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Chinese Chemical Letters 2024年第7期35卷 264-270页

作者： Yan-Bo Li Yi Li Liang Yin CAS Key Laboratory of Synthetic Chemistry of Natural Substances Centre for Excellence in Molecular SynthesisShanghai Institute of Organic ChemistryUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200032China

A copper(Ⅰ)-catalyzed diastereodivergent addition of phosphinothioates(HP(S)ROR')toα,β-unsaturated thioamides is disclosed,which constructs vicinal P-chiral and C-chiral centers in generally high diastereoand *** this reaction,the kinetic resolution of HP(S)ROR'occurs,which affords(R)-HP(S)Ph OMe in high enantioselectivity in the addition with(R,R)-Ph-BPE as the *** is found through control experiment that dual“soft-soft”interaction,indicated by both1H and31P NMR experiments,is indispensable in the present *** first“soft-soft”interaction between copper(Ⅰ)catalyst and HP(S)ROR'enables facile deprotonation to generate nucleophilic[Cu]-SPROR'*** second one between the[Cu]-SPROR'species andα,β-unsaturated thioamides facilitated the nucleophilic ***,both Michael adducts and(R)-HP(S)PhOMe are easily converted to synthetically useful compounds.

关键词： Copper catalysis Asymmetric catalysis Diastereodivergent synthesis P-Chirality "Soft-soft"interaction

Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel Brian Zanotti Michael V.Volin M.Asif Amin Myles J.Lewis Costantino Pitzalis Shiva Arami Joseph A.Karam Nadera J.Sweiss Shiva Shahrara Jesse Brown VA Medical Center ChicagoILUSA Department of medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA centre for Experimental medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom centre for Experimental medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

Present situation of minimally invasive surgical treatment for early gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1154-1165页

作者： Chun-Yan Li Yi-Feng Wang Li-Kang Luo Xiao-Jun Yang The First Clinical Medical School Lanzhou UniversityLanzhou 730000Gansu ProvinceChina The First Clinical medicine College Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina General Surgery Clinical centre Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina The Second Department of General Surgery Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Lanzhou University People's Clinical Hospital Lanzhou 730000Gansu ProvinceChina Gansu Research Center of Prevention and Control Project for Digestive Oncology Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Gansu Key Laboratory of molecular Diagnostics and Precision medicine for Surgical Oncology Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

Minimally invasive surgery is a kind of surgical operation,which is performed by using professional surgical instruments and equipment to inactivate,resect,repair or reconstruct the pathological changes,deformities and wounds in human body through micro-trauma or micro-approach,in order to achieve the goal of treatment,its surgical effect is equivalent to the traditional open surgery,while avoiding the morbidity of conventional surgical *** addition,it also has the advantages of less trauma,less blood loss during operation,less psychological burden and quick recovery on patients,and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer *** minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer(EGC):endoscopic mucosal resection(EMR),underwater EMR(UEMR),endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR),endoscopic submu-cosal excavation(ESE),submucosal tunnel endoscopic resection,laparoscopic and endoscopic cooperative surgery(LECS);Among them,EMR,EFTR and LECS technologies have a wide range of applications and different modific-ations have been derived from their respective surgical operations,such as band-assisted EMR(BA-EMR),conven-tional EMR(CEMR),over-the-scope clip-assisted EFTR,no-touch EFTR,the inverted LECS,closed LECS,and so *** new and improved minimally invasive surgeries are more precise,specific and effective in treating different types of EGC.

关键词： Minimally invasive surgery Early gastric cancer Endoscopic mucosal resection Endoscopic full-thickness resection Laparoscopic and endoscopic cooperative surgery

Simultaneously quantifying hundreds of acylcarnitines in multiple biological matrices within ten minutes using ultrahigh-performance liquid-chromatography and tandem mass spectrometry

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Journal of Pharmaceutical Analysis 2024年第1期14卷 140-148页

作者： Jingxian Zhang Qinsheng Chen Lianglong Zhang Biru Shi Men Yu Qingxia Huang Huiru Tang State Key Laboratory of Genetic Engineering School of Life SciencesHuman Phenome InstituteZhangjiang Fudan International Innovation CenterMetabonomics and Systems Biology Laboratory at Shanghai International Centre for Molecular PhenomicsZhongshan HospitalFudan UniversityShanghai200032China Wuhan Laboratory for Shanghai Metabolome Institute(SMI)Ltd. Wuhan430000China

