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Rapid and chemoselective imidation of sulfides in aqueous buffer enabled by a novel guanidine-derived N-O reagent

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Science China Chemistry 2024年第6期67卷 1929-1934页

作者： Hanzheng Li Long Xu Jiajia Dong Key laboratory of Organofluorine Chemistry Center for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200032China Institute of translational Medicine National Facility for Translational Medicine(Shanghai)Shanghai Jiao Tong UniversityShanghai200240China School of Chemistry and Chemical Engineering Zhangjiang Institute for Advanced StudyShanghai Jiao Tong UniversityShanghai200240China Shanghai Artificial Intelligence laboratory Shanghai200232China

Herein we report the facile synthesis of a series of novel N-O reagents and identify N′-di-Boc-N′′-[(mesitylsulfonyl)oxy]-guanidine as an efficient imidating *** reagent is synthetically scalable and bench-stable,yet it shows unprecedented reactivity and chemoselectivity towards S(II)in buffer/hexafluoroisopropanol(HFIP)system,to generate a new class of Nguanyl *** transformation of N-guanyl sulfilimines to N-guanyl sulfoximines provides us a chance to investigate these rarely reached compounds,which are shown to be versatile precursors to a variety of N-heterocyclic and *** work provides an addition to the tool box of both sulfur imidation and guanidine synthesis,especially for the need of rapid and selective modifications of sulfur(II)center under biocompatible conditions.

关键词： sulfur imidation N-O reagent

D-band center coordination modulated enzyme-like activity in Fe-Cu dual-metal single-atom nanozymes

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Nano research 2024年第7期17卷 5872-5883页

作者： Ling Liu Shaofang Zhang Guo Li Yadong Zhe Jiamin Liu Xinxu Zhang Jiahao Wei Xin Sun Yonghui Li Xiao-Dong Zhang Tianjin Key laboratory of Brain Science and Neural Engineering Academy of Medical Engineering and Translational MedicineTianjin UniversityTianjin 300072China Department of Physics and Tianjin Key laboratory of Low Dimensional Materials Physics and Preparing Technology School of SciencesTianjin UniversityTianjin 300350China

After explorations in a diversity of single-atom nanozymes(SAzymes),developing dual-centered SAzymes becomes a promising approach for superior catalytic *** confusing mechanisms including atomic coordination,spatial configuration,and metal–metal atom interaction hinder the development and design of ***,a dual-centered Fe-Cu-N_(x)SAzyme exhibits excellent peroxidase(POD)-and catalase(CAT)-like activities with d-band center(ε_(d))coordination of Fe and Cu in multiple reaction stages,which plays a critical role in the adsorption of H_(2)O_(2)molecule and H_(2)O and O_(2)***,the dband center coordination,which can be represented byε_(d)(Fe)–ε_(d)(Cu)shifts,leads to the competition between one-side and bilateral adsorption,which determines the favorable reaction path with lower energy *** on experimental statistics,simulated formation energies,and reaction barriers,3 configurations,Fe-Cu-N6-I,Fe-Cu-N_(8)-II,and Fe-Cu-N_(8)-III,are modeled and ***,configuration-dependent catalytic selectivity and the competition between one-side and bilateral adsorption can be unveiled by d-band center coordination paradigm *** simulations suggest that the unsymmetrical charge distribution over the three Fe-Cu configurations could tune the adsorption strength compared with the counterparts FeN_(4)and CuN_(4).The present work provides a potential route for optimizing enzyme-like catalysis by designing the dual-or even triple-metal SAzymes,which demonstrates the large space to modulate the metal atomic configuration and interaction.

