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Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

Neural Regeneration Research 2024年第6期19卷 1256-1261页

作者： Helen M.Knight Merve Demirbugen ?z Adriana PerezGrovas-Saltijeral Division of Cells Organisms and Molecular Genetics School of Life Sciences University of Notingham Department of Pharmaceutical Toxicology Faculty of Pharmacy Ankara University

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms. Methylation of N6 adenosine(m6A) and C5 cytosine(m5C) bases occur on mRNAs, tRNA, mt-tRNA, and rRNA species as well as non-coding RNAs. With emerging knowledge of RNA binding proteins that act as writer, reader, and eraser effector proteins, comes a new understanding of physiological processes controlled by these systems. Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain, give rise to different forms of disease. In this review, we discuss accumulating evidence that changes in the m6A and m5C methylation systems contribute to neurocognitive disorders. Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m6A RNA reader protein. Subsequently, familial mutations within the m6A writer gene METTL5, m5C writer genes NSUN2, NSUN3, NSUN5, and NSUN6, as well as THOC2 and THOC6 that form a protein complex with the m5C reader protein ALYREF, were recognized to cause intellectual development disorders. Similarly, differences in expression of the m5C writer and reader effector proteins, NSUN6, NSUN7, and ALYREF in brain tissue are indicated in individuals with Alzheimer’s disease, individuals with a high neuropathological load or have suffered traumatic brain injury. Likewise, an abundance of m6A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases, Alzheimer’s disease, and individuals with high cognitive reserve. m6A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson’s disease tissue, whilst modified RNAs are misplaced within diseased cells, particularly where synapses are located. In parahippocampal brain tissue, m6A modification is en

关键词： 5-methylcytosine methylation Alzheimer's disease cognitive diseases epitranscriptomics intellectual disability Lewy body diseases N6 adenosine RNA modification

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Structural insight into the dual-antagonistic mechanism of AB928 on adenosine A_(2)receptors

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Science China(life sciences) 2024年第5期67卷 986-995页

作者： Yuan Weng Xinyu Yang Qiansen Zhang Ying Chen Yueming Xu Chenyu Zhu Qiong Xie Yonghui Wang Huaiyu Yang Mingyao Liu Weiqiang Lu Gaojie Song Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China

The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy *** of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal ***,the precise mechanism underlying its dual-antagonistic properties remains ***,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist *** structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary *** contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)*** analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic *** disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)*** study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.

关键词： adenosine receptor A2AR A2BR inhibitor dual-antagonism drug discovery

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Effects of host identity on the gut microbiota:A comparative study on three microtinae species

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Animal Models and Experimental Medicine 2024年第2期7卷 98-105页

作者： Zhen Yao Wenli Zhao Baohong Tang Qinghua Li Zhenlong Wang school of life sciences Zhengzhou UniversityZhengzhouHenan ProvinceP.R.China

Background:Gut microbiota exert an immense effect on host health and host environmental ***,the composition and structure of gut microbiota are determined by the environment and host genetic ***,the relative contribution of the environment and host genetic factors toward shaping the structure of gut microbiota has been poorly ***:In this study,we characterized the fecal microbial communities of the closely related voles Neodon fuscus,Lasiopodomys brandtii,and *** after caged feeding in the laboratory for 6 months,through high-throughput sequencing and bioinformatics ***:The results of pairwise comparisons of *** *** and *** *** revealed significant differences in bacterial diversity and composition after *** 991 same operational taxonomic units(OTUs)were shared in three voles,there were 362,291,and 303 species-specific OTUs in ***,***,and ***,*** relative abundances of Proteobacteria and Prevotella,which are reported to be enriched in high-altitude populations,were significantly higher in high-altitude *** than in low-altitude *** after ***,which produce various digestive enzymes for energy metabolism,and Spirochaetes,which can degrade cellulose,were found in higher abundance in subterranean *** than that in *** which dwells on the earth ***:Our findings showed that some components of gut microbiota still maintained dominance even when different host species are reared under the same environmental conditions,suggesting that these bacteria are substantially influenced by host factors.

关键词： gut microbiota high-altitude Lasiopodomys brandtii Neodon fuscus

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Advances in environmental DNA monitoring:standardization,automation,and emerging technologies in aquatic ecosystems

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Science China(life sciences) 2024年第7期67卷 1368-1384页

