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Neural Regeneration Research 2024年第5期19卷 1150-1155页

作者： Shuanglong Yi Linfang Wang Margaret S.Ho Shiping Zhang School of life science and Technology ShanghaiTech UniversityShanghaiChina College of life sciences University of Chinese Academy of SciencesBeijingChina

Parkinson’s disease is a progressive neurodegenerative disease characterized by motor deficits,dopaminergic neuron loss,and brain accumulation ofα-synuclein aggregates called Lewy bodies.Dysfunction in protein degradation pathways,such as autophagy,has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson’s disease.However,it is less well understood how protein aggregates are eliminated in glia,the other cell type in the brain.In the present study,we show that autophagy-related gene 9(Atg9),the only transmembrane protein in the autophagy machinery,is highly expressed in Drosophila glia from adult brain.Results from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network,autophagosomes,and lysosomes in glia.Atg9 is persistently in contact with these organelles.Lacking glial atg9 reduces the number of omegasomes and autophagosomes,and impairs autophagic substrate degradation.This suggests that glial Atg9 participates in the early steps of autophagy,and hence the control of autophagic degradation.Importantly,loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons,locomotion deficits,and glial activation.Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson’s disease.These results may provide new insights on the underlying mechanism of Parkinson’s disease.

关键词： Atg9 autophagy glia Parkinson’s disease

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Deciphering and integrating invariants for neural operator learning with various physical mechanisms

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National science Review 2024年第4期11卷 111-122页

作者： Rui Zhang Qi Meng Zhi-Ming Ma academy of Mathematics and Systems science Chinese Academy of Sciences(CAS) Microsoft Research

Neural operators have been explored as surrogate models for simulating physical systems to overcome the limitations of traditional partial differential equation(PDE) solvers. However, most existing operator learning methods assume that the data originate from a single physical mechanism, limiting their applicability and performance in more realistic scenarios. To this end, we propose the physical invariant attention neural operator(PIANO) to decipher and integrate the physical invariants for operator learning from the PDE series with various physical mechanisms. PIANO employs self-supervised learning to extract physical knowledge and attention mechanisms to integrate them into dynamic convolutional layers.Compared to existing techniques, PIANO can reduce the relative error by 13.6%–82.2% on PDE forecasting tasks across varying coefficients, forces or boundary conditions. Additionally, varied downstream tasks reveal that the PI embeddings deciphered by PIANO align well with the underlying invariants in the PDE systems, verifying the physical significance of PIANO.

关键词： neural operator PDE solver contrastive learning physical invariants

Regulation of insect behavior by non-coding RNAs

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science China(life sciences) 2024年第6期67卷 1106-1118页

作者： Jing He Le Kang State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100101China Beijing Institutes of life sciences Chinese Academy of SciencesBeijing 100101China College of life science Hebei UniversityBaoding 071002China

The adaptation of insects to environments relies on a sophisticated set of behaviors controlled by molecular and physiological processes.Over the past several decades,accumulating studies have unveiled the roles of non-coding RNAs(nc RNAs)in regulating insect behaviors.nc RNAs assume particularly pivotal roles in the behavioral plasticity of insects by rapidly responding to environmental stimuli.nc RNAs also contribute to the maintenance of homeostasis of insects by fine-tuning the expression of target genes.However,a comprehensive review of nc RNAs'roles in regulating insect behaviors has yet to be conducted.Here,we present the recent progress in our understanding of how nc RNAs regulate various insect behaviors,including flight and movement,social behavior,reproduction,learning and memory,and feeding.We refine the intricate mechanisms by which nc RNAs modulate the function of neural,motor,reproductive,and other physiological systems,as well as gene expression in insects like fruit flies,social insects,locusts,and mosquitos.Furthermore,we discuss potential avenues for future studies in nc RNA-mediated insect behaviors.

关键词： ncRNAs insect behavior plasticity fine-tuning environmental adaptation

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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

Avian lower beak is always overlooked:its coordinate role in shaping species-specific beak should not be underestimated

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Integrative Zoology 2024年第2期19卷 339-342页

作者： Yalin CHENG Fumin LEI College of life science/Hebei Basic science Center for Biotic Interactions Institute of Life Science and Green DevelopmentHebei UniversityBaodingChina Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of SciencesBeijingChina University of Chinese academy of sciences BeijingChina Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingChina

The beak is a key evolutionary innovation in the avian tree of life.Its diversity in morphology shows birds’successful colonization of various ecological niches on the Earth(Pigot et al.2020),and its morphological plasticity can also enable birds to rapidly respond to changes in environments(Grant&Grant 2006).These natures helped birds survive multiple extinction events(Larson et al.2016).Therefore,investigating the morphological evolution of avian beaks and the underlying developmental and molecular mechanisms will help to decipher the evolution of birds and boost the development of the theory of evolutionary biology.