Acylcarnitines are metabolic intermediates of fatty acids and branched-chain amino acids having vital biofunctions and pathophysiological significances. Here, we developed a high-throughput method for quantifying hundreds of acylcarnitines in one run using ultrahigh performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS). This enabled simultaneous quantification of 1136 acylcarnitines (C0–C26) within 10-min with good sensitivity (limit of detection 0.992), accuracy (relative error 0.998) for predicting retention time (tR) of acylcarnitines with no standards and built a database of their multiple reaction monitoring parameters (tR, ion-pairs, and collision energy). Furthermore, we quantified 514 acylcarnitines in human plasma and urine, mouse kidney, liver, heart, lung, and muscle. This provides a rapid method for quantifying acylcarnitines in multiple biological matrices.

关键词： Acylcarnitine UPLC-MS/MS Quantitative structure-retention relationship molecular phenotype

Development of NK cell-based cancer immunotherapies through receptor engineering

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Cellular & molecular Immunology 2024年第4期21卷 315-331页

作者： Audrey Page Nicolas Chuvin Jenny Valladeau-Guilemond Stéphane Depil centre de Recherche en Cancérologie de Lyon UMR INSERM U1052 CNRS 5286Centre Léon BérardLyonFrance ErVimmune LyonFrance centre Léon Bérard LyonFrance UniversitéClaude Bernard Lyon 1 LyonFrance

Natural killer(NK)cell-based immunotherapies are attracting increasing interest in the field of cancer *** clinical trials have shown promising outcomes,alongside satisfactory product efficacy and *** developments have greatly increased the therapeutic potential of NK cells by endowing them with enhanced recognition and cytotoxic *** review focuses on surface receptor engineering in NK cell therapy and discusses its impact,challenges,and future *** approaches are based on engineering with chimeric antigen receptors to allow NK cells to target specific tumor antigens independent of human leukocyte antigen *** approach has increased the precision and potency of NK-mediated recognition and elimination of cancer *** addition,engineering NK cells with T-cell receptors also mediates the recognition of intracellular epitopes,which broadens the range of target *** tumor peptide recognition by NK cells has also been improved by optimizing immunoglobulin constant fragment receptor expression and ***,engineered NK cells have an improved ability to recognize and destroy target cells coated with specific antibodies,thereby increasing their antibodydependent cellular *** ability of NK cell receptor engineering to promote the expansion,persistence,and infiltration of transferred cells in the tumor microenvironment has also been ***-based strategies for sustained NK cell functionality within the tumor environment have also been discussed,and these strategies providing perspectives to counteract tumor-induced ***,receptor engineering has led to significant advances in NK cell-based cancer *** technical challenges are addressed,these innovative treatments will likely reshape cancer immunotherapy.

关键词： NK cells Cell therapy Receptor engineering CAR

Impact of cancer diagnosis on life expectancy by area-level socioeconomic groups in New South Wales, Australia: a population-based study

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Cancer Biology & medicine 2024年第8期21卷 692-702页

作者： Md Mijanur Rahman Michael David David Goldsbury Karen Canfell Kou Kou Paramita Dasgupta Peter Baade Xue Qin Yu The Daffodil centre The University of SydneyA Joint Venture with Cancer Council NSWSydneyNSW 1340Australia School of medicine and Dentistry Griffith UniversityGold CoastQLD 4222Australia Cancer Council Queensland BrisbaneQLD 4006Australia

