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Microglial Calcium Homeostasis Modulator 2:Novel Anti-neuroinflammation Target for the Treatment of Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第4期40卷 553-556页

作者： yuan Dong Li tang Neuropsychiatry Research Institute The Affiliated Hospital of Qingdao UniversityQingdao UniversityQingdao266000China Qingdao Institute of Measurement Technology Qingdao266000China

Neurodegenerative diseases,including Alzheimer's disease(AD)and Parkinson's disease(PD),are the most common causes of dementia.Current drugs for such diseases can only provide temporary help with the symptoms,leaving the discovery of new drugs urgently in need.Microglial cells are the local immune cells in the nervous system and have been recognized as the key player in neuroinflammation that contributes to the process of neurodegeneration[1],raising the discussion of aiming microglia as the therapeutic target for clinical treatment of neurodegenerative diseases.

关键词： inflammation degenerative drugs

Single Particle Colorimetric Acid Phosphatase Activity Assay with CeO_(2)-modified Gold Nanoparticles

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Chemical Research in Chinese Universities 2024年第2期40卷 320-325页

作者： ZHU tang Jiayao yuan Xiang MAO Guojiang wei Lin XIAO Lehui Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research National and Local Joint Engineering Laboratory for New Petrochemical Materials and Fine Utilization of ResourcesCollege of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha410081P.R.China Henan Key Laboratory of Organic Functional Molecule and Drug Innovation Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine ChemicalsKey Laboratory of Green Chemical Media and ReactionsMinistry of EducationSchool of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiang453007P.R.China College of Chemistry and Chemical Engineering Central South UniversityChangsha410083P.R.China

Acid phosphatase(ACP)is a ubiquitous phosphatase in living organisms.The abnormal variation of ACP is related to various diseases.Herein,we propose a colorimetric method based on CeO_(2)-modified gold core shell nanoparticles(Au@CeO_(2)NPs)to analyze ACP activity with high sensitivity and specificity.In this design,2-phospho-L-ascorbic acid trisodium salt(AAP)is dephosphorylated by ACP and produces reductive ascorbic acid(AA),which makes the CeO_(2)shell decomposition.A remarkable blue shift of localized surface plasmon resonance peak(LSPR,from yellow to green)along with the scattering intensity ratio changes from individual Au@CeO_(2)NPs are observed.ACP activity can be quantified by calculating the ratio changes of individual Au@CeO_(2)NPs.This assay reveals limit of detection(LOD)of 0.044 mU/mL and the linear range of 0.05–5.0 mU/mL,which are much lower than most of spectroscopic measurements in bulk solution.Furthermore,the recovery measurements in real samples are satisfactory and the capacity for practical application is demonstrated.As a consequence,Au@CeO_(2)NPs used in this assay will find new applications for the ultrasensitive detection of enzyme activity.

关键词： Single particle imaging Dark field Gold nanoparticle Enzyme activity Colorimetric detection

Pathogen-induced methylglyoxal negatively regulates rice bacterial blight resistance by inhibiting OsCDR1 protease activity

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Molecular Plant 2024年第2期17卷 325-341页

作者： Zheng-wei Fu Jian-Hui Li Xiang Gao Shi-Jia Wang Ting-Ting yuan Ying-tang Lu State Key Laboratory of Hybrid Rice College of Life SciencesRenmin Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China Key Laboratory of Biology and Genetic Improvement of OilCrops Ministry of Agriculture and Rural AffairsOilCrops Research Institute of the Chinese Academy of Agricultural SciencesWuhan 430062China

Xanthomonas oryzae pv.oryzae(Xoo)causes bacterial blight(BB),a globally devastating disease of rice(Oryza sativa)that is responsible for significant crop loss.Sugars and sugar metabolites are important for pathogen infection,providing energy and regulating events associated with defense responses;howev-er,the mechanisms by which they regulate such events in BB are unclear.As an inevitable sugar metabolite,methylglyoxal(MG)is involved in plant growth and responses to various abiotic stresses,but the underlying mechanisms remain enigmatic.Whether and how MG functions in plant biotic stress responses is almost completely unknown.Here,we report that the Xoo strain PXO99 induces OsWRKY62.1 to repress transcrip-tion of OsGLY Il genes by directly binding to their promoters,resulting in overaccumulation of MG.MG negatively regulates rice resistance against Pxo99:osglyll2 mutants with higher MG levels are more sus-ceptible to the pathogen,whereas OsGLYIl2-overexpressing plants with lower MG content show greater resistance than the wild type.Overexpression of OsGLYll2 to prevent excessive MG accumulation confers broad-spectrum resistance against the biotrophic bacterial pathogens Xoo and Xanthomonas oryzae pv.oryzicola and the necrotrophic fungal pathogen Rhizoctonia solani,which causes rice sheath blight.Further evidence shows that MG reduces rice resistance against PXO99 through CONSTITUTIVE DISEASE RESISTANCE 1(OsCDR1).MGmodifies the Arg97 residue of OsCDR1to inhibit its aspartic protease activ-ity,which is essential for OsCDR1-enhanced immunity.Taken together,these findings illustrate how Xoo promotes infection by hijacking a sugar metabolite in the host plant.

