of the data from questionnaires, an assessment curve of the samples is drawn, and space coordinate is concluded. The advantages and disadvantages are also discussed.

关键词： landscape architecture nature reserve investigation evaluation semantic differential factoranalysis

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-94 G/A polymorphism in the dopamine D1 receptor gene is associated with schizophrenia in a Chinese Han population from Shandong province

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Neural Regeneration Research 2011年第19期6卷 1484-1487页

作者： Zhaoyun Du Guangxin Wang Yuebing zhang yiren Cheng Chuan'an Zhu Department of Laboratory Medicine Jining Medical College Jining 272067 Shandong Province China Institute of Pediatrics Qilu Children's Hospital Shandong University Jinan 250022 Shandong Province China Department of Psychiatry Second Affiliated Hospital of Jining Medical College Jining 272051 Shandong Province China Department of Laboratory First People's Hospital of Jining Jining 272001 Shandong Province China

The correlation between -94 G/A polymorphism in the dopamine D1 receptor gone and schizophrenia remains poorly understood despite extensive research. This study sought to evaluate the genotypes and allele frequencies of the -94 G/A polymorphism in the dopamine D1 receptor gone by real-time PCR using TaqMan fluorescent probes. One hundred and sixty-two patients with schizophrenia and 101 healthy controls living in Shandong province of China were evaluated. Experimental results showed that the G/A genotype distribution was significantly higher in the schizophrenia patients than in healthy controls. The frequencies of G allele and A allele were not significantly different between the schizophrenia patients and the controls. Thus, the -94 G/A polymorphism in the dopamine D1 receptor gone was found to be associated with schizophrenia in a Chinese Han population from Shandong province.

关键词： dopamine D1 receptor gone single nucleotide polymorphism schizophrenia

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A cell transcriptomic profile p ovides insights into adipocytes of porcine mammary gland across development

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Journal of Animal Science and Biotechnology 2024年第1期15卷 182-200页

作者： Yongliang Fan Long Jin Zhiping He Tiantian Wei Tingting Luo Jiaman zhang Can Liu Changjiu Dai Chao A Yan Liang Xuan Tao Xuebin Lv yiren Gu Mingzhou Li State Key Laboratory of Swine and Poultry Breeding Industry College of Animal Science and TechnologySichuan Agricultural UniversityChengdu 611130China Key Laboratory of Qinghai‑Tibetan Plateau Animal Genetic Resource Reservation and Utilization Southwest Minzu UniversityChengdu 610041China Animal Breeding and Genetics Key Laboratory of Sichuan Province Sichuan Animal Science AcademyChengdu 610000China

Background Studying the composition and developmental mechanisms in mammary gland is crucial for healthy growth of newborns. The mammary gland is inherently heterogeneous, and its physiological function dependents on the gene expression of multiple cell types. Most studies focused on epithelial cells, disregarding the role of neighboring *** Here, we constructed the largest transcriptomic dataset of porcine mammary gland cells thus far. The dataset captured 126,829 high-quality nuclei from physiological mammary glands across five developmental stages(d 90 of gestation, G90;d 0 after lactation, L0;d 20 after lactation, L20;2 d post natural involution, PI2;7 d post natural involution, PI7). Seven cell types were identified, including epithelial cells, adipocytes, endothelial cells, fibroblasts cells, immune cells, myoepithelial cells and precursor cells. Our data indicate that mammary glands at different developmental stages have distinct phenotypic and transcriptional signatures. During late gestation(G90), the differentiation and proliferation of adipocytes were inhibited. Meanwhile, partly epithelial cells were completely differentiated. Pseudo-time analysis showed that epithelial cells undergo three stages to achieve lactation, including cellular differentiation, hormone sensing, and metabolic activation. During lactation(L0 and L20), adipocytes area accounts for less than 0.5% of mammary glands. To maintain their own survival, the adipocyte exhibited a poorly differentiated state and a proliferative capacity. Epithelial cells initiate lactation upon hormonal stimulation. After fulfilling lactation mission, their undergo physiological death under high intensity lactation. Interestingly, the physiological dead cells seem to be actively cleared by immune cells via CCL21-ACKR4 pathway. This biological process may be an important mechanism for maintaining homeostasis of the mammary gland. During natural involution(PI2 and PI7), epithelial cell populatio

