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TRPC3 plays a role in the neural differentiation of mouse embryonic stem cells and cell survival

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TRPC3 plays a role in the neural differentiation of mouse em...

Massive Files Prefetching Model Based on LSTM Neural Network with Cache Transaction Strategy

第十一届全国钙信号和细胞功能研讨会

作者： helen baixia hao Sarah E.Webb Marc Moreau Catherine Leclerc Jianbo Yue Andrew L. Miller Division of Life Science and State Key Laboratory of Molecular Neuroscience HKUST Centre de Biologie du Développement UMR-CNRS 5547 and GDR2688 Université Toulouse III Department of Biomedical Sciences City University of Hong Kong

The neural differentiation of embryonic stem cells(ESCs) is a dynamic and complex process, which has been shown to be regulated by several different signaling pathways. Ca2+is a highly versatile intra-and intercellular second messenger, has been reported to be involved in several of these regulatory pathways. Thus, by inference we hypothesized that Ca2+ may play an important role in regulating neural differentiation of ESCs. The goal of our research was, therefore, to investigate the role of canonical transient receptor potential channel subtype 3(TRPC3), a cation channel that is permeable to both Ca2+ and Na+, in the regulation of the neural differentiation of mouse ESCs(m ESCs). We demonstrate that TRPC3 is expressed in m ESCs and that it contributes to store-operated Ca2+ entry(SOCE) in these cells following treatment with thapsigargin. We also show that the level of TRPC3 expression gradually increases as m ESCs differentiate into cells of the neural lineage. sh RNA knockdown of TRPC3 suppressed its expression by 0% and led to a reduction in the expression of the neural differentiation markers: nestin, sox1 and tuj1. Furthermore, treatment of m ESCs with the TRPC3 inhibitor, pyr3, also inhibited the expression of these neural differentiation markers and reduced the amount of SOCE. Interestingly, TRPC3 knockout with CRISPR/Cas9, or inhibition with pyr3 also resulted in dramatic cell death during the early stages of m ESC-derived neural differentiation. Taken together, TRPC3 appears to positively regulate the neural differentiation of m ESCs and it is also appears to be required for cell survival during this process. We are now studying how the suppression of TRPC3 affects the cellular and molecular mechanisms involved in the inhibition of neural differentiation and cell survival.

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Computers, Materials & Continua 2020年第5期63卷 979-993页

作者： Dongjie Zhu Haiwen Du Yundong Sun Xiaofang Li Rongning Qu hao Hu Shuangshuang Dong helen Min Zhou Ning Cao School of Computer Science and Technology Harbin Institute of TechnologyWeihai264209China School of Science Harbin Institute of TechnologyWeihai264209China School of Engineering Manukau Institute of TechnologyAuckland2241New Zealand College of Mathematics and Computer Science Xinyu UniversityXinyu338004China College of Information Engineering Sanming UniversitySanming365004China School of Astronautics Harbin Institute of TechnologyHarbin150001China

In distributed storage systems,file access efficiency has an important impact on the real-time nature of information *** a popular approach to improve file accessing efficiency,prefetching model can fetches data before it is needed according to the file access pattern,which can reduce the I/O waiting time and increase the system ***,prefetching model needs to mine the degree of association between files to ensure the accuracy of *** the massive small file situation,the sheer volume of files poses a challenge to the efficiency and accuracy of relevance *** this paper,we propose a massive files prefetching model based on LSTM neural network with cache transaction strategy to improve file access ***,we propose a file clustering algorithm based on temporal locality and spatial locality to reduce the computational ***,we propose a definition of cache transaction according to files occurrence in cache instead of time-offset distance based methods to extract file block feature ***,we innovatively propose a file access prediction algorithm based on LSTM neural network which predict the file that have high possibility to be *** show that compared with the traditional LRU and the plain grouping methods,the proposed model notably increase the cache hit rate and effectively reduces the I/O wait time.

