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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 cells.Relevant studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of therapeutics.As a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular phenotypes.To be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts.In 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 types.Then 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 metabolism.And we highlight the regulation of RNA modifications on immunometabolism,further influencing immune responses.Above 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 therapeutics.Eventually,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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Postponed and reduced basal nitrogen application improves nitrogen use efficiency and plant growth of winter wheat

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Journal of Integrative Agriculture 2018年第12期17卷 2648-2661页

作者： tian zhong-wei LIU Xiao-xue GU Shi-lu YU Jin-hong ZHANG Lei ZHANG wei-wei JIANG Dong CAO wei-xing DAI Ting-bo Key Laboratory of Crop Physiology Ecology and Production Management Ministry of Agriculture/College of AgricultureNanjing Agricultural University

Excessive nitrogen(N) fertilization with a high basal N ratio in wheat can result in lower N use efficiency(NUE) and has led to environmental problems in the Yangtze River Basin, China. However, wheat requires less N fertilizer at seedling growth stage, and its basal N fertilizer utilization efficiency is relatively low; therefore, reducing the N application rate at the seedling stage and postponing the N fertilization period may be effective for reducing N application and increasing wheat yield and NUE. A 4-year field experiment was conducted with two cultivars under four N rates(240 kg N ha–1(N240), 180 kg N ha–1(N180), 150 kg N ha–1(N150), and 0 kg N ha–1(N0)) and three basal N application stages(seeding(L0), fourleaf stage(L4), and six-leaf stage(L6)) to investigate the effects of reducing the basal N application rate and postponing the basal N fertilization period on grain yield, NUE, and N balance in a soil-wheat system. There was no significant difference in grain yield between the N180 L4 and N240 L0(control) treatments, and the maximum N recovery efficiency and N agronomy efficiency were observed in the N180 L4 treatment. Grain yield and NUE were the highest in the L4 treatment. The leaf area index, flag leaf photosynthesis rate, flag leaf nitrate reductase and glutamine synthase activities, dry matter accumulation, and N uptake post-jointing under N180 L4 did not differ significantly from those under N240 L0. Reduced N application decreased the inorganic N content in the 0–60-cm soil layer, and the inorganic N content of the L6 treatment was higher than those of the L0 and L4 treatments at the same N level. Surplus N was low under the reduced N rates and delayed basal N application treatments. Therefore, postponing and reducing basal N fertilization could maintain a high yield and improve NUE by improving the photosynthetic production capacity, promoting N uptake and assimilation, and reducing surplus N in soil-wheat systems.

关键词： basal nitrogen application stage grain yield nitrogen deficiency nitrogen use efficiency soil nitrogen balance wheat

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A newly proposed heatstroke-induced coagulopathy score in patients with heat illness: A multicenter retrospective study in China

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Chinese Journal of Traumatology 2024年第2期27卷 83-90页

作者： Qing-wei Lin Lin-Cui zhong Long-Ping He Qing-Bo Zeng wei Zhang Qing Song Jing-Chun Song Department of Critical Care Medicine The 908th Hospital of Chinese PLA Logistic Support ForcesNanchang360104Jiangsu ProvinceChina Department of Emergency Medicine The 900th Hospital of Chinese PLA Logistic Support ForcesFuzhou350000China Department of Critical Care Medicine Hainan Hospital of Chinese PLA General HospitalSanya572013Hainan ProvinceChina

