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Long-term in vivo chimeric cells tracking in non-human primate

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Protein & Cell 2024年第3期15卷 207-222页

作者： Junmo Wu Yu Kang Xiang Luo Shaoxing Dai Yuxi Shi Zhuoyao Li Zengli Tang Zhenzhen Chen Ran Zhu Pengpeng Yang Zifan Li Hong Wang Xinglong Chen Ziyi Zhao Weizhi ji Yuyu Niu State Key Laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Yunnan Key Laboratory of Primate Biomedical Research Kunming 650500China faculty of life science and technology Kunming University of Science and TechnologyKunming 650500China

Non-human primates(NHPs)are increasingly used in preclinical trials to test the safety and efficacy of biotech-nology therapies.Nonetheless,given the ethical issues and costs associated with this model,it would be highly advantageous to use NHP cellular models in clinical studies.However,developing and maintaining the naive state of primate pluripotent stem cells(PSCs)remains difficult as does in vivo detection of PSCs,thus limiting biotech-nology application in the cynomolgus monkey.Here,we report a chemically defined,xeno-free culture system for culturing and deriving monkey PSCs in vitro.The cells display global gene expression and genome-wide hypometh-ylation patterns distinct from monkey-primed cells.We also found expression of signaling pathways components that may increase the potential for chimera formation.Crucially for biomedical applications,we were also able to integrate bioluminescent reporter genes into monkey PsCs and track them in chimeric embryos in vivo and in vitro.The engineered cells retained embryonic and extra-embryonic developmental potential.Meanwhile,we generated a chimeric monkey carrying bioluminescent cells,which were able to track chimeric cells for more than 2 years in living animals.Our study could have broad utility in primate stem cell engineering and in utilizing chimeric monkey models forclinical studies.

关键词： pluripotent stem cells bioluminescence imaging non-human primates

Multi-region calcium imaging in freely behaving mice with ultra-compact head-mounted fluorescence microscopes

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National science Review 2024年第1期11卷 161-173页

作者： Feng Xue Fei Li Ke-ming Zhang Lufeng Ding Yang Wang Xingtao Zhao Fang Xu Danke Zhang Mingzhai Sun Pak-Ming Lau Qingyuan Zhu Pengcheng Zhou Guo-Qiang Bi Institute of Artiflcial Intelligence Hefei Comprehensive National Science Center Department of Precision Machinery and Precision Instruments University of Science and Technology of China Hefei National Laboratory for Physical sciences at the Microscale University of Science and Technology of China Interdisciplinary Center for Brain Information the Brain Cognition and Brain Disease Institute Shenzhen Institute of Advanced Technology Chinese Academy of Sciences faculty of life and Health sciences Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences School of life sciences University of Science and Technology of China Institute of Semiconductors Chinese Academy of Sciences Department of Modern life sciences and Biotecnology Xiongan Institute of Innovation Xiongan New Area Shenzhen-Hong Kong Institute of Brain science-Shenzhen Fundamental Research Institutions Suzhou Institute for Advanced Research University of Science and Technology of China

To investigate the circuit-level neural mechanisms of behavior, simultaneous imaging of neuronal activity in multiple cortical and subcortical regions is highly desired. Miniature head-mounted microscopes offer the capability of calcium imaging in freely behaving animals. However, implanting multiple microscopes on a mouse brain remains challenging due to space constraints and the cumbersome weight of the equipment.Here, we present TINIscope, a Tightly Integrated Neuronal Imaging microscope optimized for electronic and opto-mechanical design. With its compact and lightweight design of 0.43 g, TINIscope enables unprecedented simultaneous imaging of behavior-relevant activity in up to four brain regions in mice.Proof-of-concept experiments with TINIscope recorded over 1000 neurons in four hippocampal subregions and revealed concurrent activity patterns spanning across these regions. Moreover, we explored potential multi-modal experimental designs by integrating additional modules for optogenetics, electrical stimulation or local field potential recordings. Overall, TINIscope represents a timely and indispensable tool for studying the brain-wide interregional coordination that underlies unrestrained behaviors.

关键词： miniature microscope multiple sites calcium imaging multimodal integration hippocampus

Symmetric Brownian motor subjected to Lévy noise

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Chinese Physics B 2024年第2期33卷 222-227页

作者：贾考胡兰聂林如 faculty of science Kunming University of Science and TechnologyKunming 650500China

In the past few years,attention has mainly been focused on the symmetric Brownian motor(BM)with Gaussian noises,whose current and energy conversion efficiency are very low.Here,we investigate the operating performance of the symmetric BM subjected to Lévy noise.Through numerical simulations,it is found that the operating performance of the motor can be greatly improved in asymmetric Lévy noise.Without any load,the Lévy noises with smaller stable indexes can let the motor give rise to a much greater current.With a load,the energy conversion efficiency of the motor can be enhanced by adjusting the stable indexes of the Lévy noises with symmetry breaking.The results of this research are of great significance for opening up BM’s intrinsic physical mechanism and promoting the development of nanotechnology.