关键词： single-atom catalysis Fe-Cu dual-metal d-band center coordination enzyme mimicking competitive adsorption mechanisms

Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

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Neural Regeneration research 2024年第3期19卷 629-635页

作者： Jingzhou Liu Xin Xin Jiejie Sun Yueyue Fan Xun Zhou Wei Gong Meiyan Yang Zhiping Li Yuli Wang Yang Yang Chunsheng Gao State Key laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijingChina Academy of Medical Engineering and translational Medicine Medical CollegeTianjin UniversityTianjinChina

Traumatic brain injury results in neuronal loss and glial scar *** neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain *** reprogramming is a promising strategy to convert glial scars to neural ***,previous studies have reported inconsistent *** this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target *** results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive ***,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain *** summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

关键词： AAV9P1 astrocytes astrocyte-to-neuron conversion GFAP promoter glial scar induced neurons neuronal reprogramming P1 peptide PTBP1 traumatic brain injury

Progress on early diagnosing Alzheimer’s disease

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Frontiers of Medicine 2024年第3期18卷 446-464页

作者： Yixin Chen Murad Al-Nusaif Song Li Xiang Tan Huijia Yang Huaibin Cai Weidong Le Liaoning Provincial Key laboratory for research on the Pathogenic Mechanisms of Neurological Diseases The First Affiliated Hospital of Dalian Medical UniversityDalian116021China Transgenic Section Laboratory of NeurogeneticsNational Institute on AgingNational Institutes of HealthBethesdaMD20892USA Institute of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChinese Academy of Sciences Sichuan Translational Medicine Research HospitalChengdu610072China

Alzheimer’s disease(AD)is a progressive neurodegenerative disorder that affects both cognition and non-cognition *** disease follows a continuum,starting with preclinical stages,progressing to mild cognitive and behavioral impairment,ultimately leading to *** detection of AD is crucial for better diagnosis and more effective ***,the current AD diagnostic tests of biomarkers using cerebrospinal fluid and/or brain imaging are invasive or expensive,and mostly are still not able to detect early disease ***,there is an urgent need to develop new diagnostic techniques with higher sensitivity and specificity during the preclinical stages of *** non-cognitive manifestations,including behavioral abnormalities,sleep disturbances,sensory dysfunctions,and physical changes,have been observed in the preclinical AD stage before occurrence of notable cognitive *** research advances have identified several biofluid biomarkers as early indicators of *** review focuses on these non-cognitive changes and newly discovered biomarkers in AD,specifically addressing the preclinical stages of the ***,it is of importance to explore the potential for developing a predictive system or network to forecast disease onset and progression at the early stage of AD.

关键词： Alzheimer’s disease early diagnosis non-cognitive symptoms biomarkers

Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia

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Frontiers of Medicine 2024年第2期18卷 327-343页

作者： Niu Qiao Yizhu Lyu Feng Liu Yuliang Zhang Xiaolin Ma Xiaojing Lin Junyu Wang Yinyin Xie Ruihong Zhang Jing Qiao Hongming Zhu Li Chen Hai Fang Tong Yin Zhu Chen Qiang Tian Saijuan Chen Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Second Hospital of Dalian Medical UniversityDalian116021China

The treatment of PML/RARA+acute promyelocytic leukemia(APL)with all-trans-retinoic acid and arsenic trioxide(ATRA/ATO)has been recognized as a model for translational medicine *** an altered microenvironment is a general cancer hallmark,how APL blasts shape their plasma composition is poorly ***,we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters,proteomes,and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction *** study revealed the two prominent features of the APL plasma,suggesting a possible involvement of APL blasts in modulating plasma *** was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts,and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/***,results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage,which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular ***,our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia plasma proteomics plasma metabolomics cross-sectional correlation network pathogenesis treatment

The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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research 2024年第2期2023卷 373-387页

作者： Di Wu Yi Sun Cancer Institute(Key laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical research Center for Cancer Zhejang ProvinceChina Key laboratory of Molecular Biology in Medical Sciences Zhejang ProvinceChina research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

Harnessing cytokine-induced killer cells to accelerate diabetic wound healing:an approach to regulating post-traumatic inflammation

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Regenerative Biomaterials 2024年第2期3卷 88-99页