Purpose:In patients with heatstroke, disseminated intravascular coagulation (DIC) is associated with greater risk of in-hospital mortality. However, time-consuming assays or a complex diagnostic system may delay immediate treatment. Therefore, the present study proposes a new heatstroke-induced coagulopathy (HIC) score in patients with heat illness as an early warning indicator for DIC.Methods:This retrospective study enrolled patients with heat illness in 24 Chinese hospitals from March 2021 to May 2022. Patients under 18 years old, with a congenital clotting disorder or liver disease, or using anticoagulants were excluded. Data were collected on demographic characteristics, routine blood tests, conventional coagulation assays and biochemical indexes. The risk factors related to coagulation function in heatstroke were identified by regression analysis, and used to construct a scoring system for HIC. The data of patients who met the diagnostic criteria for HIC and International Society on Thrombosis and Haemostasis defined-DIC were analyzed. All statistical analyses were performed using SPSS 26.0.Results:The final analysis included 302 patients with heat illness, of whom 131 (43.4%) suffered from heatstroke, including 7 death (5.3%). Core temperature (OR = 1.681, 95% CI 1.291 - 2.189, p < 0.001), prothrombin time (OR = 1.427, 95% CI 1.175 - 1.733, p < 0.001) and D-dimer (OR = 1.242, 95% CI 1.049 - 1.471, p = 0.012) were independent risk factors for heatstroke, and therefore used to construct an HIC scoring system because of their close relation with abnormal coagulation. A total score ≥ 3 indicated HIC, and HIC scores correlated with the score for International Society of Thrombosis and Hemostasis-DIC (r = 0.8848, p < 0.001). The incidence of HIC (27.5%) was higher than that of DIC (11.2%) in all of 131 heatstroke patients. Meanwhile, the mortality rate of HIC (19.4%) was lower than that of DIC (46.7%). When HIC developed into DIC, parameters of coagulation dysfunction changed significantly: platelet count decrea

关键词： Heat illness Heatstroke Coagulation disorders Diagnosis Disseminated intravascular coagulation

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Addison's disease caused by adrenal tuberculosis may lead to misdiagnosis of major depressive disorder: A case report

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World Journal of Clinical Cases 2024年第1期12卷 217-223页

作者： tian-Xiang Zhang Hong-Yan Xu wei Ma Jian-Bao Zheng Department of Tuberculosis The Tuberculosis Hospital of Shaanxi ProvinceXi’an 710100Shaanxi ProvinceChina Department of General Surgery First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina

BACKGROUND Addison’s disease(AD)is a rare but potentially fatal disease in Western countries,which can easily be misdiagnosed at an early stage.Severe adrenal tuberculosis(TB)may lead to depression in patients.CASE SUMMARY We report a case of primary adrenal insufficiency secondary to adrenal TB with TB in the lungs and skin in a 48-year-old woman.The patient was misdiagnosed with depression because of her depressed mood.She had hyperpigmentation of the skin,nails,mouth,and lips.The final diagnosis was adrenal TB that resulted in the insufficient secretion of adrenocortical hormone.Adrenocortical hormone test,skin biopsy,T cell spot test of TB,and adrenal computed tomography scan were used to confirm the diagnosis.The patient’s condition improved after hormone replacement therapy and TB treatment.CONCLUSION Given the current status of TB in high-burden countries,outpatient doctors should be aware of and pay attention to TB and understand the early symptoms of AD.

关键词： Primary adrenal insufficiency Adrenal tuberculosis Fatigue Hypotension Hyperkalemia Hyponatremia Depression Case report

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Millisecond dynamics of colloidal suspension studied by X-ray photon correlation spectroscopy at the Shanghai Synchrotron Radiation Facility

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Nuclear Science and Techniques 2024年第1期35卷 1-9页

作者： Chen-Hui Cui Zi-Mu Zhou Lin-Feng wei Song-Lin Li Feng tian Xiu-Hong Li Zhi Guo Yi-Hui Xu Huai-Dong Jiang Ren-zhong Tai Shanghai Synchrotron Radiation Facility Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201204China School of Physical Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing 100049China Center for Transformative Science ShanghaiTech UniversityShanghai 201210China

X-ray photon correlation spectroscopy(XPCS)has emerged as a powerful tool for probing the nanoscale dynamics of soft condensed matter and strongly correlated materials owing to its high spatial resolution and penetration capabilities.This technique requires high brilliance and beam coherence,which are not directly available at modern synchrotron beamlines in China.To facilitate future XPCS experiments,we modified the optical setup of the newly commissioned BL10U1 USAXS beamline at the Shanghai Synchrotron Radiation Facility(SSRF).Subsequently,we performed XPCS measurements on silica suspensions in glycerol,which were opaque owing to their high concentrations.Images were collected using a high frame rate area detector.A comprehensive analysis was performed,yielding correlation functions and several key dynamic parameters.All the results were consistent with the theory of Brownian motion and demonstrated the feasibility of XPCS at SSRF.Finally,by carefully optimizing the setup and analyzing the algorithms,we achieved a time resolution of 2 ms,which enabled the characterization of millisecond dynamics in opaque systems.

