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Contribution of Metabolic Imaging in the Exploration of Cognitive Disorders Related to COVID-19

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Advances in Molecular Imaging 2024年第1期13卷 1-5页

作者： Serigne Moussa Badiane Amadou Barro Elhadji Amadou Lamine Bathily Louis Augustin Diaga Diouf biophysics and nuclear medicine Gaston Berger University Saint-Louis Senegal ENT Department Fann University Hospital Dakar Senegal biophysics and nuclear medicine Cheikh Anta Diop University Dakar Senegal

On March 11, 2019, the WHO declared COVID-19 a pandemic disease. It is a respiratory tropism SARS COV 2 infection. In the emergency of the pandemic, in medical imaging, only computed tomography (CT) of the lungs was favored to assess lung lesions. In addition, many cases of post-COVID-19 cognitive disorders have been reported. As the curve dips and services restart correctly, other imaging techniques have been used to better explore the disease. The objective of this presentation is to illustrate the contribution of metabolic imaging in the exploration of post COVID-19 cognitive disorders and to discuss the pathophysiological mechanisms. Hypometabolism brain lesions are objective signs of functional impairment whose pathophysiological mechanism is not yet fully understood. Metabolic imaging with PET-SCAN is a suitable tool for exploring these disorders, both for the severity and extent of the lesions and for the topography of the brain damage.

关键词： COVID-19 nuclear medicine Cognitive Disorders PET-SCAN

Crocus genome reveals the evolutionary origin of crocin biosynthesis

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1878-1891页

作者： Zhichao Xu Shanshan Chen Yalin Wang Ya Tian Xiaotong Wang Tianyi Xin Zishan Li Xin Hua Shengnan Tan Wei Sun Xiangdong Pu Hui Yao Ranran Gao Jingyuan Song Key Lab of Chinese medicine Resources Conservation State Administration of Traditional Chinese Medicine of the People's Republic of ChinaInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China State Key laboratory of Basis and New Drug Development of Natural and nuclear Drugs Engineering Research Center of Chinese Medicine ResourceMinistry of EducationBeijing 100193China College of Life Science Northeast Forestry UniversityHarbin 150040China Key laboratory of Beijing for Identification and Safety Evaluation of Chinese medicine China Academy of Chinese Medical SciencesInstitute of Chinese Materia MedicaBeijing 100700China Analysis and Testing Center of Northeast Forestry University Harbin 150040China School of Pharmacy Anhui Medical UniversityInflammation and Immune Mediated Diseases Laboratory of Anhui ProvinceHefei 230032China

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

关键词： Crocus sativus WGT Crocin biosynthesis Carotenoids Apocarotenoids CCDs

A novel method to assess antibody-dependent cell-mediated cytotoxicity against influenza A virus M2 in immunized murine models

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Biosafety and Health 2024年第3期6卷 178-185页

作者： Yinjie Liang Junjia Guo Zhen Li Shiyuan Liu Ting Zhang Shucai Sun Funa Lu Yuqian Zhai Wenling Wang Chuanyi Ning Wenjie Tan Collaborative Innovation Centre of Regenerative medicine and medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China Key laboratory of Biosafety National Health Commission of the People’s Republic of ChinaNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China School of laboratory medicine Wenzhou Medical UniversityWenzhou 325035China School of Public Health Baotou Medical CollegeBaotou 014040China Department of nuclear medicine The Second Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Microbiology School of Basic MedicineInner Mongolia Medical UniversityHohhot 010110China

The matrix protein 2 (M2) is a preferred target for developing a universal vaccine against the influenza A virus (IAV). This study aimed to develop a method for assessing antibody-dependent cell-mediated cytotoxicity (ADCC) associated with M2-based immunization in mice. We first established a stable cell line derived from mouse lymphoma cells (YAC-1) expressing M2 of H3N2. This cell line, designated as YAC-1-M2, was generated using a second-generation lentiviral tricistronic plasmid system to transduce the M2 gene into YAC-1 cells. The ADCC effect induced by polyclonal antibodies targeting matrix protein 2 ectodomain (M2e) was demonstrated by YAC-1-M2 cell lysis by natural killer cells (NK) derived from mice, in the presence of anti-M2 antibodies obtained from mice immunized with an mRNA vaccine based on M2e. This ADCC effect was found to be stronger compared to the effect induced by monoclonal antibodies (14C2) against M2. Moreover, the ADCC effect was enhanced as the effector-to-target ratio of NK to YAC-1-M2 cells increased. In conclusion, we established a novel method to detect ADCC of M2 of IAV, which paves the way for the development of an M2-based universal vaccine against IAV and an in-depth analysis of its mechanism of broad-spectrum immune protection in mice.

