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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang guan-min jiang Hao Wang Department of Laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of Clinical Medicine Shandong UniversityJinanChina Core Unit of National Clinical Research Center for Laboratory Medicine HefeiChina Neurosurgical Department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Department of Clinical Laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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Epigenetic and post-translational modifications in autophagy:biological functions and therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第2期8卷 581-603页

作者： Feng Shu Han Xiao Qiu-Nuo Li Xiao-Shuai Ren Zhi-Gang Liu Bo-Wen Hu Hong-Sheng Wang Hao Wang guan-min jiang Department of Clinical Laboratory The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiGuangdongChina Cancer Center Affiliated Dongguan HospitalSouthern Medical UniversityDongguanGuangdongChina Department of Urology The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiGuangdongChina guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhouGuangdongChina Department of Clinical Laboratory The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhuiChina

Autophagy is a conserved lysosomal degradation pathway where cellular components are dynamically degraded and re-processed to maintain physical ***,the physiological effect of autophagy appears to be *** the one hand,autophagy functions as a cytoprotective mechanism,protecting against multiple diseases,especially tumor,cardiovascular disorders,and neurodegenerative and infectious ***,autophagy may also play a detrimental role via pro-survival effects on cancer cells or cell-killing effects on normal body *** disorder onset and progression,the expression levels of autophagy-related regulators and proteins encoded by autophagy-related genes(ATGs)are abnormally regulated,giving rise to imbalanced autophagy ***,the detailed mechanisms and molecular events of this process are quite ***,including DNA methylation,histone modifications and miRNAs,and post-translational modifications,including ubiquitination,phosphorylation and acetylation,precisely manipulate gene expression and protein function,and are strongly correlated with the occurrence and development of multiple *** is substantial evidence that autophagy-relevant regulators and machineries are subjected to epigenetic and post-translational modulation,resulting in alterations in autophagy levels,which subsequently induces disease or affects the therapeutic effectiveness to *** this review,we focus on the regulatory mechanisms mediated by epigenetic and post-translational modifications in disease-related autophagy to unveil potential therapeutic *** addition,the effect of autophagy on the therapeutic effectiveness of epigenetic drugs or drugs targeting post-translational modification have also been discussed,providing insights into the combination with autophagy activators or inhibitors in the treatment of clinical diseases.

关键词： therapeutic drugs protective

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Evolution exploration and structure prediction of Keggin-type group IVB metal-oxo clusters

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Chinese Chemical Letters 2024年第5期35卷 487-492页

作者： Run-Han Li Tian-Yi Dang Wei guan jiang Liu Ya-Qian Lan Zhong-min Su School of Chemistry South China Normal UniversityGuangzhou 510006China Institute of Functional Material Chemistry Faculty of ChemistryNortheast Normal UniversityChangchun 130024China Institute of Theoretical Chemistry Jilin UniversityChangchun 130023China

The fascinating chemical structure and broad application prospect of Keggin-type polyoxometalates(POMs)have attracted many chemists to explore and discover *** the traditional Keggin,larger metal atomic radius,higher metal coordinated numbers,lower metal valence states and other features allow the group IVB metal-based Keggin(IVB-Keggin)more space and unknown in terms of structure and ***,density functional theory(DFT)calculations were performed to explore the influences including cores,shells,caps,and terminal ligands,et *** IVB-Keggin,and analyze the possibility of novel structure *** the perspective of multi-layer onion-like clusters,molecular energy level,host-guest interaction energy,surface charge and covalent bond polarity can be further adjusted to achieve the oriented design of functional *** insights are expected to provide theoretical support for experimental synthesis,opening a new perspective to understand the growth of Keggin.

关键词： Keggin Metal-oxo clusters Group IVB Onion pattern DFT

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Could natural phytochemicals be used to reduce nitrogen excretion and excreta‑derived N_(2)O emissions from ruminants?

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Journal of Animal Science and Biotechnology 2024年第2期15卷 490-508页

作者： Yuchao Zhao ming Liu Linshu jiang Leluo guan Beijing Key Laboratory of Dairy Cow Nutrition College of Animal Science and TechnologyBeijing University of AgricultureBeijing 102206China College of Animal Science and Technology China Agricultural UniversityBeijing 100193China Department of Agricultural Food and Nutritional ScienceUniversity of AlbertaEdmontonAB T6G 2R3Canada

Ruminants play a critical role in our food system by converting plant biomass that humans cannot or choose not to consume into edible high-quality ***,ruminant excreta is a significant source of nitrous oxide(N_(2)O),a potent greenhouse gas with a long-term global warming potential 298 times that of carbon *** phytochemicals or forages containing phytochemicals have shown the potential to improve the efficiency of nitrogen(N)utilization and decrease N_(2)O emissions from the excreta of *** inclusion of tannins can shift more of the excreted N to the feces,alter the urinary N composition and consequently reduce N_(2)O emissions from *** oils or saponins could inhibit rumen ammonia production and decrease urinary N *** grazed pastures,large amounts of glucosinolates or aucubin can be introduced into pasture soils when animals consume plants rich in these compounds and then excrete them or their metabolites in the urine or *** inhibitory compounds are excreted in the urine,they would be directly applied to the urine patch to reduce nitrification and subsequent N_(2)O *** phytochemicals’role in sustainable ruminant production is undeniable,but much uncertainty ***,transient effects,and adverse effects limit the effectiveness of these phytochemicals for reducing N *** this review,we will identify some current phytochemicals found in feed that have the potential to manipulate ruminant N excretion or mitigate N_(2)O production and deliberate the challenges and opportunities associated with using phytochemicals or forages rich in phytochemicals as dietary strategies for reducing N excretion and excreta-derived N_(2)O emissions.