关键词： coordinate extinction enable

A Brief Overview of the Development and Significance of Modern Scientific Medicine in China:Take Chinese academy of Medical science and Peking Union Medical College as an Example

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Chinese Medical sciences Journal 2024年第2期39卷 140-143页

作者： Pu-An Cui Zhe-Xi Gong Zhong He School of Humanities and Social sciences Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China

Since the early 20th century,China has gradually established a clinical,educational,and research system centered around modern scientific medicine,which has now become the dominant force in China's medical and health system and services,with the construction and development of the Chinese academy of Medical sciences and Peking Union Medical College as the most prominent symbol.The scientific medicine in the new era requires close cooperation across multiple disciplines and fields to build a high-quality and efficient medical and health service system.It also involves combining the excellent traditional Chinese culture with Western medicine to explore a unique path of modern scientific medicine with Chinese characteristics.

关键词： modern scientific medicine cultural confidence multiple view

Understanding the rapid spread of antimicrobial resistance genes mediated by Is26

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mlife 2024年第1期3卷 101-109页

作者： Na Tang Dawei Wei Yuan Zeng Gang Zhang Chao Wang Jie Feng Yuqin Song State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBejingChina College of life science University of Chinese Academy of SciencesBeijingChina

Insertion sequences(ISs)promote the transmission of antimicrobial resistance genes(ARGs)across bacterial populations.However,their contributions and dynamics during the transmission of resistance remain unclear.In this study,we selected is26 as a representative transposable element to decipher the relationship between ISs and ARGs and to investigate their transfer features and transmission trends.We retrieved 2656 translocatable IS26-bounded units with ARGs(tiS26-bUs-ARGs)in complete bacterial genomes from the NCBI RefSeq database.In total,124 ARGs spanning 12 classes of antibiotics were detected,and the average contribution rate of IS26 to these genes was 41.2%.We found that IS26-bounded units(IS26-bUs)mediated extensive ARG dissemination within the bacteria of the Gammaproteobacteria class,showing strong transfer po-tential between strains,species,and even phyla.The Is26-bUs expanded in bacterial populations over time,and their temporal expansion trend was significantly correlated with antibiotic usage.This wide dissemination could be due to the nonspecific target site preference of is26.Finally,we experimentally confirmed that the introduction of a single copy of is26 could lead to the formation of a composite transposon mediating the transmission of“passenger”genes.These observations extend our knowledge of the Is26 and provide new insights into the mediating role of ISs in the dissemination of antibiotic resistance.

关键词： antibiotic consumption antibiotic resistance genes horizontal gene transfer insertion sequence Is26

Synthesis and anti-HIV activities of phorbol derivatives

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Chinese Journal of Natural Medicines 2024年第2期22卷 146-160页

作者： HUANG Xiaolei TANG Chengrun HUANG Xusheng YANG Yun LI Qirun MA Mengdi ZHAO Lei YANG Liumeng CUI Yadong ZHANG Zhenqing ZHENG Yongtang ZHANG Jian College of Pharmaceutical science Soochow UniversitySuzhou 215123China Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese academy of sciences/Key Laboratory of Bioactive Peptides of Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Kunming College of life science University of Chinese Academy of SciencesKunmingYunnan 650204China

In this study,37 derivatives of phorbol esters were synthesized and their anti-HIV-1 activities evaluated,building upon our previous synthesis of 51 phorbol derivatives.12-Para-electron-acceptor-trans-cinnamoyl-13-decanoyl phorbol derivatives stood out,demonstrating remarkable anti-HIV-1 activities and inhibitory effects on syncytia formation.These derivatives exhibited a higher safety index compared with the positive control drug.Among them,12-(trans-4-fluorocinnamoyl)-13-decanoyl phorbol,designated as compound 3c,exhibited the most potent anti-HIV-1 activity(EC_(50)2.9 nmol·L^(−1),CC50/EC_(50)11117.24)and significantly inhibited the formation of syncytium(EC_(50)7.0 nmol·L^(−1),CC50/EC_(50)4891.43).Moreover,compound 3c is hypothesized to act both as an HIV-1 entry inhibitor and as an HIV-1 reverse transcriptase inhibitor.Isothermal titration calorimetry and molecular docking studies indicated that compound 3c may also function as a natural activator of protein kinase C(PKC).Therefore,compound 3c emerges as a potential candidate for developing new anti-HIV drugs.

