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Development and Characterization of Novel FAP-Targeted Theranostic Pairs: A Bench-to-Bedside Study

Research 2024年第3期2023卷 473-485页

作者： Wei Huang Yizhen Pang Qiufang Liu Chenyi Liang Shuxian An Qianyun Wu You Zhang Gang Huang Haojun Chen Jianjun Liu Weijun Wei department of Nuclear medicine Institute of Clinical Nuclear MedicineRenj HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghai 200127China department of Nuclear medicine and Minnan PET Center Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361003China department of Nuclear medicine Fudan University Shanghai Cancer CenterFudan UniversityShanghai 200032China

Fibroblast activation protein (FAP) is among the most popular targets in nuclear medicine imaging and cancer theranostics. Several small-molecule moieties (FAPI-04, FAPI-46, etc.) are used for developing FAP-targeted theranostic agents. Nonetheless, the circulation time of FAP inhibitors is relatively short, resulting in rapid clearance via kidneys, low tumor uptake, and associated unsatisfactory treatment efficacy. To address the existing drawbacks, we engineered 3 peptides named FD1, FD2, and FD3 with different circulation times through solid-phase peptide synthesis. All the 3 reported peptides bind to human and murine FAP with single-digit nanomolar affinity measured by surface plasmon resonance. The diagnostic and therapeutic potential of the agents labeled with 68Ga and 177Lu was assessed in several tumor models exhibiting different levels of FAP expression. While radiolabeled FD1 was rapidly excreted from kidneys, radiolabeled FD2/FD3 have significantly prolonged circulation, increased tumor uptake, and decreased kidney accumulation. Our findings indicated that [68Ga]Ga-DOTA-FD1 positron emission tomography (PET) effectively detected FAP dynamics, whereas [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 exhibited remarkable therapeutic efficacy in FAP-overexpressing tumor models, including pancreatic cancer cell models characterized by abundant stroma. Moreover, a pilot translational investigation demonstrated that [68Ga]Ga-DOTA-FD1 had the capability to identify both primary and metastatic tumors with precision and distinction. In summary, we developed [68Ga]Ga-DOTA-FD1 for same-day PET imaging of FAP dynamics and [177Lu]Lu-DOTA-FD2 and [177Lu]Lu-DOTA-FD3 for effective radioligand therapy of FAP-overexpressing tumors.

关键词： DOTA expressing labeled

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Utilization of biomarkers for the prognostic prediction of cardiac arrest survivors using a multi-modal approach

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World Journal of Emergency medicine 2024年第2期15卷 131-134页

作者： Changshin Kang Yeonho You Jung Soo Park Byeong Kwon Park Jae Kwang Lee Byung Kook Lee department of Emergency medicine College of MedicineChungnam National UniversityDaejeon 35015Republic of Korea department of Emergency medicine Chungnam National University HospitalDaejoen 35015Republic of Korea department of Emergency medicine Konyang University HospitalCollege of MedicineDaejeon 35015Republic of Korea department of Emergency medicine Chonnam National University Medical SchoolChonnam National University HospitalGwangju 61469Republic of Korea

International guidelines for post-cardiac arrest care recommend using multi-modal strategies to avoid the withdrawal of life-sustaining therapy(WLST)in patients with the potential for neurological recovery.[1]However,a clear methodology for multi-modal approaches has yet to be ***-specific enolase(NSE)is currently the only recommended biomarker,and the European Resuscitation Council(ERC)and the European SocietyofIntensiveCaremedicine(ESICM)have proposed a cutoff value of 60μg/L at 48 and/or 72 h after the return of spontaneous circulation(ROSC)as a multimodal prognostic tool for predicting poor neurological outcomes.

关键词： cardiac modal return

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Autophagy in neural stem cells and glia for brain health and diseases

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Neural Regeneration Research 2024年第4期19卷 729-736页

作者： Aarti Nagayach Chenran Wang department of Cancer Biology University of Cincinnati College of Medicine

Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and *** facilities the utilization of energy and the microenvironment for developing neural stem *** arbitrates structural and functional remodeling during the cell differentiation *** also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of *** recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the *** cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured ***,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative *** review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.