作者： Suxiang Lu Honghui Zeng Fan Xiong Meng Yao Shunping He State Key Laboratory of Freshwater Ecology and Biotechnology Institute of HydrobiologyChinese Academy of SciencesWuhan 430072China Institute of Ecology College of Urban and Environmental SciencesPeking UniversityBeijing 100871China school of life sciences Peking UniversityBeijing 100871China Institute of Deep Sea Science and Engineering Chinese Academy of SciencesSanyaChina Center for Excellence in Animal Evolution and Genetics Chinese Academy of SciencesKunmingChina

environmental DNA(eDNA)monitoring,a rapidly advancing technique for assessing biodiversity and ecosystem health,offers a noninvasive approach for detecting and quantifying species from various environmental *** this review,a comprehensive overview of current eDNA collection and detection technologies is provided,emphasizing the necessity for standardization and automation in aquatic ecological ***,the intricacies of water bodies,from streams to the deep sea,and the associated challenges they pose for eDNA capture and analysis are *** paper delineates three primary eDNA survey methods,namely,bringing back water,bringing back filters,and bringing back data,each with specific advantages and constraints in terms of labor,transport,and data ***,innovations in eDNA sampling equipment,including autonomous drones,subsurface samplers,and in-situ filtration devices,and their applications in monitoring diverse taxa are ***,recent advancements in species-specific detection and eDNA metabarcoding are addressed,highlighting the integration of novel techniques such as CRISPR-Cas and nanopore sequencing that enable precise and rapid detection of *** implications of environmental RNA and epigenetic modifications are considered for future applications in providing nuanced ecological ***,the review stresses the critical role of standardization and automation in enhancing data consistency and comparability for robust long-term *** propose that the amalgamation of these technologies represents a paradigm shift in ecological monitoring,aligning with the urgent call for biodiversity conservation and sustainable management of aquatic ecosystems.

关键词： eDNA methodology sampler environment biomonitoring ecogenomic sensors ocean observation instrument

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Breeding exceptionally fragrant soybeans for soy milk with strong aroma

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Journal of Integrative Plant Biology 2024年第4期66卷 642-644页

作者： Hongtao Xie Minglei Song Xuesong Cao Qingfeng Niu Jianhua Zhu Shasha Li Xin Wang Xiaomu Niu Jian-Kang Zhu Bellagen Biotechnology Co.Ltd. Jinan 250000China Institute of Advanced Biotechnology and school of life sciences Southern University of Science and TechnologyShenzhen 518055China school of life sciences Anhui Agricultural UniversityHefei 230036China Shandong Normal University Jinan 250000China

Soybean(Glycine max(L.)Merr.)is a major source of vegetable protein and oil in human diet and animal *** seeds have been extensively used in various food products and *** quality,particularly the aroma,affects cooking and eating,and ultimately influences consumer *** milk is particularly popular in China and has been gaining popularity in many other countries in the world.

关键词： exceptional soybean cooking

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Carbonic anhydrase-like enzymes in the formation of Lycopodium alkaloid

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Chinese Journal of Natural Medicines 2024年第3期22卷 193-194页

作者： DONG Huiwen GE Huiming State key Laboratory of Pharmaceutical Biotechnology Institute of Functional BiomoleculesSchool of Life SciencesNanjing UniversityNanjing 210023China

Plant alkaloids,renowned for their structural diversity and bioactivity,are prominent in both modern and traditional medicine[1].Unraveling the intricacies of plant alkaloid biosynthesis could pave the way for the discovery of new natural products and *** may also shed light on the roles of existing pathways in host biology and provide valuable tools for metabolic engineering in plants and microbes[2].Unlike other major classes of plant natural products,such as terpenoids and polyketides,the formation of alkaloid scaffolds does not conform to a uniform chemical theme or depend on a singular enzyme class[3].A case in point is the Lycopodium alkaloids in the Lycopodiaceae family,where the enzymes responsible for their core scaffold construction remain unidentified[4].

关键词： Lycopodium alkaloid Carbonic anhydrase-like enzymes Biosynthesis

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Long way up:rethink diseases in light of phase separation and phase transition

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Protein & Cell 2024年第7期15卷 475-492页

作者： Mingrui Ding Weifan Xu Gaofeng Pei Pilong Li State Key Laboratory of Membrane Biology&Frontier Research Center for Biological Structure School of Life SciencesTsinghua UniversityBeijing 100084China Tsinghua-Peking Center for life sciences Beijing 100084China NuPhase Therapeutics Beijing 100083China

Biomolecular condensation, driven by multivalency, serves as a fundamental mechanism within cells, facilitating the formation of distinct compartments, including membraneless organelles that play essential roles in various cellular processes. Perturbations in the delicate equilibrium of condensation, whether resulting in gain or loss of phase separation, have robustly been associated with cellular dysfunction and physiological disorders. As ongoing research endeavors wholeheartedly embrace this newly acknowledged principle, a transformative shift is occurring in our comprehension of disease. Consequently, significant strides have been made in unraveling the profound relevance and potential causal connections between abnormal phase separation and various diseases. This comprehensive review presents compelling recent evidence that highlight the intricate associations between aberrant phase separation and neurodegenerative diseases, cancers, and infectious diseases. Additionally, we provide a succinct summary of current efforts and propose innovative solutions for the development of potential therapeutics to combat the pathological consequences attributed to aberrant phase separation.