关键词： Antibody-dependent cell-mediated cytotoxicity(ADCC) Influenza A virus(IAV) Matrix protein 2 extracellular domain(M2e) Cell line

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Asymptomatic recurrence in patients with pulmonary embolism

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Chinese medical Journal 2024年第9期137卷 1118-1120页

作者： Song Hu Lei Wang Jiangshan Tan Wei Fang Xinghong Ma Tingting Guo Xin Gao Yan Wu Yuzi Zhou Li Wang Lu Hua State Key laboratory of Cardiovascular Disease National Center for Cardiovascular DiseasesFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of nuclear medicine National Center for Cardiovascular DiseasesFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Key laboratory of Pulmonary Vascular medicine Department of CardiologyNational Clinical Research Center of Cardiovascular DiseasesNational Center for Cardiovascular DiseasesFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Fuwai Shenzhen Hospital Chinese Academy of Medical SciencesShenzhenGuangdong 518057China

To the Editor:Pulmonary embolism(PE)is the third most common cause of cardiovascular-related death worldwide after stroke and heart *** a consequence of hemodynamic differences,patients with PE present a wide spectrum of clinical manifestations,ranging from asymptomatic to life-threatening *** are high rates of recurrence in PE patients,and although most patients survive after the initial phase of the disease,the risk of recurrence remains throughout *** to patients experiencing theirrst PE episodes,patients with recurrent PE may be *** date,much of our knowledge about recurrent PE has come from clinical trials or registry studies in which symptomatic recurrence was a major endpoint,while asymptomatic recurrence is rarely ***,current guidelines suggest treating patients with asymptomatic PE similarly to those with symptomatic PE,[1,2]but do not recommend routine follow-up of asymptomatic patients by imaging methods after PE diagnosis.

关键词： patients routine clinical

Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2467-2479页

作者： Yong Tang Jing Wei Xiao-Fang Wang Tao Long Xiaohong Xiang Liqun Qu Xingxia Wang Chonglin Yu Xingli Xiao Xueyuan Hu Jing Zeng Qin Xu Anguo Wu Jianming Wu Dalian Qin Xiaogang Zhou Betty Yuen-Kwan Law Dr.Neher’s biophysics laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administrative RegionChina Sichuan Key medical laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica Southwest Medical UniversityLuzhouSichuan ProvinceChina Eye School and Key laboratory of Sichuan Province Ophthalmopathy Prevention&Cure and Visual Function Protection of Chengdu University of TCM ChengduSichuan ProvinceChina School of Basic medical Sciences Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Neurology The First People’s Hospital of NeijiangNeijiangSichuan ProvinceChina

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s *** Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains *** the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first *** Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of *** addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo ***,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was *** importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease *** revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

关键词： Alzheimer’s disease amyloid-beta apoptosis autophagy Caenorhabditis elegans Citri Reticulatae Semen

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 25-35页

作者： Zhuanzhuan Mu Xin Zhang Dongquan Liang Jugao Fang Ge Chen Wenting Guo Di Sun Yuqing Sun Zhentian Kai Lisha Huang Jun Liang Yansong Lin Department of nuclear medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Beijing Key laboratory of Molecular Targeted Diagnosis and Therapy in nuclear medicine Beijing 100730China Pepperdine University Graduate School of Education and Psychology Los Angeles 90045USA Department of Head and Neck Surgery Affiliated Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Central laboratory State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Department of Bioinformatics Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of medicine Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Oncology Peking University International HospitalBeijing 102206China

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively ***: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low ***: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

关键词： Differentiated thyroid cancer distant metastases genetic alterations RAI refractoriness molecular risk stratification

A biocompatible Horner-Wadsworth-Emmons(HWE)reaction triggered by a bioorthogonal proximity-induced platform

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Chinese Chemical Letters 2024年第8期35卷 217-220页

