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Brain circuits for retching-like behavior

National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic Medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State Key Laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science Laboratory National institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+*** Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

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Decoding bone-inspired and cell-instructive cues of scaffolds for bone tissue engineering

Engineered Regeneration

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Engineered Regeneration 2024年第1期5卷 21-44页

作者： Zahid Hussain Shah Mehmood Xingzhu Liu Yuanshan Liu Guocheng Wang Renjun Pei School of Nano-Tech and Nano-Bionics University of Science and Technology of China(USTC)Hefei 230026PR China CAS Key Laboratory for Nano-Bio Interface Suzhou Institute of Nano-Tech and Nano-Bionics(SINANO)Chinese Academy of SciencesSuzhou 215123PR China Research Center for human Tissues and Organs Degeneration Shenzhen Institute of Advanced Technology(SIAT)Chinese Academy of ScienceShenzhen 518055PR China

Bone fractures are common occurrence in clinical settings,creating a high demand for effective repair ***,limited graft availability,donor site morbidities,unpredictable clinical outcomes,immunologic reactions,infection risks,and geometrical mismatching concerns hampered tissue graft use and underscored the need for scaffolds for more effective bone reconstructions due to their tunable *** progress has been carried out in past decade in the fields of nanoceramics synthesis,bioconjugate chemistry,and composite material *** review outlines hierarchical structures and biology of bone tissue,materialistic compo-nents of scaffolds(bioceramics,polymers,bioactive drugs),featured scaffolding strategies(nanofibers,hydrogels,aerogels,bioprinting,and fiber-reinforced composite),and emphasis that hierarchical and physiochemical char-acteristics of bone should be used as an inspiration for scaffold *** review discussed how differences in materiobiological aspects of scaffolds,such as polymer/bioceramic nanocomposite,mineralized nanocomposite,matrix-rich nanocomposite,3D microenvironmental cues,pore space cues,mechanical cues,usage of physical stimulation(magnetic,electroactive,and photoactivated cues),surface cues(wettability,roughness,textured,and surface charge),and biointerface cues(cell-biomaterial interactions,cell-selective homing,and cell regula-tory strategies)modulate cellular and biological response for bone tissue *** study further outlines the challenges and benefits of integrating materiobiological cues of scaffolds for bone tissue engineering.

关键词： Bone substitute Scaffolds Mineralization Materiobiology Bone tissue engineering

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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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Ethical concerns in aging research: perspectives of global frontline researchers

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Science China Life Sciences 2024年第10期67卷 2149-2156页

作者： Yaojin Peng Lulu Ding Zhenyu Xiao Moshi Song Jianwei Lv Guang-Hui Liu Key Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of Sciences University of Chinese Academy of Sciences Beijing institute for Stem Cell and Regenerative Medicine institute for Stem Cell and Regeneration Chinese Academy of Sciences Aging Biomarker Consortium (ABC) School of Life Science Beijing Institute of Technology School of Life Sciences Xiamen University Advanced Innovation Center for human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical University Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical University

This study investigated the ethical landscape of aging research amid the increasing global focus on extending the human lifespan and health span. Our global survey of 180 researchers across 38 jurisdictions revealed divergent perceptions of aging, a consensus regarding the feasibility of delaying aging, and multiple perspectives regarding lifespan extension. The present findings underscore a paradigm shift toward inclusive and ethically sound research, emphasizing the need for an approach that strikes a balance between basic and clinical research. In addition, this study highlighted key ethical concerns in aging research, including the effects of misleading advertising, potential inequality in access to aging interventions, and risks pertaining to the extrapolation of research findings from lower-model organisms to humans. The insights presented in this paper call for an integrated approach for overcoming the complex ethical and societal challenges in aging research to ensure responsible and equitable advancements in this burgeoning field.

关键词： aging ethical landscape ethics surveys and questionnaires

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Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

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Neural Regeneration Research 2025年第4期20卷 1124-1134页

作者： Yanting Liu Wei Huang Jiayi Wen Xin Xiong Ting Xu Qi Wang Xiusheng Chen Xianxian Zhao Shihua Li Xiaojiang Li Weili Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong-Hongkong-Macao CNS Regeneration Institute of Jinan UniversityJinan UniversityGuangzhouGuangdong ProvinceChina