关键词： multivalency compartments aberant phase separation therapeutics gain or loss of phase separation diseases

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Planetary Homeostasis of Reactive Nitrogen Through Anaerobic Ammonium Oxidation

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Engineering 2024年第7期38卷 175-183页

作者： Guibing Zhu Bangrui Lan Shuci Liu Cameron M.Callbeck Shanyun Wang Liping Jiang Asheesh Kumar Yadav Jan Vymazal Mike S.M.Jetten Ganlin Zhang Yongguan Zhu Research Center for Eco-environmental sciences Chinese Academy of SciencesBeijing 100085China Department of Environment and Science Queensland GovernmentBrisbaneQLD 4102Australia Department of environmental sciences University of BaselBasel 4056Switzerland CSIR-Institute of Minerals and Materials Technology Bhubaneswar 751013India Faculty of environmental sciences Czech University of Life Sciences PraguePraha 16521Czech Republic Department of Microbiology Radboud UniversityNijmegen 6525 XZThe Netherlands Key Laboratory of Watershed Geographic sciences Nanjing Institute of Geography and LimnologyChinese Academy of SciencesNanjing 210008China State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China University of Chinese Academy of sciences Beijing 100049China

The availability of nitrogen(N)is crucial for both the productivity of terrestrial and aquatic ecosystems ***,the overuse of artificial fertilizers and the energy required to fix nitrogen have pushed the global nitrogen cycle(N-cycle)past its safe operating limits,leading to severe nitrogen pollution and the production of significant amounts of greenhouse gas nitrous oxide(N2O).The anaerobic ammonium oxidation(anammox)mechanism can counteract the release of ammonium and N2O in many oxygenlimited situations,assisting in the restoration of the homeostasis of the Earth’s N *** this work,we looked into the characteristics of the anammox hotspots’distribution across various types of ecosystems *** hotspots are present at diverse oxic-anoxic interfaces in terrestrial systems,and they are most prevalent at the oxic-anoxic transition zone in aquatic *** on the discovery of an anammox hotspot capable of oxidizing ammonium anoxically into N2 without N2O by-product,we then designed an innovative concept and technical routes of nature-based anammox hotspot geoengineering for climate change,biodiversity loss,and efficient utilization of water *** 15 years of actual use,anammox hotspot geoengineering has proven to be effective in ensuring clean drinking water,regulating the climate,fostering plant and animal diversity,and enhancing longterm environmental *** sustainable biogeoengineering of anammox could be a workable natural remedy to resolve the conflicts between environmental pollution and food security connected to N management.

关键词： Biogeochemical N-cycle Oxic-anoxic interface Nature-based solution Biogeoengineering Nitrogen sustainable development

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Facilitated Prediction of Micropollutant Degradation via UV-AOPs in Various Waters by Combining Model Simulation and Portable Measurement

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Engineering 2024年第6期37卷 87-95页

作者： Yanyan Huang Mengkai Li Zhe Sun Wentao Li James R.Bolton Zhimin Qiang Key Laboratory of Drinking Water Science and Technology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China University of Chinese Academy of sciences Beijing 100049China Department of Civil and environmental Engineering University of AlbertaEdmontonAB T6G 1H9Canada State Key Laboratory of environmental Aquatic Chemistry Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China

The degradation of micropollutants in water via ultraviolet(UV)-based advanced oxidation processes(AOPs)is strongly dependent on the water *** reactive radicals(RRs)formed in UV-AOPs have different reaction selectivities toward water matrices and degradation efficiencies for target ***,process selection and optimization are *** study developed a facilitated prediction method for the photon fluence-based rate constant for micropollutant degradation(K′_(p,MP))in various UV-AOPs by combining model simulation with portable *** methods for measuring the scavenging capacities of the principal RRs(RRSCs)involved in UV-AOPs(i.e.,HO^(·),SO_(4)^(·-),and Cl^(·))using a mini-fluidic photoreaction system were *** simulation models consisted of photochemical,quantitative structure–activity relationship,and radical concentration steady-state approximation *** RRSCs were determined in eight test waters,and a higher RRSC was found to be associated with a more complex water ***,by taking sulfamethazine,caffeine,and carbamazepine as model micropollutants,the k′_(p,MP) values in various UV-AOPs were predicted and further verified experimentally.A lower k′_(p,MP) was found to be associated with a higher RRSC for a stronger RR competition;for example,k′_(p,MP) values of 130.9 and 332.5 m^(2) einstein^(–1),respectively,were obtained for carbamazepine degradation by UV/H_(2)O_(2) in the raw water(RRSC=9.47×10^(4) s^(-1))and sand-filtered effluent(RRSC=2.87×10^(4) s^(-1))of a drinking water treatment *** developed method facilitates process selection and optimization for UV-AOPs,which is essential for increasing the efficiency and cost-effectiveness of water treatment.

关键词： UV-AOPs Micropollutant degradation Reactive radicals Water matrix Model simulation

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Opportunities and challenges in studies of mammalian hybrid speciation

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Science China(life sciences) 2024年第3期67卷 614-617页

作者： Hong Wu Yuxing Zhang Li Yu State Key Laboratory for Conservation and Utilization of Bio-Resource in Yunnan School of Life SciencesYunnan UniversityKunming 650091China

Revealing the mechanisms of speciation remains one of the most attractive and challenging issues in the field of evolutionary biology, and is also key to understanding the biodiversity present in nature.

关键词： biodiversity attractive evolutionary

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