关键词： Nitrogen metabolism Nitrous oxide Plant bioactive compounds Ruminant Urine patches

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Quantum age of vector magnetic field measurements

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Science China(Physics,Mechanics & Astronomy) 2024年第10期67卷 164-165页

作者： min jiang CAS Key Laboratory of Microscale Magnetic Resonance and School of Physical Sciences University of Science and Technology of ChinaHefei 230026China

Magnetic fields are ubiquitous,and precise measurements of them can serve as powerful tools for deep understanding and accurate detection across multiple disciplines,including physics,biology,and chemistry[1].For instance,by measuring the magnetic fields within the human heart and brain,the medical community could obtain accurate disease diagnoses.

关键词： magnetic Quantum precise

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Effects of hot deformation and in-situ ZrB2 particle on microstructure and tensile performance of AA7085 composite sheets

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Journal of Iron and Steel Research International 2024年第7期31卷 1778-1791页

作者： jiang-jing Wu Xi-zhou Kai Chuang guan Yu-tao Zhao School of Material Science and Engineering Jiangsu UniversityZhenjiang 212013JiangsuChina

To provide a new idea to reduce anisotropy for sheets in the thickness direction by microstructure modification and,mean-while,maintain or even enhance tensile performance,the in-situ ZrB2 particle/AA7085 composite sheets with thicknesses of 1,2,3,and 6 mm were *** as-cast grain size was significantly refined by the heterogeneous nucleus of the ZrB2 *** microstructure results show that severe hot deformation converts as-cast disordered microstructure into a sequential microstructure by crushing the remanent phases and matrix into a fiber *** the solid solution and aging heat treatment,the composite sheets exhibit largely recrystallized grains compared with partially recrystallized grains in the matrix sheets,and weak or even free texture exists in the *** grain size in the composite sheets decreases with the increase in thickness *** the thickness range of 1-3 mm,the composite sheets maintain a similar tensile per-formance as that in matrix sheets,while the strength and ductility in the 6-mm-thick composite sheet are improved.

关键词： Composite sheet Grain structure Texture Dislocation Strengthening

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Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3063-3076页

作者： Wenjing Zai min Yang Kuan jiang Juan guan Huijing Wang Kongying Hu Chao Huang Jieliang Chen Wei Fu Changyou Zhan Zhenghong Yuan Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Research Unit of Cure of Chronic Hepatitis B Virus Infection(CAMS)Shanghai Frontiers Science Center of Pathogenic Microbes and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghaiP.R.China Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghaiP.R.China Shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghaiP.R.China Eye Institute and Department of Ophthamology Eye and ENT HospitalFudan UniversityShanghaiP.R.China Pharmacy Department of Huashan Hospital Fudan UniversityShanghaiP.R.China Institute of Pediatric Translational Medicine Shanghai Institute for Pediatric Congenital Heart DiseaseShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Institute of Infectious Disease and Biosecurity ShanghaiP.R.China

This study aimed to develop a pan-genotypic and multifunctional small interfering RNA(siRNA)against hepatitis B virus(HBV)with an efficient delivery system for treating chronic hepatitis B(CHB),and explore combined RNA interference(RNAi)and immune modulatory modalities for better viral *** synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and *** lipid nanoparticle(LNP)formulation was optimized by adopting HO-PEG_(2000)-DMG lipid and modifying the molar ratio of traditional polyethylene glycol(PEG)lipid in LNP *** efficacy and safety of this formulation in delivering siHBV(tLNP/siHBV)along with the mouse IL-2(mIL-2)mRNA(tLNP/siHBVIL2)were evaluated in the rAAVHBV1.3 mouse model.A siRNA combination(terms“siHBV”)with a genotypic coverage of 98.55%was selected,chemically modified,and encapsulated within an optimized LNP(tLNP)of high efficacy and security to fabricate a therapeutic formulation for *** results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA(up to 3log_(10)reduction;vs PBS)in dose-and time-dependent manners at single-dose or multi-dose frequencies,with satisfactory safety *** studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus,via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4^(+)and CD8^(+)T cell responses by expressed mIL-2 *** adopting tLNP as nucleic acid nanocarriers,the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV,thus offering a promising translational therapeutic strategy for treating CHB.

