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The key role of myostatin b in somatic growth in fishes derived from distant hybridization

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Science China(Life Sciences) 2024年第7期67卷 1441-1454页

作者： Qingfeng liu Lujiao Duan Bei Li Xuanyi Zhang Fanglei liu Jianming Yu Yuqin shu Fangzhou Hu Jingjing Lin Xiaoxia Xiong Shaojun liu State Key Laboratory of Developmental Biology of Freshwater Fish Hunan Normal UniversityChangsha 410081China College of Life Sciences Hunan Normal UniversityChangsha 410081China

The basic mechanism of heterosis has not been systematically and completely characterized.In previous studies,we obtained three economically important fishes that exhibit rapid growth,WR(WCC♀×RCC♂),WR-Ⅱ(WR♀×WCC♂),and WR-Ⅲ(WR-Ⅱ♀×4nAU♂),through distant hybridization.However,the mechanism underlying this rapid growth remains unclear.In this study,we found that WR,WR-Ⅱ,and WR-Ⅲshowed muscle hypertrophy and higher muscle protein and fat contents compared with their parent species(RCC and WCC).Candidate genes responsible for this rapid growth were then obtained through an analysis of 12 muscle transcriptomes.Notably,the mRNA level of mstnb(myostatin b),which is a negative regulator of myogenesis,was significantly reduced in WR,WR-Ⅱ,and WR-Ⅲcompared with the parent species.To verify the function of mstnb,a mstnb-deficient mutant RCC line was generated using the CRISPR-Cas9 technique.The average body weight of mstnb-deficient RCC at 12 months of age was significantly increased by 29.57%compared with that in wild-type siblings.Moreover,the area and number of muscle fibers were significantly increased in mstnb-deficient RCC,indicating hypertrophy and hyperplasia.Furthermore,the muscle protein and fat contents were significantly increased in mstnb-deficient RCC.The molecular regulatory mechanism of mstnb was then revealed by transcription profiling,which showed that genes related to myogenesis(myod,myog,and myf5),protein synthesis(PI3K-AKT-mTOR),and lipogenesis(pparγand fabp3)were highly activated in hybrid fishes and mstnb-deficient RCC.This study revealed that low expression or deficiency of mstnb regulates somatic growth by promoting myogenesis,protein synthesis,and lipogenesis in hybrid fishes and mstnb-deficient RCC,which provides evidence for the molecular mechanism of heterosis via distant hybridization.

关键词： distant hybridization heterosis somatic growth myostatin b genome editing

The identification of AMZ2 as a candidate causative gene in a severe teratozoospermia patient characterized by vacuolated spermatozoa

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Asian Journal of Andrology 2024年第1期26卷 107-111页

作者： liu liu Jing Yang Wen-Jing Zhang Yi-Ling Zhou Gui-Jun Zhao Ya huang shu-Yan Tang Obstetrics and Gynecology Hospital Fudan UniversityShanghai 200011China Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai 200011China State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development Department of Computational BiologySchool of Life SciencesFudan UniversityShanghai 200436China Shanghai Towako Hospital Shanghai 200131China Shanghai Institute of Medical Genetics Shanghai Children's HospitalShanghai Jiao Tong UniversityShanghai 200040China

Teratozoospermia with cephalic defects is one of the most severe types of sperm defects known to date.While several monogenic factors are linked to cephalic abnormalities,such as globozoospermia and macrozoospermia,the genetic cause of vacuolated spermatozoa remains inadequately described.Here,we analyzed whole-exome sequencing(WES)data for an individual from a consanguineous family with severely vacuolated spermatozoa.The analysis revealed a novel homozygous c.520A>G(p.Thr174Ala)variant in the archaelysin family metallopeptidase 2(AMZ2),a gene that encodes a zinc metalloprotease previously shown to be highly expressed in the testes and sperm.Multiple algorithms predicted this variant to be a damaging mutation.Consistent with an autosomal recessive mode of inheritance,this variant was inherited from heterozygous parental carriers.To investigate the potential pathogenicity of the identified variant,we compared the AMZ2 expression in sperm cells from the patient with the AMZ2 variant and from a healthy control.Immunoblot analysis revealed that the homozygous missense variant in AMZ2 abolished AMZ2 expression in the spermatozoa.Our findings reveal a candidate causative gene for vacuolated spermatozoa.

关键词： AMZ2 male infertility sperm quality teratozoospermia

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1690-1704页

作者： shu-Chang Nie Yan-hua Jing Lu Lu Si-Si Ren Guang Ji Han-Chen Xu Institute of Digestive Diseases Longhua HospitalChina-Canada Center of Research for Digestive DiseasesShanghai University of Traditional Chinese MedicineShanghai 200032China Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation Shanghai 200032China State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine(Shanghai University of Traditional Chinese Medicine) Shanghai 200032China

Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of CRC.MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer cells.Thus,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity.In this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC treatment.This study provides ideas and methods to enhance survival rates in patients with CRC.

