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Pivotal role for long noncoding RNAs in zygotic genome activation in mice

Science China(Life Sciences) 2024年第5期67卷 958-969页

作者： Kang chen Wenju Liu Jiang Zhu Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong gao lan Kang Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Clinical and Translation Research Center of Shanghai First Maternity&Infant Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains unclear.The existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ZGA.Here,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor ZGA.Compared with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor ZGA.Distinct H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII pre-configuration.Furthermore,we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo development.Our study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

关键词： ZGA lncRNA MuERV-L

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Chronic stress as an emerging risk factor for the development and progression of glioma

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Chinese Medical Journal 2024年第4期137卷 394-407页

作者： lan Yi Xiang Lin Xiaoling She Wei gao Minghua Wu Institute of Cytology and Genetics The Hengyang Key Laboratory of Cellular Stress BiologyHunan Province Cooperative Innovation Center for Molecular Target New Drug StudyHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China Department of Pathology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education Cancer Research InstituteCentral South UniversityChangshaHunan 410008China NHC Key Laboratory of Carcinogenesis Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system.Compared with patients with other cancers,glioma patients often suffer from increased levels of psychological stress,such as anxiety and fear.Chronic stress(CS)is thought to impact glioma profoundly.However,because of the complex mechanisms underlying CS and variability in individual tolerance,the role of CS in glioma remains unclear.This review suggests a new proposal to redivide the stress system into two parts.Neuronal activity is dominant upstream.Stress-signaling molecules produced by the neuroendocrine system are dominant downstream.We discuss the underlying molecular mechanisms by which CS impacts glioma.Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.

关键词： Chronic stress Glioma Microbiota-gut-brain axis Neuroendocrine system Stress system Neural circuit

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Wind disturbance compensated path-following control for fixed-wing UAVs in arbitrarily strong winds

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Chinese Journal of Aeronautics 2024年第2期37卷 431-445页

作者： Hao LU lan gao Yunda YAN Mingzhe HOU chenliang WANG Hangzhou Innovation Institute Beihang UniversityHangzhou 310051China School of Information Science and Technology Hangzhou Normal UniversityHangzhou 311121China Department of Computer Science University College LondonLondon WC1E 6BTUnited Kingdom Center for Control Theory and Guidance Technology Harbin Institute of TechnologyHarbin 150001China School of Automation Science and Electrical Engineering Beihang UniversityBeijing 100191China

Wind is the primary challenge for low-speed fixed-wing unmanned aerial vehicles to follow a predefined flight path.To cope with various wind conditions,this paper proposes a wind disturbance compensated path following control strategy where the wind disturbance estimate is incorporated with the nominal guiding vector field to provide the desired airspeed direction for the inner-loop.Since the control input vector for the outer-loop kinematic subsystem needs to satisfy a magnitude constraint,a scaling mechanism is introduced to tune the proportions of the compensation and nominal components.Moreover,an optimization problem is formulated to pursue a maximum wind compensation in strong winds,which can be solved analytically to yield two scaling factors.A cascaded inner-loop tracking controller is also designed to fulfill the outer-loop wind disturbance compensated guiding vector field.High-fidelity simulation results under sensor noises and realistic winds demonstrate that the proposed path following algorithm is less sensitive to sensor noises,achieves promising accuracy in normal winds,and mitigates the deviation from a desired path in wild winds.

关键词： Path following Guiding vector field Wind disturbance Disturbance rejection Fixed wings

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G protein-coupled receptors(GPCRs):advances in structures,mechanisms,and drug discovery

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1938-1980页

作者： Mingyang Zhang Ting chen Xun Lu Xiaobing lan Ziqiang chen Shaoyong Lu Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Cardiology Changzheng HospitalAffiliated to Naval Medical UniversityShanghai 200003China Department of Orthopedics Changhai HospitalAffiliated to Naval Medical UniversityShanghai 200433China

G protein-coupled receptors(GPCRs),the largest family of human membrane proteins and an important class of drug targets,play a role in maintaining numerous physiological processes.Agonist or antagonist,orthosteric effects or allosteric effects,and biased signaling or balanced signaling,characterize the complexity of GPCR dynamic features.In this study,we first review the structural advancements,activation mechanisms,and functional diversity of GPCRs.We then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five years.Particularly,an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric mechanisms.Finally,we highlight how the widespread GPCR-druggable allosteric sites can guide structure-or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family.