关键词： XPCS SSRF Silica suspension Glycerol Brownian motion Millisecond dynamics

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A supramolecular self-assembly material based on cucurbituril and cationic TPE as ultra-sensitive probe of energetic pentazolate salts

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Defence Technology（防务技术） 2024年第5期35卷 69-76页

作者： Boan Tang Jingxiang zhong Shutao Wang Shiyu Zhou Yongxing Tang wei Huang School of Chemistry and Chemical Engineering Nanjing University of Science and TechnologyNanjing 210094China

The successful synthesis of the pentazolate anion(cyclo-N-5)has been a great breakthrough in the field of energetic materials.However,the detection methods for these energetic materials based on the pentazolate anion are quite rare.Herein,two fluorescent probes for cyclo-N-5anion were designed.Sensor 1(TPE2N)was synthesized with a tetraphenylethylene functionalized by two cationic groups which can generate strong electrostatic interactions with pentazolate anion and result in specific fluorescent changes.Sensor 2 was designed based on sensor 1 and supramolecular cucurbit[7]uril(CB[7]).The unique structural features of CB[7]provide sites for the interaction between the cations and N-5anion in its cavity,which would generate a platform for the detection and enhance the recognition performance.Isothermal titration calorimetry(ITC)experiment and fluorescence titration experiment indicate the binding molar ratio between sensor 1 with CB[7]is 1:2.Both sensors display typical aggregation-induced emission(AIE)features and good water-solubility.The sensors demonstrate excellent sensitivity to pentazole hydrazine salt with high enhancement constant(sensor 1:1.34×10^(6);sensor 2:3.78×10^(6))and low limit of detection(LOD:sensor 1=4.33μM;sensor 2=1.54μM).The formation of an AIE-based supramolecular sensor effectively improves the sensitivity to N-5anion.In addition,the probes also have good selectivity of N-5anion salts.The research would shed some light on the design of novel fluorescent sensors to detect pentazolate-based molecules and provides an example of supramolecular chemistry combined with fluorescent probes.

关键词： Pentazolate anion Explosives detection Aggregation-induced emission(AIE) Host-guest interaction

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Chemoselective labeling-based spermatozoa glycan imaging reveals abnormal glycosylation in oligoasthenotspermia

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Chinese Chemical Letters 2024年第4期35卷 475-480页

作者： Lijia Xu Tong zhong wei Zhao Bing Yao Lin Ding Huangxian Ju State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China Department of Reproductive Medical Center Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210002China Chemistry and Biomedicine Innovation Center(ChemBIC) Nanjing UniversityNanjing 210023China Center of Clinical Laboratory Science The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210009China

Spermatogenesis, maturation, capacitation and fertilization are precisely regulated by glycosylation. However, the relationship between altered glycosylation patterns and the onset and development of reproductive disorders is unclear, mainly limited by the lack of in situ imaging techniques for spermatozoa glycosylation. We developed an efficient and highly specific spermatozoa glycan imaging technique based on the robust chemoselective labeling of sialic acid(Sia) and N-acetyl-D-galactosamine(Gal/GalNAc). We further proposed a “tandem glycan chemoselective labeling” strategy to achieve simultaneous imaging of two types of glycans on spermatozoa. We applied the developed method to the spermatozoa from oligozoospermic patients and diabetic mice and found that these spermatozoa showed higher levels of Sia and Gal/Gal NAc expression than the normal groups. Moreover, spermatozoa from diabetic mice showed a severe decrease in number, viability, and forward motility, suggesting that in vivo glucose metabolism disorders may lead to an elevated level of spermatozoa glycosylation and have a correlation with the development of oligoasthenotspermia. Our work provides a research tool to reveal the relationship between glycosylation modification and spermatozoa quality, and a promising clue for the development of glycan-based reproductive markers.

