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Science China Chemistry 2024年第3期67卷 953-962页

作者： Yuan-Qing Gu Hong-Xin Long Dan-Dan Zhang Mei-Feng Ruan Guo-Kai Liu school of Pharmacy Shenzhen University Medical SchoolShenzhen UniversityShenzhen 518055China

Development of practical and versatile electrophilic difluoromethylating reagent is still a grand challenge so far due to its inherent instability or low ***,we report the design and synthesis of difluoromethyl phenoxathiinium tetrafluoroborate(PT-CF_(2)H^(+)BF_(4)^(-)) as a novel difluoromethylating reagent,which proves to be a bench-stable,general,powerful and versatile reagent with divergent·CF_(2)H,CF_(2)H^(+),and:CF_(2) *** use of this reagent,we demonstrated a vast array of difluoromethyl radical transfer reactions via diverse pathways involving photocatalyst-free visible-light induction,visible-light photoredox catalysis and visible-light mediation single electron transfer of EDA ***,the green and highly effective CF_(2)H^(+) and:CF_(2) transfer reactions were also readily accomplished.

关键词： difluoromethyl phenoxathiinium salt versatile difluoromethylating reagent difluoromethyl radical difluoromthyl cation difluorocarbene

Search for an exotic vectorlike X-quark in same-sign dilepton final states at the future 3 TeV CLIC

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Chinese Physics C 2024年第7期48卷 67-74页

作者：张艳菊常金龙刘太刚 school of medical Engineering Xinxiang Medical UniversityXinxiang 453003China

Vectorlike quarks(VLQs)with masses at the TeV-scale have been predicted in many new physics scenarios beyond the Standard Model(SM).Based on a simplified(X,T)doublet model including the exotic vectorlike X quark(VLQ-X)with an electric charge 5/3,we study the production of the VLQ-X decaying into tW at the future Compact Linear Collider(CLIC)with √s=3 TeV including the initial state radiation and beamstrahlung *** focus on the final signals,including same-sign dileptons(electrons or muons),at least one b-tagged jet,and large missing transverse *** performing detailed signal-to-background analyses and detector simulations,we obtain the 2σexclusion capabilities and discovery reaches,respectively,on the mass of the VLQ-Xmx as well as the relevant parameters(Br(X→_(t)W))for mx≥1500GeV and the coupling strength g^(*) for mx≥1500 GeV)for some typical luminosities at the 3 TeV CLIC.

关键词： Vectorlike quarks CLIC same-sign dilepton

Clinical implications of single cell sequencing for bladder cancer

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Oncology Research 2024年第4期32卷 597-605页

作者： REZA YADOLLAHVANDMIANDOAB MEHRSA JALALIZADEH FRANCIELE APARECIDA VECHIA DIONATO KEINI BUOSI PATRÍCIA A.F.LEME LUCIANA S.B.DAL COL CRISTIANE F.GIACOMELLI ALEX DIAS ASSIS NASIM BASHIRICHELKASARI LEONARDO OLIVEIRA REIS UroScience School of Medical SciencesUniversity of CampinasUNICAMPCampinasSao Paulo13083-872Brazil ImmunOncology Pontifical Catholic University of CampinasPUC-CampinasCampinasSao Paulo13087-571Brazil

Bladder cancer(BC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per *** this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA *** searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February *** included original studies that used at least one single-cell technology to study bladder ***-one publications were included in the ***-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition *** studies were able to diagnose BC by identifying neoplastic cells through single-cell sequencing urine *** remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell ***-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer *** nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.

关键词： Bladder cancer Urothelial carcinoma Transitional cell carcinoma Single-cell sequencing Tumor heterogeneity Immunotherapy Scoping review Tumor microenvironment

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-*** addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

Impact of scandium and terbium on the mechanical properties,corrosion behavior,and biocompatibility of biodegradable Mg-Zn-Zr-Mn alloys

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Journal of Magnesium and Alloys 2024年第2期12卷 546-572页

作者： Khurram Munir Jixing Lin Xian Tong Arne Biesiekierski Yuncang Li Cuie Wen school of Engineering RMIT UniversityMelbourneVictoria 3001Australia school and Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325027China

Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone *** earth elements(REEs)have demonstrated their effectiveness in tailoring the corrosion and mechanical behavior of Mg *** study methodically investigated the impacts of scandium(Sc)and terbium(Tb)in tailoring the corrosion resistance,mechanical properties,and biocompatibility of Mg–0.5Zn–0.35Zr–0.15Mn(MZZM)alloys fabricated via casting and hot *** indicate that addition of Sc and Tb improved the strength of MZZM alloys via grain size reduction and solid solution strengthening *** extruded MZZM–(1–2)Sc–(1–2)Tb(wt.%)alloys exhibit compressive strengths within the range of 336–405 MPa,surpassing the minimum required strength of 200 MPa for bone implants by a significant *** polarization tests revealed low corrosion rates of as–cast MZZM(0.25 mm/y),MZZM–2Tb(0.45 mm/y),MZZM–1Sc–1Tb(0.18 mm/y),and MZZM–1Sc–2Tb(0.64 mm/y),and extruded MZZM(0.17 mm/y),MZZM–1Sc(0.15 mm/y),MZZM-2Sc(0.45 mm/y),MZZM-1Tb(0.17 mm/y),MZZM-2Tb(0.10 mm/y),MZZM–1Sc-1Tb(0.14 mm/y),MZZM-1Sc-2Tb(0.40 mm/y),and MZZM–2Sc–2Tb(0.51 mm/y)alloys,which were found lower compared to corrosion rate of high-purity Mg(~1.0 mm/y)reported in the ***,addition of Sc,or Tb,or Sc and Tb to MZZM alloys did not adversely affect the viability of SaOS2 cells,but enhanced their initial cell attachment,proliferation,and spreading shown via polygonal shapes and *** study emphasizes the benefits of incorporating Sc and Tb elements in MZZM alloys,as they effectively enhance corrosion resistance,mechanical properties,and biocompatibility simultaneously.