关键词： Myeloid-derived suppressor cells Tumor microenvironment Colorectal cancer Therapy Immunosuppression

Oxidative cyclization of allyl compounds and isocyanide: A facile entry to polysubstituted 2-cyanopyrroles

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Chinese Chemical Letters 2024年第4期35卷 330-335页

作者： Yaping Zhang Wei Zhou Mingchun Gao Tianqi liu Bingxin liu Chang-hua Ding Bin Xu Department of Chemistry Affiliated Nantong Hospital of Shanghai University(The Sixth People's Hospital of Nantong)Shanghai Engineering Research Center of Organ RepairInnovative Drug Research CenterSchool of MedicineShanghai UniversityShanghai 200444China State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China

A facile Tf OH-catalyzed oxidative cyclization of allyl compounds and isocyanide has been developed with the assistance of DDQ, where isocyanide is used as the crucial "N" and "CN" sources. Highly functionalized 2-cyanopyrroles are constructed efficiently through a new formal [3 + 2] mode, demonstrating diverse reactivity and synthetic utility in organic chemistry. 2-Cyanopyrrole is converted into a nucleobase analogue of Remdesivir and 5H-pyrrolo[2,1-a]isoindole through a three-step or a two-step sequence, respectively. This protocol features broad substrate scope, operational simplicity and good functional group tolerance.

关键词： Isocyanide Cyanopyrrole Insertion Allyl compound Bronsted acid catalysis

MAX-DOAS and in-situ measurements of aerosols and trace gases over Dongying,China:Insight into ozone formation sensitivity based on secondary HCHO

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Journal of Environmental Sciences 2024年第1期135卷 656-668页

作者： Xiaojun Zheng Zeeshan Javed Cheng liu Aimon Tanvir Osama Sandhu Haoran liu Xiangguang Ji Chengzhi Xing hua Lin Daolin Du Institute of Environment and Ecology School of the Environment and Safety EngineeringJiangsu UniversityZhenjiang 212013China Department of Precision Machinery and Precision Instrumentation University of Science and Technology of ChinaHefei 230026China Key Laboratory of Environmental Optics&Technology Anhui Institute of Optics and Fine MechanicsHefei Institutes of Physical ScienceChinese Academy of SciencesHefei 230031China Center for Excellence in Regional Atmospheric Environment Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes University of Science and Technology of ChinaHefei 230026China Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention(LAP3) Department of Environmental Science and EngineeringFudan UniversityShanghai 200433China National Agromet Center Pakistan Meteorological DepartmentIslamabad 44000Pakistan Institute of Physical Science and Information Technology Anhui UniversityHefei 230601China Information Materials and Intelligent Sensing Laboratory of Anhui Province Anhui UniversityHefei 230601China School of Environmental Science and Optoelectronic Technology University of Science and Technology of ChinaHefei 230026China

This study presents a comprehensive overview of the atmospheric pollutants including Sulfur dioxide(SO_(2)),Nitrogen dioxide(NO_(2)),Formaldehyde(HCHO),Particulate Matter PM;PM_(10):diameter≤10μm,and PM_(2.5):diameter≤2.5μm,and Ozone(O_(3)),over Dongying(Shandong Province)from March-April 2018 and September-October 2019 by employing ground-based Multiple Axis Differential Optical Absorption Spectroscopy(MAX-DOAS)observations along with the in-situ measurements attained by the national air quality monitoring platform.The concentrations of SO_(2)and NO_(2)were under the acceptable level,while both PM_(2.5),and PM_(10)were higher than the safe levels as prescribed by national and international air quality standards.The results depict that 21%of the total observation days were found to be complex polluted days(PM_(2.5)>35μg/m^(3) and O_(3)>160μg/m^(3)).The secondary HCHO was used for accurate analysis of O_(3)sensitivity.A difference of 11.40%and 10%during March-April 2018 and September-October 2019 respectively in O_(3)sensitivity was found between HCHO_(total)/NO_(2)and HCHO_(sec)/NO_(2).The results indicate that primary HCHO have significant contribution in HCHO.O_(3)formation predominantly remained to be in VOC-limited and transitional regime during March-April 2018 and September-October 2019 in Dongying.These results imply that concurrent control of both NO_(x) and VOCs would benefit in ozone reductions.Additionally,the criteria pollutants(PM,SO_(2),and NO_(2))depicted strong correlations with each other except for O_(3)for which weak correlation coefficient was obtained with all the species.This study will prove to be baseline for designing of air pollution control strategies.

