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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea department of Immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka present address:Immunology and microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B cells.Adoptive transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B cells.In summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA present address:University of Colorado Boulder BoulderCO 80309USA present address:Dana Farber Cancer Institute BostonMA 02215USA present address:Massachusetts Institute of Technology BostonMA 02139USA present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

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Modular Synthesis of Multi-substituted Cyclobutanones Enabled by Oxyallyl Cations

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Chinese Journal of Chemistry 2024年第5期42卷 459-463页

作者： Meng Wang Zhonggui Wang Ping Lu Research Center for Molecular Recognition and Synthesis Department of ChemistryFudan University220 Handan LuShanghai200433 China present address: department of Cancer Biology Dana-Farber Cancer Institute department of Biological Chemistry and Molecular Pharmacology Harvard Medical SchoolBostonMA 02115USA

Stereoselective synthesis of multi-substituted cyclobutanes with different substituents is still a daunting challenge in organic synthesis.We report here a practical and facile approach to synthesizing all-trans 2,3,4-trisubstituted cyclobutanones from readily available dichlorocyclobutanones.The substitution reaction proceeds smoothly via oxyallyl cation intermediates under mild basic conditions.Further transformation to the synthesis of 1,2,3,4-tetrasubstituted cyclobutanes was also explored.

关键词： Diastereoselectivity Modular synthesis Nucleophilic substitution Organohalides Oxyallyl cation Precision functionalization Strained molecules 1,2,3,4-Tetrasubstituted cyclobutanes

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Trend of Developing Aqueous Liquid and Gel Electrolytes for Sustainable,Safe,and High‑Performance Li‑Ion Batteries

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Nano-Micro Letters 2024年第1期16卷 17-34页

作者： Donghwan Ji Jaeyun Kim School of Chemical Engineering Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences&Technology(SAIHST)Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Biomedical Institute for Convergence at SKKU(BICS) Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Institute of Quantum Biophysics(IQB) Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea present address:department of NanoEngineering University of California San DiegoLa JollaSan DiegoCA 92093USA

Current lithium-ion batteries(LIBs)rely on organic liquid electrolytes that pose significant risks due to their flammability and toxicity.The potential for environmental pollution and explosions resulting from battery damage or fracture is a critical concern.Water-based(aqueous)electrolytes have been receiving attention as an alternative to organic electrolytes.However,a narrow electrochemicalstability window,water decomposition,and the consequent low battery operating voltage and energy density hinder the practical use of aqueous electrolytes.Therefore,developing novel aqueous electrolytes for sustainable,safe,high-performance LIBs remains challenging.This Review first commences by summarizing the roles and requirements of electrolytes–separators and then delineates the progression of aqueous electrolytes for LIBs,encompassing aqueous liquid and gel electrolyte development trends along with detailed principles of the electrolytes.These aqueous electrolytes are progressed based on strategies using superconcentrated salts,concentrated diluents,polymer additives,polymer networks,and artificial passivation layers,which are used for suppressing water decomposition and widening the electrochemical stability window of water of the electrolytes.In addition,this Review discusses potential strategies for the implementation of aqueous Li-metal batteries with improved electrolyte–electrode interfaces.A comprehensive understanding of each strategy in the aqueous system will assist in the design of an aqueous electrolyte and the development of sustainable and safe high-performance batteries.

关键词： Lithium-ion battery(LIB) Aqueous electrolyte Gel electrolyte Electrochemical stability window Li dendrite

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Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

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Protein & Cell 2024年第5期15卷 315-330页

作者： Alkmini T.Anastasiadi Vasiliki-Zoi Arvaniti Krystalyn E.Hudson Anastasios G.Kriebardis Constantinos Stathopoulos Angelo D’Alessandro Steven L.Spitalnik Vassilis L.Tzounakas department of Biochemistry School of MedicineUniversity of Patras26504 PatrasGreece department of Pathology and Cell Biology Columbia University Irving Medical CenterNew York CityNY 10032USA Laboratory of Reliability and Quality Control in Laboratory Hematology(HemQcR) Department of Biomedical SciencesSchool of Health&Caring SciencesUniversity of West Attica(UniWA)12243 EgaleoGreece department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus13001 AuroraCOUSA present address:Institute for Fundamental Biomedical Research(IFBR) Biomedical Sciences Research Center“Alexander Fleming”Vari11527 AthensGreece

We need to talk about red blood cells.Eukaryotic cells are defined as cells containing distinct nuclei and other membranous organelles.However,red blood cells(RBCs)lack a nucleus and organelles—perhaps to limit the generation of reactive oxygen species(Zhang et al.,2011)—and are filled with hemoglobin(Hb).This oxygen carrier is limited to the cytosol by the cell membrane and cytoskeleton,which maintain cellular integrity and deformability as RBCs pass through narrow capillaries(Gratzer,1994)to perform their primary function of gas exchange.