关键词： Corrosion property In vitro cytotoxicity Magnesium alloys Mechanical property Rare earth elements

Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An Department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell *** review summarizes the existing scRNA-seq technologies together with their strengths and *** applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune ***-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

Reperfusion and cytoprotective agents are a mutually beneficial pair in ischaemic stroke therapy:an overview of pathophysiology,pharmacological targets and candidate drugs focusing on excitotoxicity and free radical

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Stroke & Vascular Neurology 2024年第4期9卷 351-359页

作者： Xiumei Xu Mingyu Chen Dongya Zhu school of Pharmacy Nanjing Medical UniversityNanjingJiangsuChina

Stroke is the second-leading cause of death and the leading cause of disability in much of the *** particular,China faces the greatest challenge from stroke,since the population is aged *** decades of clinical trials,no neuroprotectant has had reproducible efficacy on primary clinical end points,because reperfusion is probably a necessity for neuroprotection to be clinically ***,the success of thrombolysis and endovascular thrombectomy has taken us into a reperfusion era of acute ischaemic stroke(AIS)*** cytoprotective agents can prevent detrimental effects of ischaemia,and therefore‘freeze’ischaemic penumbra before reperfusion,extend the time window for reperfusion *** reperfusion often leads to reperfusion injury,including haemorrhagic transformation,brain oedema,infarct progression and neurological worsening,cytoprotective agents will enhance the efficacy and safety of reperfusion therapy by preventing or reducing reperfusion ***,reperfusion and cytoprotective agents are a mutually beneficial pair in AIS *** this review,we outline critical pathophysiological events causing cell death within the penumbra after ischaemia or ischaemia/reperfusion in the acute phase of AIS,focusing on excitotoxicity and free *** discuss key pharmacological targets for cytoprotective therapy and evaluate the recent advances of cytoprotective agents going through clinical trials,highlighting multitarget cytoprotective agents that intervene at multiple levels of the ischaemic and reperfusion cascade.

关键词： protective injuries drugs

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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Oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO KIM UIJU CHO SOOK HEE HONG HYUNG SOON PARK IN-HO KIM HO JUNG AN BYOUNG YONG SHIM JIN HYOUNG KANG Division of medical Oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Department of Pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Division of medical Oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)*** cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival ***,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing ***:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with *** APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot *** blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B *** viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with ***:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with *** with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B *** treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B *** to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B ***:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR *** result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of Oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu Li Huang Dali Zheng Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian Key Laboratory of Oral Diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Preventive Dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor *** findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis

Visualizing Wallerian degeneration in the corticospinal tract after sensorimotor cortex ischemia in mice

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Neural Regeneration Research 2024年第3期19卷 636-641页

作者： Jiao Mu Liufang Hao Zijue Wang Xuyang Fu Yusen Li Fei Hao Hongmei Duan Zhaoyang Yang Xiaoguang Li Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stroke can cause Wallerian degeneration in regions outside of the brain,particularly in the corticospinal *** investigate the fate of major glial cells and axons within affected areas of the corticospinal tract following stroke,we induced photochemical infarction of the sensorimotor cortex leading to Wallerian degeneration along the full extent of the corticospinal *** first used a routine,sensitive marker of axonal injury,amyloid precursor protein,to examine Wallerian degeneration of the corticospinal *** antibody to amyloid precursor protein mapped exclusively to proximal axonal segments within the ischemic cortex,with no positive signal in distal parts of the corticospinal tract,at all time *** improve visualization of Wallerian degeneration,we next utilized an orthograde virus that expresses green fluorescent protein to label the corticospinal tract and then quantitatively evaluated green fluorescent protein-expressing *** this approach,we found that axonal degeneration began on day 3 post-stroke and was almost complete by 7 days after *** addition,microglia mobilized and activated early,from day 7 after stroke,but did not maintain a phagocytic state over ***,astrocytes showed relatively delayed mobilization and a moderate response to Wallerian ***,no anterograde degeneration of spinal anterior horn cells was observed in response to Wallerian degeneration of the corticospinal *** conclusion,our data provide evidence for dynamic,pathogenic spatiotemporal changes in major cellular components of the corticospinal tract during Wallerian degeneration.

关键词： corticospinal tract green fluorescent protein microglia spinal anterior horn cells stroke virus trace Wallerian degeneration