The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal ***,it remains largely unclear how PINK1 and Parkin are expressed in mammalian *** has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small *** this issue is critical for elucidating the in vivo roles of PINK1 and ***,we showed that the PINK1 kinase is selectively expressed as a truncated form(PINK1–55)in the primate *** the present study,we used multiple antibodies,including our recently developed monoclonal anti-PINK1,to validate the selective expression of PINK1 in the primate *** found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages,which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey ***1 was enriched in the membrane-bound fractionations,whereas Parkin was soluble with a distinguishable *** double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes,though they did colocalize on mitochondria when the cells were exposed to mitochondrial *** findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

关键词： neurodegeneration Parkin Parkinson’s disease PINK1 subcellular distribution

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Association of Serum Folate and Vitamin B_(12) Concentrations with Obesity in Chinese Children and Adolescents

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Biomedical and Environmental Sciences 2024年第3期37卷 242-253页

作者： ZHU Qian Rang KOK E Dieuwertje BEKELE Hailu Tesfaye MANUSAMA Koen ZHANG Jing Xian XIE Wei ZONG Wen Qi ZUO Hui ZHANG Jian KAMPMAN Ellen DAI Yue Jiangsu Provincial Center for Disease Control and Prevention Nanjing 210009JiangsuChina Division of human Nutrition and Health Wageningen University&ResearchWageningen 176700 AAThe Netherlands School of Public Health Medical College of Soochow UniversitySuzhou 215123JiangsuChina National institute for Nutrition and Health Chinese Center for Disease Control and PreventionBeijing 100050China

Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and *** A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,*** indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were *** linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of *** We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood *** and adolescents with high levels of vitamin B12 and folate were less likely to be obese.

关键词： Folate Vitamin B12 Childhood obesity Micronutrient

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High-resolution bone microstructure imaging based on ultrasonic frequency-domain full-waveform inversion

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Chinese Physics B 2021年第1期30卷 295-310页

作者： Yifang Li Qinzhen Shi Ying Li Xiaojun Song Chengcheng Liu Dean Ta Weiqi Wang Department of Electronic Engineering Fudan UniversityShanghaiChina human phenome institute Fudan UniversityShanghaiChina Academy for Engineering and Technology Fudan UniversityShanghaiChina

The main challenge in bone ultrasound imaging is the large acoustic impedance contrast and sound velocity differences between the bone and surrounding soft tissue. It is difficult for conventional pulse-echo modalities to give accurate ultrasound images for irregular bone boundaries and microstructures using uniform sound velocity assumption rather than getting a prior knowledge of sound speed. To overcome these limitations, this paper proposed a frequency-domain fullwaveform inversion(FDFWI) algorithm for bone quantitative imaging utilizing ultrasonic computed tomography(USCT).The forward model was calculated in the frequency domain by solving the full-wave equation. The inverse problem was solved iteratively from low to high discrete frequency components via minimizing a cost function between the modeled and measured data. A quasi-Newton method called the limited-memory Broyden–Fletcher–Goldfarb–Shanno algorithm(L-BFGS) was utilized in the optimization process. Then, bone images were obtained based on the estimation of the velocity and density. The performance of the proposed method was verified by numerical examples, from tubular bone phantom to single distal fibula model, and finally with a distal tibia-fibula pair model. Compared with the high-resolution peripheral quantitative computed tomography(HR-p QCT), the proposed FDFWI can also clearly and accurately presented the wavelength scaled pores and trabeculae in bone images. The results proved that the FDFWI is capable of reconstructing high-resolution ultrasound bone images with sub-millimeter resolution. The parametric bone images may have the potential for the diagnosis of bone disease.

关键词： quantitative imaging full-waveform inversion bone microstructure ultrasonic computed tomography high resolution

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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 *** derivatives exhibited a higher safety index compared with the positive control *** 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 *** 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

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Elaborations of the influencing factors on the formation of secondary inorganic aerosols in a heavily polluted urban area of China

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Journal of Environmental Sciences 2024年第4期138卷 406-417页

作者： Shuang Wang Qiyuan Wang Ting Zhang Suixin Liu Steven Sai Hang Ho Jie Tian Hui Su Yong Zhang Luyao Wang Tingting Wu Junji Cao School of human Settlements and Civil Engineering Xi’an Jiaotong UniversityXi’an 710049China Key Laboratory of Aerosol Chemistry and Physics State Key Laboratory of Loess and Quaternary GeologyInstitute of Earth EnvironmentChinese Academy of SciencesXi’an 710061China CAS Center for Excellence in Quaternary Science and Global Change Xi’an 710061China National Observation and Research Station of Regional Ecological Environment Change and Comprehensive Management in the Guanzhong Plain Xi’an 710061China Division of Atmospheric Sciences Desert Research InstituteRenoNevada89512United States Hong Kong Premium Services and Research Laboratory KowloonHong Kong SARChina Xi’an institute for Innovative Earth Environment Research Xi’an 710061China institute of Atmospheric Physics Chinese Academy of SciencesBeijing 100029China

