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Integrated neural tracing and in-situ barcoded sequencing reveals the logic of SCN efferent circuits in regulating circadian behaviors

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Science China(Life Sciences) 2024年第3期67卷 518-528页

作者： Meimei Liao xinwei gao Chen Chen Qi Li Qingchun Guo He Huang Erquan Zhang Dapeng Ju College of Biological Sciences China Agriculture UniversityBeijing 100193China National Institute of Biological Sciences(NIBS) Beijing 102206China Chinese Institute for Brain Research Beijing 102206China School of Biomedical Engineering Capital Medical UniversityBeijing 100069China Department of Anesthesiology The Second Affiliated HospitalChongqing Medical UniversityChongqing 401336China Tsinghua Institute of Multidisciplinary Biomedical Research Tsinghua UniversityBeijing 102206China

The circadian clock coordinates rhythms in numerous physiological processes to maintain organismal homeostasis. Since the suprachiasmatic nucleus(SCN) is widely accepted as the circadian pacemaker, it is critical to understand the neural mechanisms by which rhythmic information is transferred from the SCN to peripheral clocks. Here, we present the first comprehensive map of SCN efferent connections and suggest a molecular logic underlying these projections. The SCN projects broadly to most major regions of the brain, rather than solely to the hypothalamus and thalamus. The efferent projections from different subtypes of SCN neurons vary in distance and intensity, and blocking synaptic transmission of these circuits affects circadian rhythms in locomotion and feeding to different extents. We also developed a barcoding system to integrate retrograde tracing with in-situ sequencing, allowing us to link circuit anatomy and spatial patterns of gene expression. Analyses using this system revealed that brain regions functioning downstream of the SCN receive input from multiple neuropeptidergic cell types within the SCN, and that individual SCN neurons generally project to a single downstream brain region.This map of SCN efferent connections provides a critical foundation for future investigations into the neural circuits underlying SCNmediated rhythms in physiology. Further, our new barcoded tracing method provides a tool for revealing the molecular logic of neuronal circuits within heterogeneous brain regions.

关键词： circadian rhythms SCN output circuit neural tracing barcoded GFP in situ sequencing

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Characterization of the effects of hyaluronan oligosaccharides on human gut microbiota using a simulated batch fermentation system

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Food Science and Human Wellness 2024年

作者： xinwei gao Hongkang Zhu Litao Hu Jieyu Sun Wenjie Zuo Ping Liu Yang Wang Guocheng Du Zhen Kang The Science Center for Future Foods Jiangnan University The Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education Jiangnan University The Key Laboratory of Industrial Biotechnology Ministry of Education School of Biotechnology Jiangnan University School of Food Science and Technology Jiangnan University

The prebiotic effects of hyaluronan (HA) are widely recognized， contributing to improved gut health and immune modulation. Despite its extensive use as dietary supplement， the specific interactions between HA oligosaccharides (o-HAs) and the gut microbiome remain largely unexplored. To investigate its role and metabolic fate in gut homeostasis， 200 mg/day of o-HAs (average molecule weight 1k Da) were added to an automated computer-controlled SIMulator of the Gastrointestinal tract (SIMGI). The results revealed a significant reshaping of the intestinal flora composition by o-HAs， notably reducing the Firmicutes/Bacteroides ratio. Fermentation of o-HAs by gut microbiota significantly increased the abundance of Bifidobacteria， Prevotellaceae＿Prevotella， Dialister， Eubacterium， and Sutterella， but decreased that of Catenibacterium， Oscillospira， Klebsiella， and Citrobacter (P < 0.05). This corresponded with significant enhancements in the content of short-chain fatty acids (SCFAs) such as acetic acid， propionic acid and n-butyric acid， highlighting the significant impact of o-HAs at the genus level. Furthermore， analysis of microbial function predicted the downregulation of pathological events in nine human diseases， particularly infectious ones (parasitic and bacterial). Potential inhibitions were observed in metabolic pathways associated with pentose and glucuronate interconversions as well as cationic antimicrobial peptide resistance. These findings underscore the in vitro prebiotic effects of o-HAs and their potential relevance in managing diverticular diseases or preventing metabolic disorders through the regulation of gut microbiota.