关键词： Massive files prefetching model cache transaction distributed storage systems LSTM neural network

Lenvatinib-and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer

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Acta Pharmaceutica Sinica B 2022年第9期12卷 3726-3738页

作者： Chao Zheng Wen Zhang Jinming Wang Yihui Zha Fengqin Xiong Ying Cai Xiang Gong Binyu Zhu helen He Zhu hao Wang Yaping Li Pengcheng Zhang China State Institute of Pharmaceutical Industry Shanghai 201203China State Key Laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Yantai Key Laboratory of Nanomedicine&Advanced Preparations Yantai Institute of Materia MedicaYantai 264000China State Key Laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200135China University of Chinese Academy of Sciences Beijing 100049China Bohai Rim Advanced Research Institute for Drug Discovery Yantai 264000China

Metastatic triple-negative breast cancer(TNBC)is the most aggressive type of breast *** of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes(CTLs)and the accumulation of immunosuppressive ***,we designed a lenvatinib-and vadimezan-loaded synthetic high-density lipoprotein(LV-sHDL)for combinational immunochemotherapy of metastatic *** LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous *** multitargeted tyrosine kinase inhibitor(TKI)lenvatinib induced immunogenic cell death of the cancer cells,and the stimulator of interferon genes(STING)agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation,which synergistically improved the intratumoral infiltration of total and active CTLs by 33-and 13-fold,***-sHDL inhibited the growth of orthotopic 4T1 tumors,reduced pulmonary metastasis,and prolonged the survival of *** efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand *** study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

关键词： High-density lipoprotein Immunotherapy Combination therapy Metastasis Triple-negative breast cancer Lenvatinib Vadimezan Immune checkpoint blockad

Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membranedecorated nanoparticles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3218-3231页

作者： Wen Zhang Yihui Zhai Ying Cai Xiang Gong Yunxuan Jiang Rong Rong Chao Zheng Binyu Zhu helen He Zhu hao Wang Yaping Li Pengcheng Zhang China State Institute of Pharmaceutical Industry Shanghai 201203China State Key Laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Biomedical Engineering&State Key Laboratory of Advanced Medical Materials and Devices ShanghaiTech UniversityShanghai 201210China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Yantai Institute of Materia Medica Shandong 264000China State Key Laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127China University of Chinese Academy of Sciences Beijing 100049China

Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocompatibility complex I(MHC-I)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-I-deficient *** on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer *** released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 *** also block CD47-mediated phagocytosis *** inhibit the growth of MHC-I-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important *** macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophagemediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

关键词： MHC-I deficiency Macrophage CD47 Immunotherapy Triple-negative breast cancer Phagocytosis Immune checkpoint Innate immunity

Grading the Severity of Mispronunciations in CAPT Based on Statistical Analysis and Computational Speech Perception

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Journal of Computer Science & Technology 2014年第5期29卷 751-761页

作者：贾珈梁伟俭吴育昊张秀龙王昊蔡莲红蒙美玲 Department of Computer Science and Technology Tsinghua University Tsinghua National Laboratory for Information Science and Technology Tsinghua University Key Laboratory of Pervasive Computing Ministry of Education Human-Computer Communications Laboratory Department of Systems Engineering and Engineering Management The Chinese University of Hong Kong Tsinghua-CUHK Joint Research Center for Media Sciences Technologies and Systems

Computer-aided pronunciation training（CAPT） technologies enable the use of automatic speech recognition to detect mispronunciations in second language（L2） learners＇ speech. In order to further facilitate learning, we aim to develop a principle-based method for generating a gradation of the severity of mispronunciations. This paper presents an approach towards gradation that is motivated by auditory perception. We have developed a computational method for generating a perceptual distance（PD） between two spoken phonemes. This is used to compute the auditory confusion of native language（L1）. PD is found to correlate well with the mispronunciations detected in CAPT system for Chinese learners of English,i.e., L1 being Chinese（Mandarin and Cantonese） and L2 being US English. The results show that auditory confusion is indicative of pronunciation confusions in L2 learning. PD can also be used to help us grade the severity of errors（i.e.,mispronunciations that confuse more distant phonemes are more severe） and accordingly prioritize the order of corrective feedback generated for the learners.

关键词： second language learning computer-aided pronunciation training mispronunciation computational speech perception

Breakthrough cancer medicine and its impact on novel drug development in China: report of the US Chinese Anti-Cancer Association (USCACA) and Chinese Society of Clinical Oncology (CSCO) Joint Session at the 17th CSCO Annual Meeting

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Chinese Journal of Cancer 2014年第12期33卷 620-624页

作者： Feng Roger Luo Jian Ding helen X. Chen hao Liu Man-Cheong Fung Maria Koehler Jean Pierre Armand Lei Jiang Xiao Xu Ge Zhang Li Xu Pascal Qian Li Yan The US Chinese Anti-Cancer Association MartinezCA 94553 USA Department of Oncology Janssen Research & Development LLC RaritanNJ 08869 USA Shanghai Institute of Materia Medica Chinese Academy of Sciences Cancer Therapy Evaluation Program National Cancer Institute Novartis Pharmaceuticals (China) Oncology Pfizer Oncology New YorkNY 10017 USA Institut Gustave Roussy Cancer Campus Grand Paris ACEA Biosciences Inc. Jiangsu Hengrui Medicine Co. Ltd. Beijing Cancer Hospital and Institute Peking University School of Oncology