作者： Yayue Wang Haojie Yang Jie Li Qiao Kong Siming Zhou Hongbao Sun Lili Pan Qiyong Gong Ping Feng Haoxing Wu Department of Radiology and Huaxi MR Research Center(HMRRC) Functional and Molecular Imaging Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan UniversityChengdu 610041China Department of nuclear medicine Laboratory of Clinical Nuclear MedicineWest China HospitalSichuan UniversityChengdu 610041China Reseacrch Unit of Psychoradiology Chinese Academy of Medical SciencesChengdu 610041China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610041China Clinical Trial Center and National medical Products Administration Key laboratory for Clinical Research and Evaluation of Innovative Drugs West China HospitalSichuan UniversityChengdu 610041China

Here,we present a novel bioorthogonal platform that enables precise positioning of attached moieties in close proximity,thereby facilitating the discovery and optimization of biocompatible *** this platform,we achieve a Horner-Wadsworth-Emmons(HWE)reaction under physiological conditions,generating a fluorophore in situ with a yield of up to 93%.This proximity platform should facilitate the discovery of various types of biocompatible reactions,making it a versatile tool for biomedical applica-tions.

关键词： Biocompatible reactions Horner-Wadsworth-Emmons reaction Bioorthogonal reactions Tetrazines Proximity effects

Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1665-1674页

作者： Jie Xiong Shu Cheng Xiao Gao Shan-He Yu Yu-Ting Dai Xin-Yun Huang Hui-Juan Zhong Chao-Fu Wang Hong-Mei Yi Hao Zhang Wei-Guo Cao Rong Li Wei Tang Yan Zhao Peng-Peng Xu Li Wang Wei-Li Zhao 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 MedicineShanghaiChina Department of nuclear medicine Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Otolaryngology Shanghai Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Radiation Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Hematology Navy Medical Center of PLAShanghaiChina Pole de Recherches Sino-Francais en Science du Vivant et Genomique Laboratory of Molecular PathologyShanghaiChina

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive *** explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 *** complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),*** a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),*** most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of *** proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab *** conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage *** lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关键词： killer metabolism lymphoma

VX-509 attenuates the stemness characteristics of colorectal cancer stem-like cells by regulating the epithelial-mesenchymal transition through Nodal/Smad2/3 signaling

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World Journal of Stem Cells 2024年第2期16卷 207-227页

作者： Yun Yuan Xu-Fan Zhang Yu-Chen Li Hong-Qing Chen Tian Wen Jia-Lian Zheng Zi-Yi Zhao Qiong-Ying Hu Department of laboratory medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina Department of nuclear medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina College of medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina Department of Hepatology Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110032Liaoning ProvinceChina Hospital of Chengdu University of Traditional Chinese medicine Chengdu 610072Sichuan ProvinceChina Traditional Chinese medicine Regulating Metabolic Diseases Key laboratory of Sichuan Province Chengdu 610072Sichuan ProvinceChina

BACKGROUND Colorectal cancer stem cells(CCSCs)are heterogeneous cells that can self-renew and undergo multidirectional differentiation in colorectal cancer(CRC)*** are generally accepted to be important sources of CRC and are responsible for the progression,metastasis,and therapeutic resistance of ***,targeting this specific subpopulation has been recognized as a promising strategy for overcoming *** To investigate the effect of VX-509 on CCSCs and elucidate the underlying *** CCSCs were enriched from CRC cell lines by in conditioned serum-free *** blot,Aldefluor,transwell and tumorigenesis assays were performed to verify the phenotypic characteristics of the *** anticancer efficacy of VX-509 was assessed in HCT116 CCSCs and HT29 CCSCs by performing cell viability analysis,colony formation,sphere formation,flow cytometry,and western blotting assessments in vitro and tumor growth,immunohistochemistry and immunofluorescence assessments in *** Compared with parental cells,sphere cells derived from HCT116 and HT29 cells presented increased expression of stem cell transcription factors and stem cell markers and were more potent at promoting migration and tumori-genesis,demonstrating that the CRC sphere cells displayed CSC ***-509 inhibited the tumor malignant biological behavior of CRC-stem-like cells,as indicated by their proliferation,migration and clonality in vitro,and suppressed the tumor of CCSC-derived xenograft tumors in ***,VX-509 suppressed the CSC character-istics of CRC-stem-like cells and inhibited the progression of epithelial-mesenchymal transition(EMT)signaling in *** was identified as the regulatory factor of VX-509 on CRC stem-like cells through analyses of differen-tially expressed genes and CSC-related database ***-509 markedly downregulated the expression of Nodal and its downstream phosphorylated Smad2/3 to inhibit EMT ***,VX-509 rev

关键词： Colorectal cancer stem cells Stemness VX-509 Epithelial-mesenchymal transition Nodal