关键词： formulation enable offering

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Grasp Detection with Hierarchical Multi-Scale Feature Fusion and Inverted Shuffle Residual

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Tsinghua Science and Technology 2024年第1期29卷 244-256页

作者： Wenjie Geng Zhiqiang Cao Peiyu guan Fengshui Jing min Tan Junzhi Yu State Key Laboratory of Multimodal Artificial Intelligence Systems Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Artificial Intelligence University of Chinese Academy of SciencesBeijing 100049China Department of Advanced Manufacturing and Robotics College of EngineeringPeking UniversityBeijing 100871China

Grasp detection plays a critical role for robot *** pixel-wise grasp detection networks with encoder-decoder structure receive much attention due to good accuracy and ***,they usually transmit the high-level feature in the encoder to the decoder,and low-level features are *** is noted that low-level features contain abundant detail information,and how to fully exploit low-level features remains ***,the channel information in high-level feature is also not well ***,the performance of grasp detection is *** solve these problems,we propose a grasp detection network with hierarchical multi-scale feature fusion and inverted shuffle *** low-level and high-level features in the encoder are firstly fused by the designed skip connections with attention module,and the fused information is then propagated to corresponding layers of the decoder for in-depth feature *** a hierarchical fusion guarantees the quality of grasp ***,an inverted shuffle residual module is created,where the high-level feature from encoder is split in channel and the resultant split features are processed in their respective *** such differentiation processing,more high-dimensional channel information is kept,which enhances the representation ability of the ***,an information enhancement module is added before the encoder to reinforce input *** proposed method attains 98.9%and 97.8%in image-wise and object-wise accuracy on the Cornell grasping dataset,respectively,and the experimental results verify the effectiveness of the method.

关键词： grasp detection hierarchical multi-scale feature fusion skip connections with attention inverted shuffle residual

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Discovering deaminases using AlphaFold2:a strategy to search for tool proteins for gene editing

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Signal Transduction and Targeted Therapy 2024年第3期9卷 822-824页

作者： Yongye Huang Jianxin jiang min Wu Key Laboratory of Bioresource Research and Development of Liaoning Province College of Life and Health SciencesNortheastern UniversityShenyang 110169China Wound Trauma Medical Center State Key Laboratory of TraumaBurns and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042China Wenzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University WenzhouZhejiang 325000China Wenzhou Institute University of Chinese Academy of SciencesWenzhou 325000China The Joint Research Center Affiliated Xiangshan Hospital of Wenzhou Medical UniversityNingboChina

A recent study by Huang et *** in Cell reported the application of AlphaFold2 to forecast the structures of deaminase proteins and cluster them based on structural similarity,creating a truncated Sdd that can be used as a cytosine base editor(CBE)to be integrated into a single adeno-associated virus(AAV)1 This ground-breaking study aided by the artificial intelligence system would largely broaden the utility of tool proteins for gene editing.

关键词： CBE Alpha editor

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Microstructure evolution,mechanical properties and fracture behavior of Al-xSi/AZ91D bimetallic composites prepared by a compound casting

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Journal of Magnesium and Alloys 2024年第5期12卷 1944-1964页

作者： guangyu Li Wenming jiang Feng guan Junwen Zhu Yang Yu Zitian Fan State Key Laboratory of Materials Processing and Die&Mould Technology School of Materials Science and EngineeringHuazhong University of Science and TechnologyWuhan 430074China

In this paper,the effect of the Si content on microstructure evolution,mechanical properties,and fracture behavior of the Al-xSi/AZ91D bimetallic composites prepared by compound casting was investigated *** obtained results showed that all the Al-xSi/AZ91D bimetallic composites had a metallurgical reaction layer(MRL),whose thickness increased with increasing Si content for the hypoeutectic Al-Si/AZ91D composites,while the hypereutectic Al-Si/AZ91D composites were *** MRL included eutectic layer(E layer),intermetallic compound layer(IMC layer)and transition region layer(T layer).In the IMC layer,the hypereutectic Al-Si/AZ91D composites contained some Si solid solution and flocculent Mg_(2)Si+Al-Mg IMCs phases not presented in the hypoeutectic Al-Si/AZ91D ***,increasing Si content,the thickness proportion of the T layer increased,forming an inconsistent preferred orientation of the *** shear strengths of the Al-xSi/AZ91D bimetallic composites enhanced with increasing Si content,and the Al-15Si/AZ91D composite obtained a maximum shear strength of 58.6 MPa,which was 73.4% higher than the Al-6Si/AZ91D *** fractures of the Al-xSi/AZ91D bimetallic composites transformed from the T layer into the E layer with the increase of the Si *** improvement of the shear strength of the Al-xSi/AZ91D bimetallic composites was attributed to the synergistic action of the Mg_(2)Si particle reinforcement,the reduction of oxidizing inclusions and the ratio of Al-Mg IMCs as well as the orientation change of the MRL.

关键词： Al/Mg bimetallic composites Si content Mg_(2)Si reinforcement Microstructure Mechanical properties Fracture behavior

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