关键词： al. membranous maintain

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Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

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Nano-Micro Letters 2024年第4期16卷 269-292页

作者： Moon Sung Kang Yeuni Yu Rowoon Park Hye Jin Heo Seok Hyun Lee Suck Won Hong Yun Hak Kim Dong‑Wook Han department of Cogno‑Mechatronics Engineering College of Nanoscience and NanotechnologyPusan National UniversityBusan 46241Republic of Korea Medical Research Institute School of MedicinePusan National UniversityYangsan 50612Republic of Korea department of Anatomy School of MedicinePusan National UniversityYangsan 50612Republic of Korea Engineering Research Center for Color‑Modulated Extra‑Sensory Perception Technology Pusan National UniversityBusan 46241Republic of Korea department of Biomedical Informatics School of MedicinePusan National UniversityYangsan 50612Republic of Korea Periodontal Disease Signaling Network Research Center and Dental and Life Science Institute School of DentistryPusan National UniversityYangsan 50612Republic of Korea BIO‑IT Fusion Technology Research Institute Pusan National UniversityBusan 46241Republic of Korea present address:Osstem Implant Inc. Seoul 07789Republic of Korea

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

关键词： Ti_(3)C_(2)T_(x)MXene nanoparticle Ternary nanofibrous matrices Myogenesis Regeneration of volumetric muscle loss Next generation sequencing

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Hepatocellular carcinoma presenting as an extrahepatic mass:A case report and review of literature

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2241-2252页

作者： Wei Kelly Wu Krutika Patel Chandrasekhar Padmanabhan Kamran Idrees department of Surgery Vanderbilt University Medical CenterNashvilleTN 37232United States department of Pathology Microbiology and ImmunologyVanderbilt University Medical CenterNashvilleTN 37232United States Division of Surgical Oncology and Endocrine Surgery Department of SurgeryVanderbilt University Medical CenterNashvilleTN 37232United States

BACKGROUND Hepatocellular carcinoma(HCC)is a primary liver tumor generally diagnosed based on radiographic findings.Metastatic disease is typically associated with increased tumor diameter,multifocality,and vascular invasion.We report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography(CT).We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic HCC.CASE SUMMARY A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval,mixed cystic-solid mass.Serial CT evaluations demonstrated steatosis,but no cirrhosis or liver lesions.Endoscopic ultrasound demonstrated a normal-appearing pancreas,biliary tree,and liver.Fine needle aspiration yielded atypical cells.The differential diagnosis included duodenal or pancreatic cyst,lymphoproliferative cyst,stromal or mesenchymal lesions,nodal involvement from gastrointestinal or hematologic malignancy,or duodenal gastrointestinal stromal tumor.After review by a multidisciplinary tumor board,the patient underwent open surgical resection of a 5.2 cm×5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated HCC.Magnetic resonance imaging(MRI)subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement,fatty sparing,and intrinsic T1 hyperintensity.Alpha fetoprotein was 23.3 ng/mL.The patient was diagnosed with HCC with portocaval nodal involvement.Review:We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic HCC.We identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions,and 30 cases of extrahepatic HCC found to be primary,ectopic HCC.CONCLUSION Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of occult primary.In patients with risk factors fo

关键词： Extrahepatic Metastasis Portocaval Lymph node Case report

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Gas microchannel plate-pixel detector for X-ray polarimetry

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Nuclear Science and Techniques 2024年第5期35卷 60-73页

作者： Huan-Bo Feng Hong-Bang Liu Dong Wang Zi-Li Li Shu-Lin Liu Qian Liu Hang-Zhou Li Bin-Long Wang Yan-Jun Xie Zong-Wang Fan Hui Wang Ran Chen Di-Fan Yi Rui-Ting Ma Fei Xie Bo Peng Xiang-Ming Sun Jin Li En-Wei Liang present address:Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and TechnologyGuangxi UniversityNanning 530004China PLAC Key Laboratory of Quark and Lepton Physics(MOE)Central China Normal UniversityWuhan 430079China School of Science Huzhou UniversityHuzhou 313000China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China School of Physical Science University of Chinese Academy of SciencesBeijing 100049China The 13th Research Institute of China Electronics Technology Group Corporation Shijiazhuang 050057China