Objective: Improvement in cancer survival over recent decades has not been accompanied by a narrowing of socioeconomic disparities. This study aimed to quantify the loss of life expectancy(LOLE) resulting from a cancer diagnosis and examine disparities in LOLE based on area-level socioeconomic status(SES).Methods: Data were collected for all people between 50 and 89 years of age who were diagnosed with cancer, registered in the NSW Cancer Registry between 2001 and 2019, and underwent mortality follow-up evaluations until December 2020. Flexible parametric survival models were fitted to estimate the LOLE by gender and area-level SES for 12 common ***: Of 422,680 people with cancer, 24% and 18% lived in the most and least disadvantaged areas, respectively. Patients from the most disadvantaged areas had a significantly greater average LOLE than patients from the least disadvantaged areas for cancers with high survival rates, including prostate [2.9 years(95% CI: 2.5±3.2 years) vs. 1.6 years(95% CI: 1.3±1.9 years)] and breast cancer [1.6 years(95% CI: 1.4±1.8 years) vs. 1.2 years(95% CI: 1.0±1.4 years)]. The highest average LOLE occurred in males residing in the most disadvantaged areas with pancreatic [16.5 years(95% CI: 16.1±16.8 years) vs. 16.2 years(95% CI: 15.7±16.7 years)] and liver cancer [15.5 years(95% CI: 15.0±16.0 years) vs. 14.7 years(95% CI: 14.0±15.5 years)]. Females residing in the least disadvantaged areas with thyroid cancer [0.9 years(95% CI: 0.4±1.4 years) vs. 0.6 years(95% CI: 0.2±1.0 years)] or melanoma [0.9 years(95% CI: 0.8±1.1 years) vs. 0.7 years(95% CI: 0.5±0.8 years)] had the lowest average ***: Patients from the most disadvantaged areas had the highest LOLE with SES-based differences greatest for patients diagnosed with cancer at an early stage or cancers with higher survival rates, suggesting the need to prioritise early detection and reduce treatment-related barriers and survivorship challenges to improve life expec

关键词： Cancer diagnosis life expectancy loss of life expectancy area-level socioeconomic status flexible parametric model

Chitosan based metallic nanocomposite scaffolds as antimicrobial wound dressings

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Bioactive Materials 2018年第3期3卷 267-277页

作者： Annapoorna Mohandas S.Deepthi Raja Biswas R.Jayakumar centre for nanosciences and molecular medicine Amrita Institute of Medical Sciences and Research CenterAmrita Vishwa VidyapeethamKochi682041India

Chitosan based nanocomposite scaffolds have attracted wider applications in medicine,in the area of drug delivery,tissue engineering and wound *** matrix incorporated with nanometallic components has immense potential in the area of wound dressings due to its antimicrobial *** review focuses on the different combinations of Chitosan metal nanocomposites such as Chitosan/nAg,Chitosan/nAu,Chitosan/nCu,Chitosan/nZnO and Chitosan/nTiO2 towards enhancement of healing or infection control with special reference to the antimicrobial mechanism of action and toxicity.

关键词： Antimicrobial Chitosan nanocomposities Silver Zinc oxide Gold Copper Wound healing

Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples

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Journal of Pharmaceutical Analysis 2024年第5期14卷 733-743页

作者： Alongkorn Kurilung Suphitcha Limjiasahapong Khwanta Kaewnarin Pattipong Wisanpitayakorn Narumol Jariyasopit Kwanjeera Wanichthanarak Sitanan Sartyoungkul Stephen Choong Chee Wong Nuankanya Sathirapongsasuti Chagriya Kitiyakara Yongyut Sirivatanauksorn Sakda Khoomrung Siriraj Center of Research Excellent in Metabolomics and Systems Biology(SiCORE-MSB) Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Siriraj Metabolomics and Phenomics Center Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Department of Biomedical Informatics University of Arkansas for Medical SciencesLittle RockAR72205USA SingHealth Duke-NUS Institute of Biodiversity medicine National Cancer Centre Singapore168583Singapore Waters Pacific Pte. Ltd.Singapore117528Singapore Program in Translational medicine Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok10400Thailand Chakri Naruebodindra Medical Institute Faculty of Medicine Ramathibodi HospitalMahidol UniversitySamut Prakan10540Thailand Department of medicine Ramathibodi HospitalMahidol UniversityBangkok10400Thailand Department of Biochemistry Faculty of Medicine Siriraj HospitalMahidol UniversityBangkok10700Thailand Center of Excellence for Innovation in Chemistry(PERCH-CIC) Faculty of ScienceMahidol UniversityBangkok10400Thailand