关键词： steric designing mechanisms

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Synergistic effects and kinetics analysis for co-pyrolysis of vacuum residue and plastics

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Frontiers of Chemical Science and Engineering 2024年第5期18卷 71-81页

作者： Chao Wang Xiaogang Shi Aijun Duan Xingying lan Jinsen gao Qingang Xiong State Key Laboratory of Heavy Oil Processing China University of Petroleum-BeijingBeijing 102249China State Key Laboratory of Pulp and Paper Engineering South China University of TechnologyGuangzhou 510640China

This study utilizedathermogravimetric analyzer to assess the thermal decomposition behaviors and kinetics properties of vacuum residue(VR)and low-density polyethylene(LDPE)polymers.The kinetic parameters were calculated using the Friedman technique.To demonstrate the interactive effects between LDPE and VR during the co-pyrolysis process,the disparity in mass loss and mass loss rate between the experimental and calculated values was computed.The co-pyrolysis curves obtained through estimation and experimentation exhibited significantdeviations,whichwerei influencedby temperature and mixing ratio.A negative synergistic interaction was observed between LDPE and VR,although this inhibitory effect could be mitigated or eliminated by reducing the LDPE ratio in the mixture and increasing the co-pyrolysistemperature.Theco-pyrolysisprocess resulted in a reduction in carbon residue,which could be attributed to the interaction between LDPE and the heavy fractions,particularly resin and asphaltene,present in VR.These findings align with the pyrolysis behaviors exhibited by the four VR fractions.Furthermore,it was observed that the co-pyrolysis process exhibited lower activation energy as the VR ratio increased,indicating a continuous enhancement in the reactivity of the mixed samples during co-pyrolysis.

关键词： co-pyrolysis heavy residual oil polyethylene thermogravimetric analysis synergistic effects

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A novel alternative for pyrogen detection based on a transgenic cell line

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1221-1229页

作者： Qing He Chuan-Fei Yu Gang Wu Kai-Qin Wang Yong-Bo Ni Xiao Guo Zhi-Hao Fu lan Wang De-Jiang Tan Hua gao Can Wang Gang chen Xu-Hong chen Bo chen Jun-Zhi Wang National Institutes for Food and Drug Control BeijingChina School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyangChina Shanghai Institute for Food and Drug Control ShanghaiChina KeyMed Biosciences Inc. ChengduChina

Pyrogen,often as a contaminant,is a key indicator affecting the safety of almost all parenteral drugs(including biologicals,chemicals,traditional Chinese medicines and medical devices).It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted‘reduction,replacement and refinement’principle,which has been highly considered by regulatory agencies from different countries.We used NF-κB,a central signalling molecule mediating inflammatory responses,as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal.Here,we show that this test can quantitatively and sensitively detect endotoxin(lipopolysaccharide from different strains)and nonendotoxin(lipoteichoic acid,zymosan,peptidoglycan,lectin and glucan),has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals(group A&C meningococcal polysaccharide vaccine;basiliximab;rabies vaccine(Vero cells)for human use,freeze-dried;Japanese encephalitis vaccine(Vero cells),inactivated;insulin aspart injection;human albumin;recombinant human erythropoietin injection(CHO Cell)).The within-laboratory reproducibility of the test in three independent laboratories was 85%,80%and 80%and the interlaboratory reproducibility among laboratories was 83.3%,95.6%and 86.7%.The sensitivity(true positive rate)and specificity(true negative rate)of the test were 89.9%and 90.9%,respectively.In summary,the test provides a novel alternative for pyrogen detection.

关键词： pyrogen rabbit replace

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Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies:A New Paradigm of"State-Target Medicine"

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Chinese Journal of Integrative Medicine 2022年第6期28卷 560-566页

作者： SHEN Feng-lin ZHAO Yan-na YU Xiao-ling WANG Bo-lin WU Xiao-long lan gao-chen gao Rui-lan Institute of Hematology Research The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310006China

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies(HMs).Targeted therapy,aiming for DNA methylation,is an effective mainstay of modem medicine;however,many issues remain to be addressed.The progress of epigenetic studies and the proposed theory of"state-target medicine"have provided conditions to form a new treatment paradigm that combines the"body state adjustment"of CM with targeted therapy.We discussed the correlation between Chinese medicine(CM)syndromes/states and DNA methylation in this paper.Additionally,the latest research findings on the intervention and regulation of DNA methylation in HMs,including the core targets,therapy status,CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of"state-target synchronous conditioning"pattern of integrative medicine for HMs,simultaneously leading a new perspective in clinical diagnosis and therapy.