关键词： symmetric Brownian motor average velocity energy conversion efficiency Lévy noise

A Nonparametric Model Checking Test for Functional Linear Composite Quantile Regression Models

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Journal of Systems science & Complexity 2024年第4期37卷 1714-1737页

作者： XIA Lili DU Jiang ZHANG Zhongzhan faculty of science Beijing University of Technology

This paper is focused on the goodness-of-fit test of the functional linear composite quantile regression model. A nonparametric test is proposed by using the orthogonality of the residual and its conditional expectation under the null model. The proposed test statistic has an asymptotic standard normal distribution under the null hypothesis, and tends to infinity in probability under the alternative hypothesis, which implies the consistency of the test. Furthermore, it is proved that the test statistic converges to a normal distribution with nonzero mean under a local alternative hypothesis. Extensive simulations are reported, and the results show that the proposed test has proper sizes and is sensitive to the considered model discrepancies. The proposed methods are also applied to two real datasets.

关键词： Composite quantile regression consistent test functional data nonparametric test quadratic form

Integration of multiple flexible electrodes for realtime detection of barrier formation with spatial resolution in a gut-on-chip system

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Microsystems & Nanoengineering 2024年第1期10卷 105-114页

作者： Mara Lucchetti Gabriel Werr Sofia Johansson Laurent Barbe Léa Grandmougin Paul Wilmes Maria Tenje Luxembourg Centre for Systems Biomedicine(LCSB) University of LuxembourgEsch-sur-Alzette L-4362Luxembourg Division of Biomedical Engineering Department of Materials Science and EngineeringScience for Life LaboratoryUppsala University75121 UppsalaSweden Department of life sciences and Medicine Faculty of ScienceTechnology and MedicineUniversity of LuxembourgEsch-sur-Alzette L-4362Luxembourg

In healthy individuals,the intestinal epithelium forms a tight barrier to prevent gut bacteria from reaching blood circulation.To study the effect of probiotics,dietary compounds and drugs on gut barrier formation and disruption,human gut epithelial and bacterial cells can be cocultured in an in vitro model called the human microbial crosstalk(HuMiX)gut-on-a-chip system.Here,we present the design,fabrication and integration of thin-film electrodes into the HuMiX platform to measure transepithelial electrical resistance(TEER)as a direct readout on barrier tightness in realtime.As various aspects of the HuMiX platform have already been set in their design,such as multiple compressible layers,uneven surfaces and nontransparent materials,a novel fabrication method was developed whereby thin-film metal electrodes were first deposited on flexible substrates and sequentially integrated with the HuMiX system via a transfer-tape approach.Moreover,to measure localized TEER along the cell culture chamber,we integrated multiple electrodes that were connected to an impedance analyzer via a multiplexer.We further developed a dynamic normalization method because the active measurement area depends on the measured TEER levels.The fabrication process and system setup can be applicable to other barrier-on-chip systems.As a proof-of-concept,we measured the barrier formation of a cancerous Caco-2 cell line in real-time,which was mapped at four spatially separated positions along the HuMiX culture area.

关键词： barrier system multiple

Ultrafast laser-chemical modification hybrid fabrication of hydrostatic bearings with a superhydrophobicity solid-liquid interface

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science China(Technological sciences) 2024年第3期67卷 696-708页

作者： GUO MingHui RONG YouMin HUANG Yu FENG XiaoLin HU HaiDong WU CongYi ZHANG GuoJun State Key Laboratory of Intelligent Manufacturing Equipment and technology Huazhong University of Science and Technology Wuhan 430074China School of Mechanical science and Engineering Huazhong University of Science and TechnologyWuhan 430074China faculty of Engineering and life sciences Universiti Selangor Bestari JayaSelangor 45600Malaysia

Oil film vortex severely reduces the stability of hydrostatic bearings. A solid-liquid interface with drag and slip properties can weaken the oil film vortex of the bearing. Here, a combined picosecond laser ablation and chemical modification method is proposed to prepare surfaces with microbulge array structure on 6061 aluminum alloy substrates. Because of the low surface energy of the perfluorododecyltriethoxysilane modification and the bulge geometry of the microbulge array structure, the surface shows excellent superhydrophobicity. The optimum contact angle in air for water is 164°, and that for oil is 139°. Two surfaces with “lotus-leaf effect” and “rose-petal effect” were obtained by controlling the processing parameters. The drag reduction properties of superhydrophobic surfaces were systematically investigated with slip lengths of 22.26 and 36.25 μm for deionized water and VG5 lubricant, respectively. In addition, the superhydrophobic surface exhibits excellent mechanical durability and thermal stability. The proposed method provides a new idea for vortex suppression in hydrostatic bearings and improves the stability of bearings in high-speed operation.