关键词： MAX-DOAS Trace gases Ozone sensitivity Secondary HCHO Complex Pollution

Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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Chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： liu Su-su YU Tong QIAO Yan-fang GU shu-xiao CHAI Xin-lou School of Traditional Chinese Medicine Beijing University of Chinese Medicine

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol(LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor(LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9(PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

Multisensory Conflict Impairs Cortico-Muscular Network Connectivity and Postural Stability: Insights from Partial Directed Coherence Analysis

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Neuroscience Bulletin 2024年第1期40卷 79-89页

作者： Guozheng Wang Yi Yang Kangli Dong Anke hua Jian Wang Jun liu Key Laboratory for Biomedical Engineering of Ministry of Education College of Biomedical Engineering&Instrument ScienceZhejiang UniversityHangzhou 310058China Taizhou Key Laboratory of Medical Devices and Advanced Materials Research Institute of Zhejiang University-TaizhouTaizhou 318000China Department of Sports Science College of EducationZhejiang UniversityHangzhou 310058China Center for Psychological Science Zhejiang UniversityHangzhou 310058China

Sensory conflict impacts postural control,yet its effect on cortico-muscular interaction remains underexplored.We aimed to investigate sensory conflict's influence on the cortico-muscular network and postural stability.We used a rotating platform and virtual reality to present subjects with congruent and incongruent sensory input,recorded EEG(electroencephalogram)and EMG(electromyogram)data,and constructed a directed connectivity network.The results suggest that,compared to sensory congruence,during sensory conflict:(1)connectivity among the sensorimotor,visual,and posterior parietal cortex generally decreases,(2)cortical control over the muscles is weakened,(3)feedback from muscles to the cortex is strengthened,and(4)the range of body sway increases and its complexity decreases.These results underline the intricate effects of sensory conflict on cortico-muscular networks.During the sensory conflict,the brain adaptively decreases the integration of conflicting information.Without this integrated information,cortical control over muscles may be lessened,whereas the muscle feedback may be enhanced in compensation.

关键词： Cortico-muscular interaction Postural control Virtual reality Electroencephalogram Electromyography Sensory integration

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

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Biomedical and Environmental Sciences 2024年第1期37卷 71-84页

作者： YANG Le Mei ZHENG Qi liu Xiao Jia LI Xian Xian Veronica Lim CHEN Qi ZHAO Zhong hua WANG shu Yang Department of Pathology School of Basic MedicineFudan UniversityShanghai 200032China Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedin 9054New Zealand Department of Pathology Huashan HospitalFudan UniversityShanghai 200040China Shanghai Cancer Institute Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Teladoc Health Inc Shanghai 200335China Shanghai Medical College Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention Shanghai 200032China

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.

关键词： miR-224-5p Exosome ULK2 p53 Cell proliferation Colorectal cancer

Garnet and Zircon U-Pb Geochronology and Geochemistry Reveal Genesis of the Dafang Au-Pb-Zn-Ag Deposit,Southern Hunan

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Acta Geologica Sinica(English Edition) 2024年第3期98卷 717-735页

作者： JIANG hua KONG hua liu Biao TAN Fucheng QIN Yixue huaNG Jingang ZHU Yu Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring Ministry of EducationSchool of Geosciences and Info-PhysicsCentral South UniversityChangsha 410083China School of Geosciences and Info-Physics Central South UniversityChangsha 410083China Hunan Baoshan Nonferrous Metals and Minerals Co. Ltd.ChenzhouHunan 424402China

Garnet is a primary mineral in skarn deposits and plays a significant role in recording copious mineralization and metallogenic information.This study systematically investigates the geochemistry and geochronology of garnet and zircon in the Dafang Au-Pb-Zn-Ag deposit,which represents prominent gold mineralization in southern Hunan,*** samples with distinct zoning patterns and compositional variations were identified using various analytical techniques,including Backscattered Electron(BSE)imaging,Cathodoluminescence(CL)response,textural characterization,and analysis of rare-earth elements(REE),major contents,and trace element compositions.The garnet was dated U-Pb dating,which yielded a lower intercept age of 161.06±1.93 Ma.This age is older than the underlying granodiorite porphyry,which has a concordia age of 155.13±0.95 Ma determined by zircon U-Pb dating.These results suggest that the gold mineralization may be related to the concealed granite.Two groups of garnet changed from depleted Al garnet to enriched Al garnet,and the rare earth element(REE)patterns of these groups were converted from light REE(LREE)-enriched and heavy REE(HREE)-depleted with positive europium(Eu)anomalies to medium REE(MREE)-enriched from core to rim zoning.The different REE patterns of garnet in various zones may be attributed to changes in the fluid environment and late superposition alteration.The development of distal skarn in the southern Hunan could be a significant indicator for identifying gold mineralization.

关键词： garnet and zircon U-Pb dating LA-ICP-MS mapping Dafang Southern Hunan