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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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A sphingolipid message promotes neuronal health across generations

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Neural Regeneration Research 2024年第11期19卷 2325-2326页

作者： Wenyue Wang Roger Pocock development and Stem Cells Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Maternal nutrition can affect brain function of offspring in later life(Fitzgerald et al.,2020).Emerging studies have also shown that the maternal environment can modify susceptibility to neurodegenerative disease(Boots et al.,2023).Transmission of environmental information from mother to offspring depends on maternal nutrient *** the nematode Caenorhabditis elegans,maternal yolk,which is synthesized in the intestine and transferred to nourish oocytes and early embryos,can provide extranuclear inheritance factors to mediate phenotypic plasticity across ***,the molecular mechanisms of regulating such intergenerational effects remain largely unknown.

关键词： mother intestine transferred

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Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma

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Genes & Diseases 2024年第3期11卷 368-384页

作者： Yulu Shi Quan Kang Hong Zhou Xiaohan Yue Yang Bi Qing Luo Stem Cell Biology and Therapy Laboratory The Children's Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChongqing Key Laboratory of PediatricsChongqing 400014China department of Pediatric Surgery The Children's Hospital of Chongqing Medical UniversityChongqing 400014China

Osteosarcoma is a differentiation-deficient disease,and despite the unique advan-tages and great potential of differentiation therapy,there are only a few known differentia-tion inducers,and little research has been done on their *** differentiation is associated with an increase in mitochondrial content and *** metabolism of some tu-mor cells is characterized by impaired oxidative phosphorylation,as well as up-regulation of aerobic glycolysis and pentose phosphate ***-containing zipper and EF-hand transmembrane protein 1(LETM1)is involved in the maintenance of mitochondrial morphology and is closely associated with tumorigenesis and progression,as well as cancer cell *** found that MG63 and 143B osteosarcoma cells overexpress LETM1 and exhibit abnormalities in mitochondrial structure and *** of LETM1 partially restored the mitochon-drial structure and function,inhibited the pentose phosphate pathway,promoted oxidative phosphorylation,and led to osteogenic *** also inhibited spheroid cell forma-tion,proliferation,migration,and invasion in an in vitro *** LETM1 was knocked down in vivo,there was reduced tumor formation and lung *** data suggest that mitochondria are aberrant in LETM1-overexpressing osteosarcoma cells,and knockdown of LETM1 partially restores the mitochondrial structure and function,inhibits the pentose phosphate pathway,promotes oxidative phosphorylation,and increases osteogenic differentiation,thereby reducing malignant biological behavior of the cells.

关键词： Cancer metabolism Differentiation LETM1 Osteosarcoma Stemness

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Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids

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Genes & Diseases 2024年第2期11卷 1066-1081页

作者： Junyan Yan Lu Xiao Di Feng Baolin Chen Ting Yang Bei Tong Ruifang Luo Yuting Wang Jie Chen Children Nutrition Research Center Children's Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Child Nutrition and HealthMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing 401122China department of Gastroenterology Children's Hospital of Chongqing Medical UniversityChongqing 401122China

Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier ***-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is ***,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA *** the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were ***,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal *** study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its *** findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.

关键词： CEACAM1 Colonic epithelial barrier HDAC3 Short-chain fatty acids Vitamin A deficiency

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Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice

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Biomedical and Environmental Sciences 2024年第1期37卷 19-30页

作者： MENG Li Ying TAO Wen Fu LI Jing ZHU Min ZHONG De Bin ZHOU Jing QIN Xue WEI Rong Guo department of clinical Laboratory The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina department of clinical Laboratory The Fifth Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina Jiangsu Key Laboratory of Environmental Engineering Jiangsu Academy of Environmental SciencesNanjing 210000JiangsuChina

Objective The aim of this study was to assess the impact of bisphenol A(BPA)and its substitute,bisphenol F(BPF),on the colonic fecal community structure and function of *** We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg∙day)and 50μg/(kg∙day)of BPA or BPF for 14 *** samples from the colon were analyzed using 16S rRNA *** Gut microbiome community richness and diversity,species composition,and function were significantly altered in mice exposed to BPA or *** change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and ***,pathways related to carbohydrate and amino acid metabolism showed substantial *** Mice exposed to different BP analogs exhibited distinct gut bacterial community richness,composition,and related metabolic *** the essential role of gut bacteria in maintaining intestinal homeostasis,our study highlights the intestinal toxicity of BPs in vertebrates.

关键词： Bisphenol A(BPA) Bisphenol F(BPF) 16S rRNA Microbiota

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Experimental analysis of matrix moveable oil saturation in tight sandstone reservoirs of the south Ordos Basin,China

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Energy Geoscience 2024年第1期5卷 184-195页

作者： Ting Xu Jun Pu Xuejie Qin YiWei Science and Technology development department Petroleum Exploration&Production Research InstituteSINOPECBeijing100083China Center Research department of North China Petroleum Exploration&Production Research Institute SINOPECBeijing100083China Oil Field development department Petroleum Exploration&Production Research InstituteSINOPECBeijing100083China