The US Chinese Anti-Cancer Association(USCACA)teamed up with Chinese Society of Clinical Oncology(CSCO)to host a joint session at the17th CSCO Annual Meeting on September 20th,2014in Xiamen,*** a focus on breakthrough cancer medicines,the session featured innovative approaches to evaluate breakthrough agents and established a platform to interactively share successful experiences from case studies of 6 novel agents from both the United States and *** goal of the session is to inspire scientific and practical considerations for clinical trial design and strategy to expedite cancer drug development in China.A panel discussion further provided in-depth advice on advancing both early and full development of novel cancer medicines in China.

关键词：抗癌药物中国临床美国学会肿瘤协会新药

Attitudes towards suicide attempts broadcast on social media: an exploratory study of Chinese microblogs

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Attitudes towards suicide attempts broadcast on social media...

第二十届全国心理学学术会议--心理学与国民心理健康

作者： Ang Li Xiaoxiao Huang Bibo hao Bridianne O‘Dea helen Christensen Tingshao Zhu Department of Psychology Beijing Forestry University Black Dog Institute University of New South Wales Institute of Psychology Chinese Academy of Sciences School of Computer and Control University of Chinese Academy of Sciences

Introduction. Broadcasting a suicide attempt on social media has become a public health concern in many countries, particularly in China. In these cases, social media users are likely to be the firstto witness the suicide attempt, and their attitudes may determine their likelihood of joining rescue efforts. This paper examines Chinese social media(Weibo) users’ attitudes towards suicide attempts broadcast on ***. A total of 4,969 Weibo posts were selected from a customised Weibo User Pool which consisted of 1.06 million active users. The selected posts were then independently coded by two researchers using a coding framework that assessed:(a) Themes,(b) General attitudes,(c) Stigmatising attitudes,(d) Perceived motivations, and(e) Desired *** and Discussion. More than one third of Weibo posts were coded as "stigmatising"(35%). Among these, 22%, 16%, and 15% of posts were coded as "deceitful", "pathetic", and "stupid", respectively. Among the posts which reflected different types of perceived motivations, 57% of posts were coded as "seeking attention". Among the posts which reflected desired responses, 37% were "not saving" and 28% were "encouraging suicide". Furthermore, among the posts with negative desired responses(i.e. "not saving" and "encouraging suicide"), 57% and 17% of them were related to different types of stigmatising attitudes and perceived motivations respectively. Specifically, 29% and 26% of posts reflecting both stigmatising attitudes and negative desired responses were coded as "deceitful" and "pathetic" respectively;while, 66% of posts reflecting both perceived motivations and negative desired responses were coded as "seeking attention". Very few posts "promoted literacy"(2%) or "provided resources"(8%). Gender differences existed in multiple ***. This paper confirms the need for stigma reduction campaigns for Chinese social media users to improve their attitudes towards those who broadcast their suicide

关键词： Suicide Social media Stigma Weibo Microblog China

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加快京津冀都市圈经济一体化的对策研究

科技和产业 2006年第11期6卷 16-17,21页

作者：李灏冯百侠王宏剑河北理工大学经济管理学院唐山063009

区域经济一体化是市场经济发展的大趋势,当前,我国的区域经济一体化发展也初见端倪。本文结合京津冀都市圈经济一体化进程中存在的问题,从跨区域协调机制、产业结构、交通体系和水资源环境等方面提出了加快京津冀都市圈经济一体化的思... 详细信息

区域经济一体化是市场经济发展的大趋势,当前,我国的区域经济一体化发展也初见端倪。本文结合京津冀都市圈经济一体化进程中存在的问题,从跨区域协调机制、产业结构、交通体系和水资源环境等方面提出了加快京津冀都市圈经济一体化的思路和对策。

关键词：经济一体化京津冀都市圈对策

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唐山市发展休闲产业的SWOT分析

科技和产业 2006年第11期6卷 13-15页

作者：王宏剑冯百侠李灏河北理工大学经济管理学院唐山063009

休闲产业是城市经济发展中的一个重要的新的增长点,对城市的发展有重要的推动作用。本文采用SWOT法分析唐山市发展休闲产业的优势、劣势、机会、挑战,有助于探索唐山市发展休闲产业的途径。

关键词：唐山市休闲产业 SWOT分析