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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network Research center Sungkyunkwan University School of MedicineSuwonKorea Research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea drug Information Research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA

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National Science Review 2024年第3期11卷 72-91页

作者： Jiawang Zhou Haisheng Zhang Ke Zhong Lijun Tao Yu Lin Guoyou Xie Yonghuang Tan You Wu Yunqing Lu Zhuojia Chen Jiexin Li Xin Deng Qin Peng Zigang Li Hongsheng Wang Guangdong Provincial Key Laboratory of New drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat-sen University Sun Yat-sen University Cancer center State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine Department of Biomedical Sciences City University of Hong Kong Institute of systems and Physical Biology Shenzhen Bay Laboratory

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer（CRC） cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione（GSH） via the upregulation of RRM2B——a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3 UTR of RRM2B increased its m RNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence（CDS） of OPA1——an essential GTPase protein for mitochondrial inner membrane fusion——also increased m RNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

关键词： m6A mitochondrial fusion glutathione OPA1 colorectal cancer

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Cyclocarysaponins A–J, dammarane-type triterpenoid glycosides from the leaves of Cyclocarya paliurus

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Chinese Journal of Natural Medicines 2024年第10期22卷 955-964页

作者： XI Huiting YUAN Mingming XIE Jianhua WANG Yuanxing State Key Laboratory of Food Science and Resources Nanchang University Jiangxi Institute for drug Control NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine Jiangxi Provincial Engineering Research Center of Drug and Medical Device Quality

Ten previously undescribed dammarane-type triterpenoid glycosides, cyclocarysaponins A–J(1–10), were isolated from the leaves of Cyclocarya paliurus(Batal.) Iljinskaja. The structures of these compounds were characterized through detailed spectroscopic analysis, including 1D and 2D nuclear magnetic resonance(NMR) and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS). The cytotoxic activities of all isolates were assessed against five human cancer cell lines(Bel-7402, Caski, BGC-823, A2780, and HCT-116). Of the tested compounds, compounds 1, 7, and 9 exhibited selective cytotoxicity against one or more human cancer cell lines.

关键词： Cyclocarya paliurus Cyclocarysaponin Cytotoxic activities Juglandaceae Triterpenoid glycosides

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Data-driven Wasserstein distributionally robust chance-constrained optimization for crude oil scheduling under uncertainty

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Chinese Journal of Chemical Engineering 2024年第5期69卷 152-166页

作者： Xin Dai Liang Zhao Renchu He Wenli Du Weimin Zhong Zhi Li Feng Qian Key Laboratory of Smart Manufacturing in Energy Chemical Process Ministry of EducationEast China University of Science and TechnologyShanghai 200237China Engineering Research center of Process system Engineering Ministry of EducationEast China University of Science and TechnologyShanghai 200237China

Crude oil scheduling optimization is an effective method to enhance the economic benefits of oil *** uncertainties,including uncertain demands of crude distillation units(CDUs),might make the production plans made by the traditional deterministic optimization models infeasible.A data-driven Wasserstein distributionally robust chance-constrained(WDRCC)optimization approach is proposed in this paper to deal with demand uncertainty in crude oil ***,a new deterministic crude oil scheduling optimization model is developed as the basis of this *** Wasserstein distance is then used to build ambiguity sets from historical data to describe the possible realizations of probability distributions of uncertain demands.A cross-validation method is advanced to choose suitable radii for these ambiguity *** deterministic model is reformulated as a WDRCC optimization model for crude oil scheduling to guarantee the demand constraints hold with a desired high probability even in the worst situation in ambiguity *** proposed WDRCC model is transferred into an equivalent conditional value-at-risk representation and further derived as a mixed-integer nonlinear programming *** case studies from a real-world refinery are conducted to show the effectiveness of the proposed ***-of-sample tests demonstrate that the solution of the WDRCC model is more robust than those of the deterministic model and the chance-constrained model.