关键词： Adipocytes Cell–cell interaction Development Mammary gland snRNA-seq

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Effect of ZSM-5 zeolite morphology on the catalytic performance of the alkylation of toluene with methanol

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Journal of Energy Chemistry 2014年第4期23卷 491-497页

作者： Hongyu Wu Min Liu Wei Tan Keke Hou Anfeng zhang yiren Wang Xinwen Guo State Key Laboratory of Fine Chemicals Department of Catalysis Chemistry and Engineering School of Chemical EngineeringDalian University of Technology

A series of ZSM-5 zeolites, with the morphologies of sphere, sphere with cubic particles on the surface, and cubic particles, were synthesized by hydrothermal method using n-butylamine as the template, assisted by the addition of NaC1 and crystal seed. X-ray diffraction （XRD）, scanning electron microscope （SEM）, X-ray fluorescence （XRF） and temperature-programmed desorption of ammonia （NH3-TPD） were used to characterize these samples. The samples were tested with toluene methylation reaction. The modified sample composed of spherical particles with 3 μm crystal particles on the surface had a para-xylene selectivity of 95% and maintained 79% of the initial conversion after running the reaction for 50 h. This modified samole showed the best stability amonz the tested three modified samoles.

关键词： alkylation toluene methanol morphology ZSM-5

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In-flight calibration of the magnetometer on the Mars orbiter of Tianwen-1

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Science China(Technological Sciences) 2023年第8期66卷 2396-2405页

作者： ZOU ZhuXuan WANG YuMing zhang TieLong WANG GuoQiang XIAO SuDong PAN ZongHao zhang ZhouBin YAN Wei DU Yang CHI YuTian CHENG Long WU ZhiYong HAO XinJun LI yiren LIU Kai CHEN ManMing SU ZhenPeng SHEN ChengLong XU MengJiao GUO JingNan School of Earth and Space Sciences/Deep Space Exploration Laboratory University of Science and Technology of ChinaHefei 230026China CAS Center for Excellence in Comparative Planetology/CAS Key Laboratory of Geospace Environment/Mengcheng National Geophysical Observatory University of Science and Technology of ChinaHefei 230026China Space Research Institute Austrian Academy of SciencesGraz 8010Austria Institute of Space Science and Applied Technology Harbin Institute of TechnologyShenzhen 518055China National Astronomical Observatories Chinese Academy of SciencesBeijing 100080China Shanghai Institute of Satellite Engineering Shanghai 200240China Institute of Deep Space Sciences Deep Space Exploration LaboratoryHefei 230026China

Mars orbiter magnetometer(MOMAG)is one of seven science payloads onboard Tianwen-1’s *** most of the satellites,Tianwen-1’s orbiter is not magnetically cleaned,and the boom where placed the magnetometer’s sensors is not long *** pose many challenges to the magnetic field data *** this study,we introduce the in-flight calibration process of the Tianwen-1/*** magnetic interference including spacecraft generated dynamic field and the slowlychanging zero offsets are cleaned in *** the calibrated magnetic field data are compared with the data from the Mars atmosphere and volatile Evolutio N(MAVEN).We find that some physical structures in the solar wind are consistent between the two data sets,and the distributions of the magnetic field strength in the solar wind are very *** results suggest that the in-flight calibration of the MOMAG is successful and the MOMAG provides reliable data for scientific research.

关键词： magnetometer in-flight calibration Martian magnetic field Tianwen-1

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The Mars orbiter magnetometer of Tianwen-1:in-flight performance and first science results

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Earth and Planetary Physics 2023年第2期7卷 216-228页

作者： YuMing Wang TieLong zhang GuoQiang Wang SuDong Xiao ZhuXuan Zou Long Cheng ZongHao Pan Kai Liu XinJun Hao yiren Li ManMing Chen ZhouBin zhang Wei Yan ZhenPeng Su ZhiYong Wu ChengLong Shen YuTian Chi MengJiao Xu JingNan Guo Yang Du School of Earth and Space Sciences/Deep Space Exploration Laboratory University of Science and Technology of ChinaHefei 230026China CAS Center for Excellence in Comparative Planetology/CAS Key Laboratory of Geospace Environment/Mengcheng National Geophysical Observatory University of Science and Technology of ChinaHefei 230026China Space Research Institute Austrian Academy of SciencesGrazAustria Institute of Space Science and Applied Technology Harbin Institute of TechnologyShenzhen 518055China National Astronomical Observatories Chinese Academy of SciencesBeijing 100012China Institute of Deep Space Sciences Deep Space Exploration LaboratoryHefei 230026China Shanghai Institute of Satellite Engineering Shanghai 201109China