The collision cross-sections(CCS)measurement using ion mobility spectrometry(IMS)in combination with mass spectrometry(MS)offers a great opportunity to increase confidence in metabolite ***,owing to the lack of sensitivity and resolution,IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites(VLMs250 Da).Here,we describe an analytical method using ultrahigh-performance liquid chromatography(UPLC)coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine *** experimental CCS values,along with mass spectral properties,were reported for the 174 *** experimental data included the mass-to-charge ratio(m/z),retention time(RT),tandem MS(MS/MS)spectra,and CCS *** the studied metabolites,263 traveling wave ion mobility spectrometry(TWIMS)-derived CCS values(TWCCSN2)were reported for the first time,and more than 70%of these were CCS values of *** TWCCSN2 values were highly repeatable,with inter-day variations of<1%relative standard deviation(RSD).The developed method revealed excellent TWCCSN2 accuracy with a CCS difference(DCCS)within±2%of the reported drift tube IMS(DTIMS)and TWIMS CCS *** complexity of the urine matrix did not affect the precision of the method,as evidenced by DCCS within±1.92%.According to the Metabolomics Standards Initiative,55 urinary metabolites were identified with a confidence level of *** these 55 metabolites,53(96%)were *** larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values,which clearly increased metabolite identification confidence.

关键词： Very low-molecular-weight metabolites Traveling wave ion mobility Collision cross-section Human urine

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

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Food Science and Human Wellness 2024年第4期13卷 2266-2276页

作者： Yu Ga Yuanyuan Wei Qingyu Zhao Yimeng Fan Yannan Zhang Zhifang Zhang Sijia Hao Lixia Wang Zhifen Wang Jinlong Han Shuang Wu Zhihui Hao Innovation centre of Chinese Veterinary medicine College of Veterinary MedicineChina Agricultural UniversityBeijing 100086China National Center of Technology Innovation for Medicinal Function of Food National Food and Strategic Reserves AdministrationBeijing 100193China Inner Mongolia Medical University Hohhot 010059China China Agricultural University Yantai Institute Yantai 264670China Shandong Academy of Agricultural Sciences Jinan 250100China

Ulcerative colitis(UC)is a common inflammatory disease of the gastrointestinal *** Chinese medicine(TCM)has long been used in Asia as a treatment for UC and Puerariae Radix(PR)is a reliable anti-diarrheal *** aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt(DSS)-induced UC model in mice and identify molecular mechanisms of PR *** chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identified potential PR and UC targets using a network pharmacology(NP)approach were obtained to guide mouse experiments.A total of 180 peaks were identified from PR including 48 flavonoids,46 organic acids,14 amino acids,8 phenols,8 carbohydrates,7 alkaloids,6 coumarins and 43 other *** results showed that caspase-1 was the most dysregulated of the core genes associated with UC.A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC *** also alleviated intestinal mucosal shedding,inflammatory cell infiltration and mucin *** treatment suppressed upregulation of NOD-like receptor protein 3(NLRP3),cysteinyl aspartate-specific proteases-1(caspase-1),apoptosis-associated speck-like(ASC)and gasdermin D(GSDMD)at both the protein and m RNA expression *** addition of a small molecule dual-specificity phosphatase inhibitor NSC 95397 inhibited the positive effects of *** results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 inflammasome activation in mice.

关键词： Puerariae Radix Ulcerative colitis molecular mechanisms Pyroptosis NOD-like receptor protein 3 inflammasome

Mitochondrial dysfunction:mechanisms and advances in therapy

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2362-2390页

作者： Yao Zong Hao Li Peng Liao Long Chen Yao Pan Yongqiang Zheng Changqing Zhang Delin Liu Minghao Zheng Junjie Gao centre for Orthopaedic Research Medical SchoolThe University of Western AustraliaNedlandsWA 6009Australia Department of Orthopaedics Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China Institute of Microsurgery on Extremities and Department of Orthopedic SurgeryShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell BiologyCAS Center for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Sixth People’s Hospital Fujian No.16Luoshan SectionJinguang RoadLuoshan StreetJinjiang CityQuanzhouFujianChina

Mitochondria,with their intricate networks of functions and information processing,are pivotal in both health regulation and disease ***,mitochondrial dysfunctions are identified in many common pathologies,including cardiovascular diseases,neurodegeneration,metabolic syndrome,and ***,the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to ***,these complexities do not prevent mitochondria from being among the most important therapeutic *** recent years,strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical *** intervention such as using healthy mitochondria to replenish or replace damaged mitochondria,has shown promise in preclinical trials of various *** components,including mtDNA,mitochondria-located microRNA,and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue ***,we review current knowledge of mitochondrial pathophysiology in concrete examples of common *** also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies,as well as the clinical translational situation of related pharmacology ***,this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

关键词： dysfunction injuries replace