In this study,online water-soluble inorganic ions were detected to deduce the formation mechanism of secondary inorganic aerosol in Xianyang,China during *** dominant inorganic ions of sulfate(SO_(4)^(2-)),nitrate(NO_(3)^(-)),and ammonium(NH_(4)^(+))(the sum of those is abbreviated as SNA)accounted for 17%,21%,and 12% of PM_(2.5)mass,*** the air quality deteriorated from excellent to poor grades,the precursor gas sulfur dioxide(SO_(2))of SO_(4)^(2-)increased and then decreased with a fluctuation,while nitrogen dioxide(NO_(2))and ammonia(NH_(3)),precursors of NO_(3)^(-)and NH_(4)^(+),and SNA show increasing *** factors including boundary layer height(BLH),temperature,and wind speed also show decline trends,except relative humidity(RH).Meanwhile,the secondary conversion ratio shows a remarkable increasing trend,indicating that there was a strong secondary *** the perspective of chemical mechanisms,RH is positively correlated with sulfur oxidation ratios(SOR),nitrogen oxidation ratios(NOR),and ammonia conversion ratios,representing that the increase of humidity could promote the generation of ***,SOR and NOR were also positively related to the *** the one hand,the low wind speed and BLH led to the accumulation of *** the other hand,the increases of RH and ammonia promoted more formations of SNA and PM_(2.5).The results advance our identification of the contributors to the haze episodes and assist to establish more efficient emission controls in Xianyang,in addition to other cities with similar emission and geographical characteristics.

关键词： Haze episodes Secondary inorganic aerosol Secondary conversion ratio Meteorological factors

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Neogene integrative stratigraphy,biotas,and paleogeographical evolution of the Qinghai-Tibetan Plateau and its surrounding areas

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Science China Earth Sciences 2024年第4期67卷 1326-1359页

作者： Tao DENG Xiaomin FANG Qiang LI Shiqi WANG Feixiang WU Sukuan HOU Jiao MA Qigao JIANGZUO Danhui SUN Yan ZHENG Qinqin SHI Boyang SUN Lu LI Key Laboratory of Vertebrate Evolution and human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China CAS Center for Excellence in Life and Paleoenvironment Beijing 100044China University of Chinese Academy of Sciences Beijing 100049China CAS Center for Excellence in Tibetan Plateau Earth Sciences and Key Laboratory of Continental Collision and Plateau Uplift Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China Key Laboratory of Orogenic Belts and Crustal Evolution School of Earth and Space SciencesPeking UniversityBeijing 100871China

The remarkable uplift of the Tibetan Plateau in the Neogene had great impacts on the climate and environment of East Asia and even the ***,establishment of the Neogene stratigraphic framework of the Tibetan Plateau is of great significance to research in various fields of *** on marine sediments,the international chronostratigraphic system of the Neogene is divided into six stages in the Miocene and two stages in the *** the beginning of the Cenozoic,the share of terrestrial strata on continents has increased *** the Neogene,it had far exceeded that of marine strata,and almost all deposits on the Tibetan Plateau and its surrounding areas were terrestrial *** China,the Miocene includes five stages and the Pliocene includes two *** for the Tunggurian of the Miocene,which has a lower boundary at 15 Ma,the other stages have the same paleomagnetic definitions and time intervals as the corresponding international marine *** fossils play a very important role in the division and correlation of Cenozoic terrestrial strata,and rodent,carnivore,proboscidean,perissodactyl and artiodactyl fossils are especially important in Neogene terrestrial *** are many basins with well-exposed strata and abundant mammalian fossils in the Tibetan *** lower boundary stratotype sections of the Neogene Xiejian and Bahean stages are located respectively in the Xining and Linxia basins,and there are precise paleomagnetic dates in coordination with mammalian *** lower boundary stratotypes of other stages can also be effectively determined in the Tibetan *** first appearing mammalian genera in East Asia also appeared in the Tibetan Plateau and its surrounding areas,especially in the Linxia Basin on the northeast margin and in the Siwaliks on the southwest *** them,Prodeinotherium first appeared at the bottom of the Miocene in the Siwaliks,and the earliest Hipparion of the Old

关键词： Tibetan Plateau Neogene Terrestrial stratum Mammalian fossil Paleomagnetism

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