The Mars Orbiter MAGnetometer(MOMAG)is a scientific instrument onboard the orbiter of China’s first mission for Mars—*** November 13,2021,it has been recording magnetic field data from the solar wind to the magnetic pile-up region surrounding *** we present its in-flight performance and first science results,based on its first one and one-half months’*** these early MOMAG observations to the magnetic field data in the solar wind from NASA’s Mars Atmosphere and Volatile EvolutioN(MAVEN)mission,we report that the MOMAG magnetic field data are at the same level in magnitude,and describe the same magnetic structures with similar variations in three *** recognize 158 clear bow shock(BS)crossings in these MOMAG data;their locations match well statistically with the modeled average *** also identify and compare five pairs of datasets collected when Tianwen-1’s orbiter and the MAVEN probe made simultaneous BS *** BS crossings confirm the global shape of modeled BS,as well as the south-north asymmetry of the Martian *** cases presented in this paper suggest that the BS is probably more dynamic at flank than near the *** far,MOMAG performs well,and provides accurate magnetic field *** is continuously scanning the magnetic field surrounding *** from MOMAG’s measurements complement data from MAVEN and will undoubt edly advance our understanding of the plasma environment of Mars.

关键词： Mars magnetic field Tianwen-1 magnetometer bow shock

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填料塔孔口型液体分布器液体穿孔流量系数实验研究

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化学工程 2000年第3期28卷 10-12,42页

作者：张剑慈董谊仁浙江工学院浙西分校衢州324004 浙江工业大学

在特制的实验装置中 ,针对填料塔孔口型液体分布器最常见的单孔流量范围 ,实验研究了 8种孔口的流量系数 Cd随孔口结构和雷诺数 Re的变化规律 ,从所得到的 5 0 8组 Cd- Re数据表明 ,各种孔口的 Cd 均与Re密切相关。Re大于 10 0 0 0 ,Cd... 详细信息

在特制的实验装置中 ,针对填料塔孔口型液体分布器最常见的单孔流量范围 ,实验研究了 8种孔口的流量系数 Cd随孔口结构和雷诺数 Re的变化规律 ,从所得到的 5 0 8组 Cd- Re数据表明 ,各种孔口的 Cd 均与Re密切相关。Re大于 10 0 0 0 ,Cd 为一恒定值 ,在 0 .6 1～ 0 .96范围 ,仅随孔口结构而变 ,Re小于 10 0 0 0 ,Cd呈现出急剧、复杂的变化。实际填料塔液体分布器孔口射流雷诺数多在 10 0 0 0以下。

关键词：填料塔液体分布器流量系数孔口型设计

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权重队列实时调度系统的反馈控制

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计算机工程 2007年第5期33卷 7-9,12页

作者：张军邹益仁中国科学院自动化研究所综合自动化工程研究中心北京100080

针对工作在不可预测环境下具有不确定性任务特征的实时调度系统的服务区分问题,利用队列理论对权重队列实时调度系统进行多变量控制建模,并结合模型预测控制方法将控制问题转化为受限多变量优化问题,进而基于标准的最小二乘求解器设计... 详细信息

针对工作在不可预测环境下具有不确定性任务特征的实时调度系统的服务区分问题,利用队列理论对权重队列实时调度系统进行多变量控制建模,并结合模型预测控制方法将控制问题转化为受限多变量优化问题,进而基于标准的最小二乘求解器设计预测控制调度框架以及算法。通过调整任务类的权重因子来改变任务类的计算资源分配,以实现为调度任务类提供相对延迟时间比保证。仿真试验结果表明,所设计方法在任务到达速率和执行时间变化且不能预知的情况下,仍然能为系统提供良好的相对延迟时间比控制。

关键词：实时调度延迟预测控制权重服务区分

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