关键词： Distributions Model Optimization Crude oil scheduling Wasserstein distance Distributionally robust chance constraints

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Traditional Chinese medicines derived natural inhibitors of ferroptosis on ischemic stroke

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Chinese Journal of Natural Medicines 2024年第8期22卷 746-755页

作者： WANG Yongliang LAN Xiaobing LIU Ning MA Lin DU Juan WEI Wei HAI Dongmei WU Jing YU Jianqiang LIU Yue School of Pharmacy Ningxia Medical UniversityYinchuan 750000China Ningxia Key Laboratory of drug Development and Generic drug Research Ningxia Medical UniversityYinchuan 750000China Ningxia Characteristic Traditional Chinese Medicine Modern Engineering Research center Ningxia Medical UniversityYinchuan 750000China College of Basic Medical Sciences Ningxia Medical UniversityYinchuan 750000China

Ischemic stroke(IS)is a globally prevalent cerebrovascular disorder resulting from cerebral vessel occlusion,leading to significant morbidity and *** intricate pathological mechanisms underlying IS complicate the development of effective therapeutic ***,a form of programmed cell death(PCD)characterized by iron overload and accumulation of lipid peroxidation products,has been increasingly recognized as a key contributor to IS *** Chinese medicines(TCMs)have long been utilized in the management of IS,prompting extensive research into their potential as sources of natural ferroptosis *** review investigates the critical role of ferroptosis in IS and provides a comprehensive analysis of current research on natural ferroptosis inhibitors identified in TCMs,aiming to lay a theoretical groundwork for the development of innovative anti-IS therapies.

关键词： Ischemic stroke Traditional Chinese medicines Natural inhibitors Ferroptosis

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Knowledge Graph Completion Method of Combining Structural Information with Semantic Information

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Chinese Journal of Electronics 2024年

作者： Binhao HU Jianpeng ZHANG Hongchang CHEN School of Cyber Science and Engineering Zhengzhou University National Digital Switching system Engineering & Technological R&D center (NDSC)

With the development of knowledge graphs, a series of applications based on knowledge graphs have emerged. The incompleteness of knowledge graphs makes the effect of the downstream applications and affected by the quality of the knowledge graphs. To improve the quality of knowledge graphs, translation-based graph embeddings, such as TransE, learn structural information by rep-resenting triples as low-dimensional dense vectors. However, is difficult to generalize to unseen entities, Entities that are not observed during training but appear during testing. The other methods use the powerful representational ability of pre-trained language models to learn entity descriptions and contextual representation of triples. Although they are robust to incompleteness, but they need to calculate the score of all candidate entities for each triple during inference. We consider combining two models to enhance the robustness of unseen entities by semantic information, and prevent combined explosion by reducing inference overhead through structured information. We use a pre-training language model to code triples and learn the semantic information within them, and then use a hyperbolic space-based distance model to learn structural information and integrate the two types of information together. We evaluate our model by performing link prediction experi-ments in standard datasets. In experiments, our model achieves better performances than state-of-the-art methods on two standard datasets.

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In silico off-target profiling for enhanced drug safety assessment

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2927-2941页

作者： Jin Liu Yike Gui Jingxin Rao Jingjing Sun Gang Wang Qun Ren Ning Qu Buying Niu Zhiyi Chene Xia Sheng Yitian Wang Mingyue Zheng Xutong Li College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China drug Discovery and Design center State Key Laboratory of Drug ResearchShanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China University of Chinese Academy of Sciences Beijing 100049China Nanjing University of Chinese Medicine Nanjing 210023China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyHangzhou 330106China

Ensuring drug safety in the early stages of drug development is crucial to avoid costly failures in subsequent ***,the economic burden associated with detecting drug off-targets and potential side effects through in vitro safety screening and animal testing is *** off-target interactions,along with the adverse drug reactions they induce,are significant factors affecting drug *** assess the liability of candidate drugs,we developed an artificial intelligence model for the precise prediction of compound off-target interactions,leveraging multi-task graph neural *** outcomes of off-target predictions can serve as representations for compounds,enabling the differentiation of drugs under various ATC codes and the classification of compound ***,the predicted off-target profiles are employed in adverse drug reaction(ADR)enrichment analysis,facilitating the inference of potential ADRs for a *** the withdrawn drug Pergolide as an example,we elucidate the mechanisms underlying ADRs at the target level,contributing to the exploration of the potential clinical relevance of newly predicted off-target ***,our work facilitates the early assessment of compound safety/toxicity based on off-target identification,deduces potential ADRs of drugs,and ultimately promotes the secure development of drugs.