关键词： superhydrophobicity surface ultrafast laser drag reduction solid-liquid interface microbulge array structure

A practical guide for fast implementation of SNARE-mediated liposome fusion

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Biophysics Reports 2024年第1期10卷 31-40页

作者： Shen Wang Cong Ma Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and TechnologyHuazhong University of Science and Technology

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor(SNAER) family proteins are the engines of most intra-cellular and exocytotic membrane fusion pathways(Jahn and Scheller 2006).Over the past two decades, in-vitro liposome fusion has been proven to be a powerful tool to reconstruct physiological SNARE-mediated membrane fusion processes(Liu et al. 2017). The reconstitution of the membrane fusion process not only provides direct evidence of the capability of the cognate SNARE complex in driving membrane fusion but also allows researchers to study the functional mechanisms of regulatory proteins in related pathways(Wickner and Rizo 2017). Heretofore, a variety of delicate methods for in-vitro SNARE-mediated liposome fusion have been established(Bao et al. 2018;Diao et al. 2012; Duzgunes 2003; Gong et al. 2015; Heo et al. 2021; Kiessling et al. 2015; Kreye et al.2008; Kyoung et al. 2013; Liu et al. 2017; Scott et al. 2003). Although technological advances have made reconstitution more physiologically relevant, increasingly elaborate experimental procedures, instruments, and data processing algorithms nevertheless hinder the non-experts from setting up basic SNARE-mediated liposome fusion assays. Here, we describe a low-cost, timesaving, and easy-to-handle protocol to set up a foundational in-vitro SNARE-mediated liposome fusion assay based on our previous publications(Liu et al. 2023; Wang and Ma 2022). The protocol can be readily adapted to assess various types of SNARE-mediated membrane fusion and the actions of fusion regulators by using appropriate alternative additives(e.g., proteins, macromolecules, chemicals, etc.). The total time required for one round of the assay is typically two days and could be extremely compressed into one day.

关键词： Liposome fusion SNARE In-vitro reconstitution Protocol

Determining an optimal control strategy for anthropogenic VOC emissions in China based on source emissions and reactivity

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Journal of Environmental sciences 2024年第2期136卷 248-260页

作者： Ruipeng Wang Xiaoqi Wang Shuiyuan Cheng Jiaxian Zhu Xinyu Zhang Long Cheng Kai Wang Key Laboratory of Beijing on Regional Air Pollution Control Faculty of Environment and LifeBeijing University of TechnologyBeijing 100124China

An evidence-based control strategy for emission reduction of VOC sources can effectively solve the regional PM2.5and O3compound pollution in China.We estimated the anthropogenic VOC emission inventory in China in 2018 and established a source profile database containing 129 sources based on localized detection and the latest research results.Then,the distribution of the ozone formation potential(OFP)and secondary organic aerosol formation potential(SOAFP)for emission sources was analyzed.Moreover,priority control routes for VOC emission sources were proposed for different periods.Anthropogenic VOC emissions in China reached 27,211.8 Gg in 2018,and small passenger cars,industrial protective coatings,biomass burning,heavy trucks,printing,asphalt paving,oil storage and transportation,coking,and oil refining were the main contributors.Industrial protective coatings,small passenger cars,and biomass burning all contributed significantly to OFP and SOAFP.Priority in emission reduction control should be given to industrial protective coatings,small passenger cars,heavy trucks,coking,printing,asphalt paving,chemical fibers,and basic organic chemical sources over the medium and long term in China.In addition,the priority control route for VOC emission sources should be adjusted according to the variations in VOC emission characteristics and regional differences,so as to obtain the maximum environmental benefits.

关键词： Volatile organic compounds Anthropogenic emission inventory Reactivity Emission projection Priority control route

The role of a novel antibacterial substance,cyclic opine-producing Lacticaseibacillus rhamnosus LS8 in ameliorating ulcerative colitis:a fecal microbiota transplantation study

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Food science and Human Wellness 2024年第2期13卷 778-790页

作者： Tao Wang Shuang Wang Shuchen Dong Ruiling Wang Shuxuan Wang Jie Yang Xin Wang Xin Lü College of Food science and Engineering Northwest Agriculture and Forestry UniversityYangling 712100China faculty of Food science and Engineering Kunming University of Science and TechnologyKunming 650500China School of life science and technology Xinjiang UniversityUrumqi 830046China

Intestinal microbiota imbalance may worsen the progression of ulcerative colitis(UC).Lacticaseibacillus rhamnosus LS8(LR)has the potential ability to regulate microbiota through producing a novel antibacterial substance,cyclic opine:cycloalanopine.This study aimed to investigate whether LR could ameliorate dextran sulfate sodium-induced UC in mice via modulating intestinal microbiota using fecal microbiota transplantation(FMT)experiment.The results showed that both LR and FMT attenuated UC as evidenced by 1)alleviating disease activity index and colonic pathology;2)up-regulating MUCs and tight junction proteins;3)increasing oxidative mediators and decreasing antioxidant mediators;4)down-regulating proinflammatory cytokines and chemokines.These results were mainly attributable to the microbiota-regulating effect of LR,including increasing beneficial bacteria(like Akkermansia)and its related SCFAs,while decreasing harmful bacteria(like Proteobacteria)and its related LPS,thereby suppressing the hyperactivation of TLR4/NF-κB pathway.Consequently,LR can alleviate UC and is a potential dietary supplement to attenuate UC.

关键词： Gut barrier Gut microbiota Fecal microbiota transplantation Lacticaseibacillus rhamnosus Oxidative stress Ulcerative colitis