关键词： Oryza sativa bacterial blight OsWRKY62.1 methylglyoxal OsCDR1

Removal of pathogenic indicator microorganisms during partial nitrification:the role of free nitrous acid

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 93-102页

作者： Jiaojiao Xu Xiaotian Chen Rui tang Jingwei Feng Shoujun yuan wei Wang Zhen-Hu Hu Anhui Engineering Laboratory of Rural Water Environment and Resource School of Civil EngineeringHefei University of TechnologyHefei 230009China Hefei 168 High School Hefei 230025China Shanghai Key Laboratory of Materials Protection and Advanced Materials in Electric Power Shanghai University of Electric PowerShanghai 200090China

Digested wastewater contains pathogenic microorganisms and high ammonia concentrations,which can pose a potential risk to public health.Effective removal of pathogens and nitrogen is crucial for the post-treatment of digested wastewater.Partial nitrification-anammox is an energy-saving nitrogen removal process.Free nitrous acid(FNA),an intermediate product of partial nitrification,has the potential to inactivate microorganisms.However,the efficiency and mechanisms of FNA-related inactivation in pathogens during partial nitrification remains unclear.In this study,Enterococcus and Escherichia coli(E.coli)were selected to investigate the efficiency and mechanisms of FNA-related inactivation in partial nitrification process.The results revealed that 83%±13%and 59%±27%of E.coli and Enterococcus were removed,respectively,in partial nitrification process at FNA concentrations of 0.023−0.028 mg/L.When the concentration of FNA increased from 0 to 0.5 mg/L,the inactivation efficiencies of E.coli and Enterococcus increased from 0 to 99.9%and 89.9%,respectively.Enterococcus exhibited a higher resistance to FNA attack compared to E.coli.3D-laser scanning microscopy(3D-LSM)and scanning electron microscopy(SEM)revealed that FNA exposure caused the surface collapse of E.coli and Enterococcus,as well as visible pore formation on the surface of E.coli cells.4',6-Diamidino-2-phenylindole dihydrochloride n-hydrate(DAPI)/propidium iodide(PI)and biomolecule leakage confirmed that inactivation of E.coli and Enterococcus occurred due to breakdown of cell walls and cell membranes.These findings indicate that partial nitrification process can be used for the removal of residual pathogenic microorganisms.

关键词： Partial nitrification Free nitrous acid Pathogenic indicator microorganism Inactivation Cell structure

Effects of extracellular vesicle-derived noncoding RNAs on pre-metastatic niche and tumor progression

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Genes & Diseases 2024年第1期11卷 176-188页

作者： Zhuang Chen Qiming Wang Jinbo Liu Wenkang Wang weitang yuan Yang Liu Zhenqiang Sun Chengzeng Wang Department of Colorectal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan 450001China Department of Internal Medicine Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenan 450008China Department of Breast Surgery The First Affliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Radiotherapy Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouHenan 450008China The First Affiliated Hospital of Zhengzhou University ZhengzhouHenan 450052China

A pre-metastatic niche(PMN)is a protective microenvironment that facilitates the colonization of disseminating tumor cells in future metastatic organs.Extracellular vesicles(EVs)play a role in intercellular communication by delivering cargoes,such as noncoding RNAs(ncRNAs).The pivotal role of extracellular vesicle-derived noncoding RNAs(EV-ncRNAs)in the PMN has attracted increasing attention.In this review,we summarized the effects of EV-ncRNAs on the PMN in terms of immunosuppression,vascular permeability and angiogenesis,inflammation,metabolic reprogramming,and fibroblast alterations.In particular,we provided a comprehensive overview of the effects of EV-ncRNAs on the PMN in different cancers.Finally,we discussed the promising clinical applications of EV-ncRNAs,including their potential as diagnostic and prognostic markers and therapeutic targets.

关键词： Biomarker Extracellular vesicles Noncoding RNAs

Understanding the rapid spread of antimicrobial resistance genes mediated by Is26

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mLife 2024年第1期3卷 101-109页

作者： Na tang Dawei wei yuan Zeng Gang Zhang Chao Wang Jie Feng Yuqin Song State Key Laboratory of Microbial Resources Institute of MicrobiologyChinese Academy of SciencesBejingChina College of Life Science University of Chinese Academy of SciencesBeijingChina