关键词： drug safety Off-target prediction Adverse drug reactions Toxicity Molecular representation Artificial intelligence

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Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Science China(Life Sciences) 2024年第6期67卷 1212-1225页

作者： Zhijie Hu Mengxia Li Yufeng Chen Liutao Chen Yuting Han Chengyong Chen Xin Lu Nan You Yawen Lou Yingye Huang Zhanfeng Huo Chao Liu Cheng Liang Susu Liu Ke Deng Liangfu Chen Shangwu Chen Guohui Wan Xiaojian Wu Yonggui Fu Anlong Xu State Key Laboratory of Biocontrol Guangdong Province Key Laboratory of Pharmaceutical Functional GenesDepartment of BiochemistrySchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China Department of General Surgery(Colorectal Surgery)&Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases&Biomedical Innovation center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China National-Local Joint Engineering Laboratory of druggability and New drug Evaluation National Engineering Research Center for New Drug and Druggability(cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well ***,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and *** found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and ***,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)*** results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

关键词： alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2

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Building stabilized Cu_(0.17)Mn_(0.03)V_(2)O_(5−□)·2.16H_(2)O cathode enables an outstanding room‐/low‐temperature aqueous Zn‐ion batteries

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Carbon Energy 2024年第8期6卷 25-35页

作者： Ao Wang Dai‐Huo Liu Lin Yang Fang Xu Dan Luo Haozhen Dou Mengqin Song Chunyan Xu Beinuo Zhang Jialin Zheng Zhongwei Chen Zhengyu Bai Key Laboratory of Green Chemical Media and Reactions Ministry of EducationCollaborative Innovation Center of Henan Province for Green Manufacturing of Fine ChemicalsSchool of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiangHenanChina The State Key Laboratory of Catalysis(SKLC) Power Battery and System Research CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalianChina

Vanadium oxide cathode materials with stable crystal structure and fast Zn^(2+)storage capabilities are extremely important to achieving outstanding electrochemical performance in aqueous zinc‐ion *** this work,a one‐step hydrothermal method was used to manipulate the bimetallic ion intercalation into the interlayer of vanadium *** pre‐intercalated Cu ions act as pillars to pin the vanadium oxide(V‐O)layers,establishing stabilized two‐dimensional channels for fast Zn^(2+)*** occupation of Mn ions between V‐O interlayer further expands the layer spacing and increases the concentration of oxygen defects(Od),which boosts the Zn^(2+)diffusion *** a result,as‐prepared Cu_(0.17)Mn_(0.03)V_(2)O_(5−□)·2.16H_(2)O cathode shows outstanding Zn‐storage capabilities under room‐and lowtemperature environments(e.g.,440.3 mAh g^(−1)at room temperature and 294.3 mAh g^(−1)at−60°C).Importantly,it shows a long cycling life and high capacity retention of 93.4%over 2500 cycles at 2 A g^(−1)at−60°***,the reversible intercalation chemistry mechanisms during discharging/charging processes were revealed via operando X‐ray powder diffraction and ex situ Raman *** strategy of a couple of 3d transition metal doping provides a solution for the development of superior room‐/lowtemperature vanadium‐based cathode materials.

关键词： aqueous zinc‐ion batteries Cu_(0.17)Mn_(0.03)V_(2)O_(5−□)·2.16H_(2)O oxygen defects room‐/lowtemperature performance stabilized nanostructure

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Soybean maize strip intercropping:A solution for maintaining food security in China

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Journal of Integrative Agriculture 2024年第7期23卷 2503-2506页

作者： Jiang Liu Wenyu Yang Sichuan Engineering Research center for Crop Strip Intercropping system/Key Laboratory of Crop Ecophysiology and Farming system in Southwest Ministry of Agriculture and Rural AffairsChengdu 611130China College of Life Science Sichuan Agricultural UniversityYa’an 625014China State Key Laboratory of Crop Gene Exploration and Utilization in Southwest China Chengdu 611130China

The practice of intercropping leguminous and gramineous crops is used for promoting sustainable agriculture,optimizing resource utilization,enhancing biodiversity,and reducing reliance on petroleum ***,promoting conventional intercropping strategies in modern agriculture can prove *** innovative technology of soybean maize strip intercropping(SMSI)has been proposed as a *** system has produced remarkable results in improving domestic soybean and maize production for both food security and sustainable *** this article,we provide an overview of SMSI and explain how it differs from traditional *** also discuss the core principles that foster higher yields and the prospects for its future development.

关键词： strip intercropping food security soybean maize spatial arrangement

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