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Influencing Factors of Healthy Aging Risk Assessed Using Biomarkers:A Life Course Perspective

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China CDC weekly 2024年第11期6卷 219-224,I0014-I0017页

作者： Cedric Zhang Bo Lua Yajie gao Jinming Li Xingqi Cao xinwei Lyu Yinuo Tu Shuyi Jin Zuyun Liu Center for Clinical Big Data and Analytics of the Second Affiliated Hospital and Department of Big Data in Health Science School of Public Healththe Key Laboratory of Intelligent Preventive Medicine of Zhejiang ProvinceZhejiang University School of MedicineHangzhou CityZhejiang ProvinceChina Institute of Epidemiology and Health Care University College LondonLondonUK College of Chemical and Biological Engineering Zhejiang UniversityHangzhou CityZhejiang ProvinceChina

Assessing individual risks of healthy aging using biomarkers and identifying associated factors have become important areas of research.In this study,we conducted a literature review of relevant publications between 2018 and 2023 in both Chinese and English databases.Previous studies have predominantly used single biomarkers,such as C-reactive protein,or focused on specific life course stages and factors such as socioeconomic status,mental health,educational levels,and unhealthy lifestyles.By summarizing the progress in this field,our study provides valuable insights and future directions for promoting healthy aging from a life course perspective.

关键词： such insight directions

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All-fiber-transmission photometry for simultaneous optogenetic stimulation and multi-color neuronal activity recording

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Opto-Electronic Advances 2022年第12期5卷 20-34,F0004页

作者： Zhongyang Qi Qingchun Guo Shu Wang Mingyue Jia xinwei gao Minmin Luo Ling Fu Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and TechnologyWuhan 430074China MoE Key Laboratory for Biomedical Photonics School of Engineering SciencesHuazhong University of Science and TechnologyWuhan 430074China National Institute of Biological Sciences Beijing 102206China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine Beijing 100191China School of Biomedical Engineering Capital Medical UniversityBeijing 100069China Chinese Institute for Brain Research Beijing 102206China School of Life Sciences Tsinghua UniversityBeijing 100084China

Manipulating and real-time monitoring of neuronal activities with cell-type specificity and precise spatiotemporal resolution during animal behavior are fundamental technologies for exploring the functional connectivity, information transmission, and physiological functions of neural circuits in vivo. However, current techniques for optogenetic stimulation and neuronal activity recording mostly operate independently. Here, we report an all-fiber-transmission photometry system for simultaneous optogenetic manipulation and multi-color recording of neuronal activities and the neurotransmitter release in a freely moving animal. We have designed and manufactured a wavelength-independent multi-branch fiber bundle to enable simultaneous optogenetic manipulation and multi-color recording at different wavelengths. Further, we combine a laser of narrow linewidth with the lock-in amplification method to suppress the optogenetic stimulation-induced artifacts and channel crosstalk. We show that the collection efficiency of our system outperforms a traditional epi-fluorescence system. Further, we demonstrate successful recording of dynamic dopamine(DA) responses to unexpected rewards in the nucleus accumbens(NAc) in a freely moving mouse. We also show simultaneous dual-color recording of neuronal Ca2+ signals and DA dynamics in the NAc upon delivering an unexpected reward and the simultaneous optogenetic activating at dopaminergic terminals in the same location. Thus, our multi-function fiber photometry system provides a compatible, efficient, and flexible solution for neuroscientists to study neural circuits and neurological diseases.

关键词： fiber photometry all-fiber-transmission multi-color optogenetic neuroscience

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A neuropsin-based optogenetic tool for precise control of Gq signaling

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Science China(Life Sciences) 2022年第7期65卷 1271-1284页

作者： Ruicheng Dai Tao Yu Danwei Weng Heng Li Yuting Cui Zhaofa Wu Qingchun Guo Haiyue Zou Wenting Wu xinwei gao Zhongyang Qi Yuqi Ren Shu Wang Yulong Li Minmin Luo National Institute of Biological Sciences(NIBS) Beijing 102206China School of Life Sciences Tsinghua UniversityBeijing 100084China School of Life Sciences Peking UniversityBeijing 100871China Graduate School of Peking Union Medical College Beijing 100730China Chinese Institute for Brain Research Beijing 102206China Tsinghua Institute of Multidisciplinary Biomedical Research(TIMBR) Beijing 102206China Peking University-Tsinghua University-NIBS Joint Graduate Program NIBSBeijing 102206China State Key Laboratory of Membrane Biology Peking University School of Life SciencesBeijing 100871China PKU-McGovern Institute for Brain Research Beijing 100871China Capital Medical University Beijing 102206China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China