Tight oil reservoirs in the south Ordos Basin are characterized by fractured,heterogeneous oil-bearing strata(an oil saturation of less than 55%on average),normal pressure(0.8±)and extra-low permeability(less than 0.3 mD).In the Chang 8 tight sandstone reservoir in Honghe oilfield,micro-and nanopores,especially those with a pore-throat radius of less than 1 mm,account for more than 90%.Fluid flow in the matrix is non-linear and crude oil flow rates are very low under normal pressure *** improved understanding of oil mobility in a tight matrix is key to further development of normalpressure tight-oil resources in the continental *** this study,constant-velocity and high-pressure mercury injection experiments were conducted using samples of typical tight sandstone cores obtained from the south of Ordos Basin.A new method for reconstructing the full-scale pore-throat distribution characteristics of tight sandstone reservoirs was established successfully,based on which multistage centrifugal tests,tests of low-pressure differential displacement of oil by water,and nuclear magnetic resonance tests were conducted in order to obtain the distribution characteristics of moveable fluid in different *** moveable oil saturation(MOS)and degree of oil recovery(*** of accumulative oil production to producing geologic reserves)of the core samples under different differential pressures for displacement were *** for the tight oil reservoirs in the south Ordos Basin,the moveable fluids are mainly stored in sub-micron(0.10-0.5 mm)*** Type I reservoirs(k>0.1 mD),the volume percentage of moveable fluid in pores with a radius larger than 0.5 mm is relatively high(greater than 40%).The degree of oil recovery of water flooding serves as the basis for forecasting recoverable reserves for tight oil *** reserves under water flooding,mainly occur in pores with a radius greater than 0.5 *** contribution of Type I reserves to oil pro

关键词： Tight reservoir Pore-throat structure Moveable fluid volume Moveable oil saturation(MOS) Waterflooding oil recovery South Ordos basin

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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration Research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University department of Neurology and clinical Research Center of Neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

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Mitochondrial dysfunction and quality control lie at the heart of subarachnoid hemorrhage

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Neural Regeneration Research 2024年第4期19卷 825-832页

作者： Jiatong Zhang Qi Zhu Jie Wang Zheng Peng Zong Zhuang Chunhua Hang Wei Li department of Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing University department of Neurosurgery Nanjing Drum Tower HospitalClinical College of Nanjing Medical University

The dramatic increase in intracranial pressure after subarachnoid hemorrhage leads to a decrease in cerebral perfusion pressure and a reduction in cerebral blood *** are directly affected by direct factors such as ischemia,hypoxia,excitotoxicity,and toxicity of free hemoglobin and its degradation products,which trigger mitochondrial *** mitochondria release large amounts of reactive oxygen species,inflammatory mediators,and apoptotic proteins that activate apoptotic pathways,further damaging *** response to this array of damage,cells have adopted multiple mitochondrial quality control mechanisms through evolution,including mitochondrial protein quality control,mitochondrial dynamics,mitophagy,mitochondrial biogenesis,and intercellular mitochondrial transfer,to maintain mitochondrial homeostasis under pathological *** interventions targeting mitochondrial quality control mechanisms have emerged as promising therapeutic strategies for subarachnoid *** review provides an overview of recent research advances in mitochondrial pathophysiological processes after subarachnoid hemorrhage,particularly mitochondrial quality control *** also presents potential therapeutic strategies to target mitochondrial quality control in subarachnoid hemorrhage.

关键词： mitochondrial biogenesis mitochondrial dynamics mitochondrial dysfunction mitochondrial fission and fusion mitochondrial quality control mitophagy subarachnoid hemorrhage

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A cup of coffee for a brain long life

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Neural Regeneration Research 2024年第1期19卷 158-159页

作者： Chiara Porro Antonia Cianciulli Maria Antonietta Panaro department of clinical and Experimental Medicine University of FoggiaFoggiaItaly(Porro C)Department of BiosciencesBiotechnologies and EnvironmentUniversity of BariBariItaly

Coffee is one of the world's favorite and most popular beverages,the third most popular beverage after water and *** many people,it is an indispensable habit before going to work and a socialization tool for the rest of the *** general,the average consum ption varies from 2 to6 cups per *** are the health implications?Given this consum ption,the benefits are actually greater than the *** is the conclusion of a careful study published in the New England Journal of Medicine(van Dam et al.,2020).

关键词： favorite conclusion life

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Recent advancement of sonogenetics:A promising noninvasive cellular manipulation by ultrasound

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Genes & Diseases 2024年第5期11卷 163-182页

作者： Jin Tang Mingxuan Feng Dong Wang Liang Zhang Ke Yang Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityNational Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Engineering Research Center of Stem Cell TherapyChongqing 400014China department of Ultrasound The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Tongji Medical College Huazhong University of Science and TechnologyWuhanHubei 430074China

Recent advancements in biomedical research have underscored the importance of noninvasive cellular manipulation ***,a method that uses genetic engineering to produce ultrasound-sensitive proteins in target cells,is gaining prominence along with optogenetics,electrogenetics,and *** stimulation with ultrasound,these proteins trigger a cascade of cellular activities and *** traditional ultrasound modalities,sonogenetics offers enhanced spatial selectivity,improving precision and safety in disease *** technology broadens the scope of non-surgical interventions across a wide range of clinical research and therapeutic applications,including neuromodulation,oncologic treatments,stem cell therapy,and *** current literature predominantly emphasizes ultrasonic neuromodulation,this review offers a comprehensive exploration of *** discuss ultrasound properties,the specific ultrasound-sensitive proteins employed in sonogenetics,and the technique’s potential in managing conditions such as neurological disorders,cancer,and ophthalmic diseases,and in stem cell *** objective is to stimulate fresh perspectives for further research in this promising field.

关键词： Mechanosensitive channel Neuromodulation Sonogenetics Ultrasound Ultrasound-sensitive protein

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