关键词： Spermatozoa Glycan Chemoselective labeling Oligoasthenotspermia Fluorescence imaging

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New insights into the deposition of natural gas hydrate on pipeline surfaces:A molecular dynamics simulation study

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Petroleum Science 2024年第1期21卷 694-704页

作者： Jun Zhang Hai-Qiang Fu Mu-Zhi Guo Zhao Wang Li-Wen Li Qi Yin You-Guo Yan wei wei wei-Feng Han Jie zhong School of Materials Science and Engineering China University of Petroleum(East China)Qingdao 266580ShandongChina School of Petroleum Engineering China University of Petroleum(East China)Qingdao 266580ShandongChina Department of Alternative Energy PetroChina Research Institute of Petroleum Exploration&DevelopmentLangfang 065007HebeiChina

Natural gas hydrate(NGH)can cause pipeline blockages during the transportation of oil and gas under high pressures and low temperatures.Reducing hydrate adhesion on pipelines is viewed as an efficient way to prevent NGH blockages.Previous studies suggested the water film can greatly increase hydrate adhesion in gas-dominant system.Herein,by performing the molecular dynamics simulations,we find in water-dominant system,the water film plays different roles in hydrate deposition on Fe and its corrosion surfaces.Specifically,due to the strong affinity of water on Fe surface,the deposited hydrate cannot convert the adsorbed water into hydrate,thus,a water film exists.As water affinities decrease(Fe>Fe_(2)O_(3)>FeO>Fe_(3)O_(4)),adsorbed water would convert to amorphous hydrate on Fe_(2)O_(3)and form the ordered hydrate on FeO and Fe_(3)O_(4)after hydrate deposition.While absorbed water film converts to amorphous or to hydrate,the adhesion strength of hydrate continuously increases(Fe

关键词： Deposition Natural gas hydrate Pipelines Water affinity Adhesion strength

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Genetically modified pigs:Emerging animal models for hereditary hearing loss

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Zoological Research 2024年第2期45卷 284-291页

作者： Xiao Wang tian-Xia Liu Ying Zhang Liang-wei Xu Shuo-Long Yuan A-Long Cui wei-wei Guo Yan-Fang Wang Shi-Ming Yang Jian-Guo Zhao State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Department of Otolaryngology-Head and Neck Surgery Institute of OtolaryngologyChinese PLA General HospitalBeijing 100853China Division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230022China State Key Laboratory of Animal Biotech Breeding Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing100193China

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

关键词： Pigs Animal models Hereditary hearing loss Genetic modification Inner ear

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Uptrend of the Western North Pacific Tropical Cyclone Outflow Height during 1959-2021

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Journal of Meteorological Research 2024年第2期38卷 339-350页

作者： Yuan SUN Zhihao FENG wei zhong Panmao ZHAI Yanluan LIN Shuo LYU College of Advanced Interdisciplinary Studies National University of Defense TechnologyNanjing 211100 College of Meteorology and Oceanography National University of Defense TechnologyChangsha 410073 State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesChina Meteorological AdministrationBeijing 100081 Ministry of Education Key Laboratory for Earth System Modeling Department of Earth System ScienceTsinghua UniversityBeijing 100084

Relatively little is known about the impact of global warming on the tropical cyclone(TC)outflow,despite its large contribution to TC intensity.In this study,based on the International Best Track Archive for Climate Stewardship(IBTrACS)dataset and ERA5 reanalysis data,we show that the TC outflow height has risen significantly(48.20±22.18 m decades-1)in the past decades(1959-2021)over the western North Pacific,and the rising trend tends to be sharper for stronger TCs(the uptrend of severe typhoon is 61.09±40.92 m decades-1).This rising trend of the outflow height explains the contradiction between the decrease trend of the TC outflow temperature and the increase trend of the atmospheric troposphere temperature.Moreover,possible contribution of the TC outflow height uptrend to TC intensity has also been investigated.The results show that the rise of outflow height leads to the decrease of outflow temperature,and thus an increased difference between underlying sea surface temperature(SST)and TC outflow temperature,which eventually favors the increase of TC intensity.

关键词： tropical cyclone outflow height global warming western North Pacific

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