G_(q)-coupled receptors regulate numerous physiological processes by activating enzymes and inducing intracellular Ca^(2+)signals.There is a strong need for an optogenetic tool that enables powerful experimental control over G_(q) signaling.Here,we present chicken opsin 5(cOpn5)as the long sought-after,single-component optogenetic tool that mediates ultra-sensitive optical control of intracellular G_(q) signaling with high temporal and spatial resolution.Expressing cOpn5 in HEK 293T cells and primary mouse astrocytes enables blue light-triggered,G_(q)-dependent Ca^(2+) release from intracellular stores and protein kinase C activation.Strong Ca^(2+) transients were evoked by brief light pulses of merely 10 ms duration and at 3 orders lower light intensity of that for common optogenetic tools.Photostimulation of cOpn5-expressing cells at the subcellular and single-cell levels generated fast intracellular Ca^(2+)transition,thus demonstrating the high spatial precision of cOpn5 optogenetics.The cOpn5-mediated optogenetics could also be applied to activate neurons and control animal behavior in a circuit-dependent manner.cOpn5 optogenetics may find broad applications in studying the mechanisms and functional relevance of G_(q) signaling in both non-excitable cells and excitable cells in all major organ systems.

关键词： chicken opsin 5 astrocytes photostimulation Ca^(2+)imaging IP3 protein kinase C neural circuit

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融合支持向量机和特征降维方法的人-椅系统振动模型研究

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声学学报 2024年第2期49卷 217-225页

作者：王新伟张筱璐林森高宇欣北京工业大学机械与能源工程学院北京100124

人-椅系统的振动传递特性受人体体征参数、座椅结构、乘坐环境等多种复杂因素影响。在人体振动实验研究的基础上,寻求构建一种基于支持向量机回归的座椅频响函数预测模型,分别采用递归特征消除法和主成分分析法对人体体征参数进行降维,... 详细信息

人-椅系统的振动传递特性受人体体征参数、座椅结构、乘坐环境等多种复杂因素影响。在人体振动实验研究的基础上,寻求构建一种基于支持向量机回归的座椅频响函数预测模型,分别采用递归特征消除法和主成分分析法对人体体征参数进行降维,并将低维特征输入预测模型,以实现对人-椅系统频响函数及其正交轴效应的预测。结果显示,相比传统支持向量机回归模型,应用主成分分析法降低体征参数关联,可以显著降低模型预测误差,预测值与实测值拟合度可达92%。通过递归特征消除法剔除次要体征参数,可进一步提升预测精度,预测值与实测值拟合度达94%。研究表明,基于特征降维优化的支持向量机回归预测模型能够有效筛选人体振动模型中输入参数的冗余信息,并提升座椅频响函数的计算效率和预测精度。

关键词：人-椅系统支持向量回归递归特征消除主成分分析

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Integrated neural tracing and in-situ barcoded sequencing reveals the logic of SCN efferent circuits in regulating circadian behaviors

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Science China Life Sciences 2023年

作者： Meimei Liao xinwei gao Chen Chen Qi Li Qingchun Guo He Huang Erquan Zhang Dapeng Ju Tsinghua Institute of Multidisciplinary Biomedical Research Tsinghua University Department of Anesthesiology The Second Affiliated Hospital Chongqing Medical University College of Biological Sciences China Agriculture University School of Biomedical Engineering Capital Medical University National Institute of Biological Sciences (NIBS) Chinese Institute for Brain Research

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影响岩溶热储采出温度的开采参数敏感性研究——以河南清丰地区为例

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煤田地质与勘探 2024年第1期52卷 83-92页

作者：韩昀李克文何继富汪新伟高楠安中国地质大学(北京)能源学院北京100083 非常规天然气地质评价与开发工程北京市重点实验室北京100083 中石化新星(北京)新能源研究院有限公司北京100083 中国石化地热资源开发利用重点实验室北京100083

采出温度是影响地热能有效利用率的关键指标,采出温度越高,热储开发效果越好。岩溶热储作为一种重要的地热储层类型,其采出温度受到储层参数的影响。以河南清丰地热田奥陶系岩溶热储为例,通过建立热储地质模型并利用7口地热井资料,进行... 详细信息