关键词： Phorbol esters Anti-HIV-1 activity Syncytia formation 12-(Trans-4-fluorocinnamoyl)-13-decanoyl phorbol Safety index HIV-1 entry inhibitor HIV-1 reverse transcriptase inhibitor PKC activator

Solid-state atomic hydrogen as a broad-spectrum RONS scavenger for accelerated diabetic wound healing

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National science Review 2024年第2期11卷 196-206页

作者： Man Luo Qin Wang Gang Zhao Wei Jiang Cici Zeng Qingao Zhang Ruyu Yang Wang Dong Yunxi Zhao Guozhen Zhang Jun Jiang Yucai Wang Qing Zhu Key Laboratory of Precision and Intelligent Chemistry School of Chemistry and Materials Science University of Science and Technology of China Department of Radiology The First Affiliated Hospital of University of Science and Technology of China Division of Life Sciences and Medicine University of Science and Technology of China Shenzhen Senior High School Institute of Intelligent Innovation Henan Academy of Sciences

Hydrogen therapy shows great promise as a versatile treatment method for diseases associated with the overexpression of reactive oxygen and nitrogen species（RONS）. However, developing an advanced hydrogen therapy platform that integrates controllable hydrogen release, efficient RONS elimination, and biodegradability remains a giant technical challenge. In this study, we demonstrate for the first time that the tungsten bronze phase H0.53WO3（HWO） is an exceptionally ideal hydrogen carrier, with salient features including temperature-dependent highly-reductive atomic hydrogen release and broad-spectrum RONS scavenging capability distinct from that of molecular hydrogen. Moreover, its unique p H-responsive biodegradability ensures post-therapeutic clearance at pathological sites. Treatment with HWO of diabetic wounds in an animal model indicates that the solid-state atomic H promotes vascular formation by activating M2-type macrophage polarization and anti-inflammatory cytokine production, resulting in acceleration of chronic wound healing. Our findings significantly expand the basic categories of hydrogen therapeutic materials and pave the way for investigating more physical forms of hydrogen species as efficient RONS scavengers for clinical disease treatment.

关键词： atomic hydrogen RONS scavenger inflammatory regulation diabetic wound healing hydrogen therapy

Effects of simulated gut pH environment on bacterial composition and pheromone production of Dendroctonus valens

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Insect science 2024年第1期31卷 225-235页

作者： Qingjie Cao Yu Zhao Tuuli-Marjaana Koski Huiping Li Jianghua Sun College of Forestry Hebei Agricultural UniversityBaodingHebei ProvinceChina State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijingChina College of life science/Hebei Basic science Center for Biotic Interactions Institute of Life Science and Green DevelopmentHebei UniversityBaodingHebei ProvinceChina

Bark beetles are an economically and ecologically important insect group,with aggregation behavior and thus host colonization success depends on pheromone-mediated communication.For some species,such as the major invasive forest pest in China,red turpentine beetle(Dendroctonus valens),gut microbiota participates in pheromone production by converting tree monoterpenes into pheromone products.However,how variation in gut microenvironment,such as pH,affects the gut microbial composition,and consequently pheromone production,is unknown.In this study,we fed wild caught D.valens with 3 different pH media(main host diet with natural pH of 4.7;a mildly acidic diet with pH 6 mimicking the beetle gut pH;and highly acidic diet with pH 4),and measured their effects on the gut pH,bacterial community and production of the main aggregation and anti-aggregation pheromone(verbenone).We further tested the verbenone production capacity of 2 gut bacterial isolates in different pH environments(pH 6 and 4).Compared to natural state or main host diet,feeding on less acidic diet(pH 6)diluted the acidity of the gut,whereas feeding on highly acidic diet(pH 4)enhanced it.Both changes in gut pH reduced the abundance of dominant bacterial genera,resulting in decreased verbenone production.Similarly,the highest pheromone conversion rate of the bacterial isolates was observed in pH mimicking the acidity in beetle gut.Taken together,these results indicate that changes in gut pH can affect gut microbiota composition and pheromone production,and may therefore have the potential to affect host colonization behavior.

关键词： Dendroctonus valens gut bacteria gut pH verbenone