关键词： astrocyte autophagy glia microglia neural stem cells neurodegenerative diseases neurodevelopmental disorders oligodendrocyte

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Bilateral adrenal histoplasmosis in a Malaysian tertiary hospital:Report of four cases

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Asian Pacific Journal of Tropical medicine 2024年第2期17卷 91-94页

作者： Kang WH Norasyikin Abdul Wahab department of medicine Faculty of Medicine and Health SciencesUniversity Tunku Abdul RahmanMalaysia department of medicine Pusat Perubatan Universiti KebangsaanMalaysia

Rationale:Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal *** these patients are initially investigated as secondary adrenal metastases before eventually their diagnosis established by histopathological examination of the adrenal *** concerns:We report 4 cases of patients aged 55-78 who presented with hypocortisolism and bilateral adrenal ***:Bilateral adrenal ***:Three patients received antifungal treatment for at least one year while 1 patient passed away before the initiation of antifungal ***:Two patients’adrenal function recovered not requiring any steroid replacement,while 1 patient still requires long-term steroid ***:Adrenal histoplasmosis should be excluded in patients from endemic areas presenting with bilateral adrenal masses and adrenal *** patients have an exposure to bird droppings,bat guano or soil contaminated with histoplasmosis *** examination of biopsied adrenal tissues is still the gold standard investigation as serology and molecular diagnostic methods are still not widely available in most centers in Malaysia.

关键词： Adrenal histoplasmosis Histoplasmosis Bilateral adrenal masses

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Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units

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Neural Regeneration Research 2024年第4期19卷 887-894页

作者： Yifang Wu Jun Sun Qi Lin Dapeng Wang Jian Hai department of Neurosurgery Tongji HospitalSchool of MedicineTongji University department of Pharmacy Institute of Medical SciencesShanghai Jiao Tong University School of Medicine

Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor(VEGFA/b FGF)expression in the penumbra of cerebral ischemia can increase vascular volume,reduce lesion volume,and enhance neural cell proliferation and differentiation,thereby exerting neuroprotective ***,the beneficial effects of endogenous VEGFA/b FGF are limited as their expression is only transiently *** this study,we generated multilayered nanofiber membranes loaded with VEGFA/b FGF using layer-by-layer self-assembly and electrospinning *** found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 *** 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation,inhibited neuronal apoptosis,upregulated the expression of tight junction proteins,and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose ***,this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3(JAK2/STAT3),Bax/Bcl-2,and cleaved ***,this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

关键词： brain ischemia brain microvascular endothelial cell nanofiber membrane neurovascular unit

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Commentary on“Desialylated Platelets Maintain Immune Quiescence through Regulating Kupffer Cells”

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Research 2024年第3期6卷 621-623页

作者： Chen Li Craig N.Morrell Aab Cardiovascular Research Institute University of Rochester School of Medicine and DentistryRochesterNYUSA department of Pharmacology and Physiology University of Rochester School of Medicine and DentistryRochesterNYUSA department of medicine University of Rochester School of Medicine and DentistryRochesterNYUSA department of Microbiology and Immunology University of Rochester School of Medicine and DentistryRochesterNYUSA department of Pathology and Laboratory medicine University of Rochester School of Medicine and DentistryRochesterNYUSA.

Platelets have long been studied for their roles in hemostasis and vascular injury repair. However, there is a continually evolving and deepening understanding that platelets initiate and regulate responses to tissue injury and pathogens, leading to platelets now being considered immune modulatory cells [1]. Platelets actively participate in host immune responses directly through pathogen engulfing and killing, or by regulating both innate and adaptive immune responses to infection or tissue injury [2]. Activated platelets promote inflammatory responses to tissue injury or infection by direct contact dependent interactions with immune cells and through indirect interactions via released soluble factors. However, mice that are deficient in platelets have skewed T helper cell differentiation [3] and increased vascular permeability [4], implying poorly defined roles for platelets in maintaining healthy immune homeostasis.

关键词： Platelet homeostasis Immune

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tRNA^(Glu)-derived fragments from embryonic extracellular vesicles modulate bovine embryo hatching

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1559-1566页

作者： Yuan Fan Krishna Chaitanya Pavani Katrien Smits Ann Van Soom Luc Peelman department of Veterinary and Biosciences Faculty of Veterinary MedicineGhent UniversityHeidestraat 199820 MerelbekeBelgium department of Internal medicine Reproduction and Population MedicineFaculty of Veterinary MedicineGhent UniversitySalisburylaan 1339820 MerelbekeBelgium department for Reproductive medicine Ghent University HospitalCorneel Heymanslaan 109000 GhentBelgium