关键词： haematological malignancies DNA methylation Chinese medicine state-target medicine

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Link Prediction Method Fusion with Local Structural Entropy for Directed Network

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Chinese Journal of Electronics 2024年第1期33卷 204-216页

作者： Shuxin LIU Hongchang chen lan WU Kai WANG Xing LI People’s Liberation Army Strategic Support Force Information Engineering University

Link prediction utilizes accessible network information to complement or predict the network links.Similarity is an important prerequisite for link prediction which means links more likely occurs between two similar nodes. Existing methods utilize the similarity of nodes but neglect of network structure. However the link direction leads to a far more complex structure and contains more information useful than the undirected networks. Most classic methods are difficult to depict the distribution of the network structure with incidental direction so the similarity characteristics of the network structure itself are lost. In this respect, a new method of local structure entropy is proposed to depict the directed structural distribution characteristics, which can be used to evaluate the degree of local structural similarity of nodes and then applied to link prediction methods. Experimental results on 8 real directed networks show that this method is effective for both area under the receiver operating characteristic curve(AUC)and ranking-score measures, and improved predictive capacity of the baseline methodology.

关键词： Local structural entropy Structural complexity Similar nodes Link prediction

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Monothetic and conductive network and mechanical stress releasing layer on micron-silicon anode enabling high-energy solid-state battery

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Rare Metals 2024年第3期43卷 1017-1029页

作者： Xiang Han Min Xu lan-Hui Gu Chao-Fei lan Min-Feng chen Jun-Jie Lu Bi-Fu Sheng Peng Wang Song-Yan chen Ji-Zhang chen College of Materials Science and Engineering Co-Innovation Center of Efficient Processing and Utilization of Forestry ResourcesNanjing Forestry UniversityNanjing210037China Department of Physics Xiamen UniversityXiamen361005China Western Digital Corporation MilpitasCA95035USA

Silicon has ultrahigh capacity,dendrite-free alloy lithiation mechanism and low cost and has been regarded as a promising anode candidate for solid-state battery.Owing to the low infiltration of solid-state electrolyte(SSE),not the unstable solid-electrolyte interphase(SEI),but the huge stress during lithiation-and delithiation-induced particle fracture and conductivity lost tend to be the main issues.In this study,starting with micron-Si,a novel monothetic carbon conductive framework and a MgO coating layer are designed,which serve as electron pathway across the whole electrode and stress releasing layer,respectively.In addition,the in situ reaction between Si and SSE helps to form a LiF-rich and mechanically stable SEI layer.As a result,the mechanical stability and charge transfer kinetics of the uniquely designed Si anode are significantly improved.Consequently,high initial Coulombic efficiency,high capacity and durable cycling stability can be achieved by applying the Si@MgO@C anode in SSB.For example,high specific capacity of 3224.6 mAh·g^(-1)and long cycling durability of 200 cycles are achieved.This work provides a new concept for designing alloy-type anode that combines surface coating on particle and electrode structure design.

关键词： Lithium-ion battery(LIB) Solid-state electrolyte(SSE) Silicon anode Stress relief Coating

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Effect of multiple coulomb scattering on the beam tests of silicon pixel detectors

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Nuclear Science and Techniques 2024年第4期35卷 200-207页

作者： lan-Kun Li Ming-Yi Dong Ze gao Liang-cheng-Long Jin Shu-Jun Zhao School of Physics and Microelectronics Zhengzhou UniversityZhengzhou 450001China State Key Laboratory of Particle Detection and Electronics(Institute of High Energy Physics CAS)Beijing 100049China University of Chinese Academy of Science Beijing 100049China University of South China Hengyang 421001China

In the research and development of new silicon pixel detectors,a collimated monoenergetic charged-particle test beam equipped with a high-resolution pixel-beam telescope is crucial for prototype verification and performance evaluation.When the beam energy is low,the effect of multiple Coulomb scattering on the measured resolution of the Device Under Test(DUT)must be considered to accurately evaluate the performance of the pixel chips and detectors.This study aimed to investigate the effect of multiple Coulomb scattering on the measured resolution,particularly at low beam energies.Simulations were conducted using Allpix^(2) to study the effects of multiple Coulomb scattering under different beam energies,material budgets,and telescope layouts.The simulations also provided the minimum energy at which the effect of multiple Coulomb scattering could be ignored.Compared with the results of a five-layer detector system tested with an electron beam at DESY,the simulation results were consistent with the beam test results,confirming the reliability of the simulations.

关键词： Silicon Pixel Detectors Beam Telescope Multiple Coulomb Scattering Spatial Resolution

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