Insertion sequences(ISs)promote the transmission of antimicrobial resistance genes(ARGs)across bacterial populations.However,their contributions and dynamics during the transmission of resistance remain unclear.In this study,we selected is26 as a representative transposable element to decipher the relationship between ISs and ARGs and to investigate their transfer features and transmission trends.We retrieved 2656 translocatable IS26-bounded units with ARGs(tiS26-bUs-ARGs)in complete bacterial genomes from the NCBI RefSeq database.In total,124 ARGs spanning 12 classes of antibiotics were detected,and the average contribution rate of IS26 to these genes was 41.2%.We found that IS26-bounded units(IS26-bUs)mediated extensive ARG dissemination within the bacteria of the Gammaproteobacteria class,showing strong transfer po-tential between strains,species,and even phyla.The Is26-bUs expanded in bacterial populations over time,and their temporal expansion trend was significantly correlated with antibiotic usage.This wide dissemination could be due to the nonspecific target site preference of is26.Finally,we experimentally confirmed that the introduction of a single copy of is26 could lead to the formation of a composite transposon mediating the transmission of“passenger”genes.These observations extend our knowledge of the Is26 and provide new insights into the mediating role of ISs in the dissemination of antibiotic resistance.

关键词： antibiotic consumption antibiotic resistance genes horizontal gene transfer insertion sequence Is26

Hydrodynamic characteristics and particle tracking of 90° lateral intakes at an inclined river slope

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Water Science and Engineering 2024年第2期17卷 197-208页

作者： wei He Si-yuan Feng Jian Zhang Hong-wu tang Yang Xiao Sheng Chen Chun-sheng Liu College of Water Conservancy and Hydropower Engineering Hohai UniversityNanjing 210098China State Key Laboratory of Hydrology Water Resources and Hydraulic Engineering Hohai UniversityNanjing 210098China Collaborative Innovation Center on Water Safety and Water Science Hohai UniversityNanjing 210098China

Lateral intakes are common in rivers.The pump effciency and sediment deposition are determined by the local hydrodynamic characteristics and mainstream division width.The hydraulic characteristics of lateral withdrawal from inclined river slopes at different intake elevations should be investigated.Meanwhile,the division width exhibits significant vertical non-uniformity at an inclined river slope,which should be clarified.Hence,a three-dimensional(3-D)hydrodynamic and particle-tracking model was developed with the Open Source Field Operation and Manipulation(Open FOAM),and the model was validated with physical model tests for 90°lateral withdrawal from an inclined side bank.The flow fields,withdrawal sources,and division widths were investigated with different intake bottom elevations,withdrawal discharges,and main channel velocities.This study showed that under inclined side bank conditions,water entered the intake at an oblique angle,causing significant 3-D spiral flows in the intake rather than two-dimensional closed recirculation.A lower withdrawal discharge,a lower bottom elevation of the intake,or a higher main channel velocity could further strengthen this phenomenon.The average division width and turbulent kinetic energy were smaller under inclined side bank conditions than under vertical bank conditions.With a low intake bottom elevation,a low withdrawal discharge,or a high main channel velocity,the sources of lateral withdrawal were in similar ranges near the local inclined bank in the vertical direction.Under inclined slope conditions,sediment deposition near the intake entrance could be reduced,compared to that under vertical slope conditions.The results provide hydrodynamic and sediment references for engineering designs for natural rivers with inclined terrains.

关键词： Lateral withdrawal Hydrodynamic characteristics Particle tracking Inclined river slope Bottom elevation of intake OpenFOAM

Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1344-1360页

作者： Chun-yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-wei tang Qiu-Lu Zhang Ling-Fu Zhang Jian-yuan Luo Department of Pathology Institute of Systems BiomedicineSchool of Basic Medical Sciences Peking UniversityPeking University Third HospitalPeking University Health Science CenterBeijing 100191China Department of General Surgery Peking University Third HospitalBeijing 100191China Department of Medical Genetics Department of Biochemistry and BiophysicsSchool of Basic Medical Sciences Peking UniversityPeking University Health Science CenterBeijing 100191China

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin overexpression.MUC1 has been identified as a critical oncogene in the progression of CCA.However,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete.AIM To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients.METHODS Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic analyses.Subse-quent validations were conducted through spatial transcriptomics and immuno-histochemistry.The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data types.RESULTS CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness.MUC5AC-high cells were found to promote CCA progression through WNT signaling.MUC5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral treatments.MUC13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor immunity.MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils.Utilizing the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple cohorts.CCA samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer prognosis.CONCLUSION Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关键词： Mucin Cholangiocarcinoma Single-cell RNA sequencing Spatial transcriptomics Prognosis

Global trends in diabetic eye disease research from 2012 to 2021

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Neural Regeneration Research 2024年第10期19卷 2310-2320页

作者： yuan yuan Shangli Ji Yali Song Zhaodi Che Lu Xiao Shibo tang Jia Xiao Aier School of Ophthalmology Central South UniversityChangshaHunan ProvinceChina Changsha Aier Eye Hospital ChangshaHunan ProvinceChina Aier Eye Institute ChangshaHunan ProvinceChina Department of Metabolic and Bariatric Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

关键词： clinical trials diabetic cataracts diabetic eye disease diabetic glaucoma diabetic macular edema diabetic retinopathy drug development global research publication research grant