Transfer RNA-derived small RNAs(tsRNAs)have been shown to be involved in early embryo development and repression of endogenous retroelements in embryos and stem ***,it is unknown whether tsRNAs also regulate embryo *** this study,we mined the sequencing data of a previous experiment in which we demonstrated that the microRNA(miRNA)cargo of preimplantation embryonic extracellular vesicles(EVs)influences embryo *** thus profiled the tsRNA cargo of EVs secreted by blastocysts and *** majority of tsRNAs was identified as tRNA halves originating from the 5'ends of *** the 148 differentially expressed tsRNAs,the 19 nt tRNA fragment(tRF)tDR-14:32-Glu-CTC-1 was found to be significantly up-regulated in EVs derived from ***-qPCR assays confirmed its significant up-regulation in non-blastocyst embryos and their conditioned medium compared to the blastocyst group(P<0.05).Inhibition of tDR-14:32-Glu-CTC-1 by supplementing antagomirs to the conditioned medium improved embryo hatching(P<0.05).Transcriptomic analysis of embryos treated with tDR-14:32-Glu-CTC-1 antagomirs further showed differential expression of genes that are associated with embryo hatching and *** summary,tDR-14:32-Glu-CTC-1 is up-regulated in non-blastocyst embryos and their secretions,and inhibition of tDR-14:32-Glu-CTC-1 promotes embryo hatching,while influencing embryo implantation-related genes and *** results indicate that embryonic EVs containing specific tRFs may regulate preimplantation embryo development.

关键词： Embryo Extracellular vesicles Hatching tRNA fragments ts RNAs

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Vaccination for solid organ transplanted patients:Recommendations,efficacy,and safety

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World Journal of Transplantation 2024年第4期14卷 6-14页

作者： Tsvetelina Velikova Stavros Gerasoudis Hristiana Batselova Medical Faculty Sofia University St.Kliment OhridskiSofia 1407Bulgaria Faculty of medicine Trakia UniversityStara Zagora 6000Bulgaria department of epidemiology and Disaster medicine Medical UniversityUniversity Hospital“St George”Plovdiv 4000Bulgaria

Solid organ transplant recipients face unique challenges in managing their im-munosuppressed status,making vaccination a critical *** review aimed to comprehensively analyze current recommendations,evaluate the effi-cacy of vaccinations in this population,and assess safety *** explored the latest evidence on vaccine types,timing,and potential benefits for transplant patients,highlighting the importance of individualized approaches for routinely used vaccines as well as coronavirus disease 2019 *** synthesizing avai-lable data,this review underscored the pressing need to optimize vaccination strategies,ensuring that transplant recipients can obtain the full protection against many pathogens while minimizing risks associated with their post-transplant immunosuppression.

关键词： Vaccination Solid organ transplant Immunosuppression Transplant reci-pients Vaccine efficacy Safety COVID-19 vaccines Immunization strategies Post-transplant immunity Clinical recommendations

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Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

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Biomedical and Environmental Sciences 2024年第7期37卷 762-773页

作者： Yamei Li Xiang Xiao Jie Wang Yixu Liu Xiongfeng Pan Haibin Yu Jiayou Luo Miyang Luo department of epidemiology and Health Statistics School of Public HealthUniversity of South ChinaHengyang 421001HunanChina department of Maternal and Child Health Xiangya School of Public HealthCentral South UniversityChangsha 410008HunanChina Supervision and Inspection department of Shanghai Healthcare Security Bureau Shanghai 200003China department of epidemiology and Health Statistics Xiangya School of Public HealthCentral South UniversityChangsha 410008HunanChina

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically ***-analyses of the genetic variants were conducted using at least five data *** epidemiologic credibility of the significant associations was graded using the Venice *** Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing *** identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the *** meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

关键词： Nonalcoholic fatty liver disease Genetic association study Genetic variant Systematic review Meta-analysis

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Metallothionein 1E Alleviates Cadmium-induced Renal Cytotoxicity through Promoting Mitochondrial Functional Recovery

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Biomedical and Environmental Sciences 2024年第1期37卷 117-121页

作者： WEN Si Hui LI Lu Bei HUANG Hui Dan XIE Ying LUO Lei Key Laboratory of Molecular epidemiology of Hunan Province School of MedicineHunan Normal UniversityChangsha 410081HunanChina department of Occupational Health Changsha Centre for Disease Control and PreventionChangsha 410004HunanChina The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province Hunan Normal University School of MedicineChangsha 410013HunanChina

The pervasive utilization of industrial substances has escalated human exposure to cadmium(Cd),a metal associated with long-term negative health outcomes such as renal dysfunction,neurological disorders,and various cancers^([1]).Once ingested by humans,Cd interacts with cysteine-rich metallothioneins(MTs)which have metal-binding and antioxidant properties and is subsequently transported to the kidney^([2]).

关键词： Renal kidney cadmium

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