POLAR-2 is a gamma-ray burst(GRB)polarimeter that is designed to study the polarization in GRB radiation emissions,aiming to improve our knowledge of related mechanisms.POLAR-2 is expected to utilize an on-board polarimeter that is sensitive to soft X-rays(2-10 keV),called low-energy polarization detector.We have developed a new soft X-ray polari-zation detector prototype based on gas microchannel plates(GMCPs)and pixel chips(Topmetal).The GMCPs have bulk resistance,which prevents charging-up effects and ensures gain stability during operation.The detector is composed of low outgassing materials and is gas-sealed using a laser welding technique,ensuring long-term stability.A modulation factor of 41.28%±0.64% is obtained for a 4.5 keV polarized X-ray beam.A residual modulation of 1.96%±0.58% at 5.9 keV is observed for the entire sensitive area.

关键词： X-ray polarimetry Gas microchannel plate-pixel detector Gamma-ray bursts

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Fecal calprotectin in pediatric gastrointestinal diseases:Pros and cons

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World Journal of Clinical Pediatrics 2024年第2期13卷 198-220页

作者： Mohammed Al-Beltagi Nermin Kamal Saeed Adel Salah Bediwy Reem Elbeltagi department of Pediatric Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt department of Pediatrics University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671ManamaBahrain department of Pediatrics University Medical CenterDr.Sulaiman Al Habib Medical GroupBahrainManama 26671ManamaBahrain Medical microbiology Section Department of PathologySalmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 12ManamaBahrain Medical microbiology Section Department of PathologyIrish Royal College of SurgeonBahrainBusaiteen 15503MuharraqBahrain department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527AlghrabiaEgypt department of Pulmonology University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671ManamaBahrain department of Pulmonology University Medical CenterKing Abdulla Medical CityDr.Sulaiman Al Habib Medical GroupManama 26671ManamaBahrain department of Medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503MuharraqBahrain

BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

关键词： Fecal calprotectin Pediatric gastrointestinal diseases Functional gastrointestinal disorders Inflammatory bowel disease Coeliac disease COVID-19-induced gastrointestinal disorders Infectious gastroenteritis Cystic fibrosis

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Adeno-associated virus as a delivery vector for gene therapy of human diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1808-1840页

作者： Jiang-Hui Wang Dominic J.Gessler Wei Zhan Thomas L.Gallagher Guangping Gao Horae Gene Therapy Center University of Massachusetts Chan Medical SchoolWorcesterMA01605USA department of microbiology and Physiological Systems University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Centre for Eye Research Australia Royal Victorian Eye and Ear HospitalEast MelbourneVIC3002Australia Ophthalmology Department of SurgeryUniversity of MelbourneEast MelbourneVIC3002Australia department of Neurological Surgery University of Massachusetts Chan Medical SchoolWorcesterMA01605USA department of Neurosurgery University of MinnesotaMinneapolisMN55455USA department of Medicine University of Massachusetts Chan Medical SchoolWorcesterMA01605USA Li Weibo Institute for Rare Diseases Research University of Massachusetts Chan Medical SchoolWorcesterMA01605USA

Adeno-associated virus(AAV)has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues.Recombinant AAV(rAAV)has been engineered for enhanced specificity and developed as a tool for treating various diseases.However,as rAAV is being more widely used as a therapy,the increased demand has created challenges for the existing manufacturing methods.Seven rAAV-based gene therapy products have received regulatory approval,but there continue to be concerns about safely using high-dose viral therapies in humans,including immune responses and adverse effects such as genotoxicity,hepatotoxicity,thrombotic microangiopathy,and neurotoxicity.In this review,we explore AAV biology with an emphasis on current vector engineering strategies and manufacturing technologies.We discuss how rAAVs are being employed in ongoing clinical trials for ocular,neurological,metabolic,hematological,neuromuscular,and cardiovascular diseases as well as cancers.We outline immune responses triggered by rAAV,address associated side effects,and discuss strategies to mitigate these reactions.We hope that discussing recent advancements and current challenges in the field will be a helpful guide for researchers and clinicians navigating the ever-evolving landscape of rAAV-based gene therapy.

关键词： diseases specificity approval

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