采出温度是影响地热能有效利用率的关键指标,采出温度越高,热储开发效果越好。岩溶热储作为一种重要的地热储层类型,其采出温度受到储层参数的影响。以河南清丰地热田奥陶系岩溶热储为例,通过建立热储地质模型并利用7口地热井资料,进行基于热流和井储耦合的数值模拟研究,探讨储层地质条件和回灌参数对采出温度的影响。研究结果发现,断层的存在加速了热储中低温区向生产井的扩散,导致热突破时间的提前。在开采后期,有断层情况下采出温度较高,且变化曲线斜率远高于无断层情况,表明断层有助于提高清丰地区热平衡时的采出温度,最终有利于增加采热量。目前,一般认为,注采井距越小采出温度越低。但是,当回灌速率高于50 kg/s时,随着开采时间的增加,采出温度呈现快速下降趋势,注采井距835 m下的采出温度甚至高于1000 m的情况。最后,确定清丰地区特定场景下的最优回灌参数组合为:回灌温度20℃、回灌速率50 kg/s、注采井距835 m。本研究结果将为清丰地区或其他类似岩溶热储开发方案的制定提供有益指导。

关键词：岩溶热储回灌参数采出温度耦合断层数值模拟

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基于GTWR的站域建成环境对城市轨道交通客流量的时空影响

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北京工业大学学报 2024年第6期50卷 724-732页

作者：朱敏清高洁崔洪军马新卫河北工业大学建筑与艺术设计学院天津300130 河北工业大学土木与交通学院天津300401

轨道交通客流量影响因素是轨道交通方面研究的一个关注点,不同站点客流量的时空非平稳性被认为与站域建成环境有关。通过构建时空地理加权(geographically and temporally weighted regression,GTWR)模型,揭示了土地多样性、密度、站点... 详细信息

轨道交通客流量影响因素是轨道交通方面研究的一个关注点,不同站点客流量的时空非平稳性被认为与站域建成环境有关。通过构建时空地理加权(geographically and temporally weighted regression,GTWR)模型,揭示了土地多样性、密度、站点属性3个方面因素在时间和空间维度上对天津市轨道交通客流量的影响。结果表明:相较于传统的地理加权(geographically weighted regression,GWR)模型和最小二乘法(ordinary least squares,OLS)模型,GTWR具有更好的拟合优度;公交站点密度对轨道交通客流产生促进作用,尤其在工作日的早晚高峰时段和中心城区位置;市中心的商业设施在工作日晚高峰吸引更多的地铁乘客,而在近郊区它们在早高峰吸引更多的地铁乘客;人口密度促进轨道交通的客流量;充足的停车场设施数量可以吸引更多的轨道交通乘客。

关键词：时空地理加权模型(GTWR) 建成环境轨道交通自动售检票系统(AFC)数据时空异质性天津市城市轨道交通

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“大气污染物和温室气体协同控制”政策的实施效果研究

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南京财经大学学报 2024年第3期 12-22页

作者：刘娜杨斯悦高新伟中国石油大学(华东)经济管理学院山东青岛266580 西北工业大学公共政策与管理学院陕西西安710072

推动减污降碳协同增效是深入打好污染防治攻坚战,实现碳达峰的必然要求。将《大气污染防治行动计划》和《打赢蓝天保卫战三年行动计划》视为一个连贯政策,运用渐进双重差分法探究了于2015和2018年提出的“大气污染物和温室气体协同控制... 详细信息

推动减污降碳协同增效是深入打好污染防治攻坚战,实现碳达峰的必然要求。将《大气污染防治行动计划》和《打赢蓝天保卫战三年行动计划》视为一个连贯政策,运用渐进双重差分法探究了于2015和2018年提出的“大气污染物和温室气体协同控制”政策实施效果。研究表明:“大气污染物和温室气体协同控制”政策显著提高了“SO_(2)-CO_(2)”排放强度协同度和“PM-CO_(2)”排放量(强度)协同度,但该政策对“SO_(2)-CO_(2)”排放量协同度无显著影响。机制分析表明,提升政府监管水平、弱化政企关系以及增强企业绿色创新是政策的主要传导机制。异质性分析表明,政策效果在不同能耗水平的城市中具有显著差异,比起高污染上市公司,高耗能中小企业在污染物和CO_(2)的协同减排措施上仍存在较大改善空间。研究结论对我国优化“持续深入打好蓝天保卫战”相关政策提供启示。

关键词：大气十条蓝天三年减污降碳协同度渐进双重差分

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