作者： Yixi Yang Cheng Zhang Yuan Jiang Yijun He iawei Cai Lin Liang Zhaohuan Chen Sicheng Pan Chu Hua Keke Wu Le Wang Zhiyong Zhang translational research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University Guangdong Province Engineering Research Center for Biomedical EngineeringState Key Laboratory of Respiratory DiseaseDepartment of Orthopaedic SurgeryMedical Technology and Related Equipment Research for Spinal Injury TreatmentCity Key LaboratoryThe Third Affliated Hospital of Guangzhou Medical UniversitySchool of Biomedical EngineeringGuangzhou MedicalUniversityGuangzhouGuangdong510150P.R.China Department of Osteoarthropathy and Sports Medicine Panyu Central HospitalGuangzhou 511400P.R.China

Impaired immunohomeostasis in diabetic wounds prolongs infiammation and cytokine dysfunction,thus,delaying or pre-venting wound-surface *** clinical studies have been conducted on cytokine-induced killer(CIK)cells recently,as they can be easily proliferated using a straightforward,inex-pensive ***,the function of CIK cells in regulat-ing inflammatory environments has been drawing attention for clinical *** the current investigation,we discovered the regenerative capacity of these cells in the chal-lenging environment of wounds that heal poorly due to *** demonstrated that the intravenous injection of CIK cells can re-establish a proregenerative inflammatory *** *** accelerateskin healing in diabetic *** results indicated that CIK cell treatment affects macrophage polarization and restores the function regenerative cells under hyperglycemic *** novel cellular therapy offers a promising intervention for clinical applic tions through specific inflammatory regulation functions.

关键词： macrophage diabetic wound post-traumatic inflammation cytokine-induced killer cells vascularization

Lipidomic remodeling during mammalian preimplantation embryonic development

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Life Metabolism 2024年第2期3卷 3-5页

作者： Qingran Kong Shaorong Gao Zhejiang Provincial Key laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouZhejiang 325035China Clinical and translational research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

The dynamic changes in lipids during early embryonic development in mammals have not yet been comprehensively investi*** a recent paper published in Nature Cell Biology,Zhang et *** the dynamic lipid landscapes during preimplantation embryonic development in mice and *** highlight the crucial role of lipid unsaturation in regulating embryogenesis.

关键词： Lipid al. lipids

Broadening environmental research in the era of accurate protein structure determination and predictions

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Frontiers of Environmental Science & Engineering 2024年第7期18卷 169-178页

作者： Mingda Zhou Tong Wang Ke Xu Han Wang Zibin Li Wei-xian Zhang Yayi Wang State Key laboratory of Pollution Control and Resources Reuse Shanghai Institute of Pollution Control and Ecological SecurityCollege of Environmental Science and EngineeringTongji UniversityShanghai 200092China translational research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People's HospitalSchool of MedicineTongji UniversityShanghai 200434China

The deep-learning protein structure prediction method AlphaFold2 has garnered enormous attention beyond the realm of structural biology,for its groundbreaking contribution to solving the"protein foiding problem"In this perspective,we explore the connection between protein structure studies and environmental research,delving into the potential for addressing specific environmental *** are promising for environmental applications because of the functional diversity endowed by their structural ***,structural studies on proteins with environmental significance remain ***,we present the opportunity to study proteins by advancing experimental determination and deep-learning prediction ***,the latest progress in environmental research via cryogenic electron microscopy is *** allows us to determine the structure of protein complexes in their native state within cells at molecular resolution,revealing environmentally-associated structural *** the remarkable advancements in computational power and experimental resolution,the study of protein structure and dynamics has reached unprecedented depth and *** advancements will undoubtedly accelerate the establishment of comprehensive environmental protein structural and functional *** opportunities for protein engineering exist to enable innovative solutions for environmental applications,such as the degradation of persistent contaminants,and the recovery of valuable metals as well as rare earth elements.

关键词： Environmental proteins Protein structure Cryogenic electron microscopy Protein structure prediction Protein engineering Artificial Intelligence