RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge...RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge challenge.Herein,we report a novel furin-responsive small interfering RNA(siRNA)delivery vehicle with multiple functions for colorectal tumor treatment.A peptide-based siRNA delivery vehicle RVRR-P18-Gd,consisting of furin enzyme-specific peptide substrate Arg-Val-Arg-Arg(RVRR)with positive charge for siRNA binding,a Gd(III)chelated 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid(DOTA)(DOTA-Gd)for magnetic resonance imaging,and purpurin 18 as photosensitizer for photodynamic therapy(PDT),was rationally designed and synthesized.Taking advantage of the cationic amphiphilic feature,RVRR-P18-Gd molecules spontaneously self-assembled with negatively charged Hif-1αsiRNA into stable nanoparticles via attractive electrostatic interaction,which effectively prevented siRNA degradation by nucleases,prolonged the circulation half-life,and enhanced tumor accumulation.Moreover,the specific release of Hif-1αsiRNA mediated by endogenous furin significantly downregulated Hif-1αexpression in colorectal cancer cells,resulting in enhanced therapeutic susceptibility,and with the PDT effect,effectively suppressed HCT116 tumor growth in living mice.This work highlights a powerful and universal approach to precisely deliver siRNA to targeted tumors for efficient synergistic therapy.展开更多
The impact of cyclodextrins(CDs)on wine quality and stability remains largely unknown.This study systematically assessed the protective effect of the post-fermentation addition of CDs on color stability of red wine fr...The impact of cyclodextrins(CDs)on wine quality and stability remains largely unknown.This study systematically assessed the protective effect of the post-fermentation addition of CDs on color stability of red wine from the viewpoints of color characteristics,copigmentation and phenolic profiles.The grey relational analysis(GRA)and principal component analysis(PCA)methods were employed to dissect the key effective determinants related to color quality.The addition of CDs induced a significant hyperchromic effect of 8.19-25.40%,a significant bathochromic effect and an enhancement of the color intensity.Furthermore,the evolution of anthocyanin forms and the content of monomeric anthocyanins revealed that β-CD is a superior favorable cofactor during wine aging,but for long-term aging,2-HP-β-CD and 2-HP-γ-CD are more beneficial in promoting the formation of polymerized anthocyanins and color stability.This work provides an important reference for the use of CDs to enhance the color quality and stability of red wines.展开更多
Lung cancer is the most prevalent cancer in the world,and the main treatment for advanced non-small cell lung cancer is immunotherapy combined with chemotherapy.In recent years,bTMB has received increasing attention a...Lung cancer is the most prevalent cancer in the world,and the main treatment for advanced non-small cell lung cancer is immunotherapy combined with chemotherapy.In recent years,bTMB has received increasing attention as an emerging metric for monitoring the efficacy of tumour immunotherapy in terms of its operability,accessibility and real-time nature.We envisaged whether immunotherapy alone could be used to reduce the side effects of chemotherapy in patients with high bTMB lung cancer.We thus did a meta-analysis in order to show that immunotherapy alone is feasible in patients with high bTMB NSCLC.Methods This study aims to compare the efficacy of PD-1/PD-L1 inhibitors(namely,atezolizumab,pembrolizumab,nivolumab,or tislelizumab)versus chemotherapy in NSCLC patients.The search for relevant studies was conducted in three major databases(i.e.,PubMed,Embase,and Medline)up until January 2023.Specifically,we identified studies that reported risk ratios(HRs)for reporting progression-free survival(PFS)or overall survival(OS),or objective remission rates(ORs)for immunotherapy alone versus chemotherapy in high bTMB and low bTMB patient groups.Given that NSCLC represents the predominant type of lung cancer,we exclusively focused on this subtype.Our analysis encompassed a meta-analysis of the identified literature,incorporating heterogeneity analysis and sensitivity analysis.The quality of the evidence is evaluated using the Grading of Recommendations Assessment,Development and Evaluation(GRADE)approach to ascertain the reliability and robustness of the findings.Result-We conducted a meta-analysis of seven randomised controlled trials including 4,755 patients with advanced non-small cell lung cancer(NSCLC)evaluated the efficacy of PD-1 or PD-L1 monotherapy compared to chemotherapy alone.All patients were randomized to receive either PD-1/PD-L1 treatment alone or chemotherapy alone as a control.In the high bTMB patient group,PD-1/PD-L1 monotherapy resulted in significant improvements in overall survival(HR=0.55,95%CI 0.49–0展开更多
中国西部探明了一系列与新元古代以来幔源岩浆有关的镍铜铂族元素(platinum group elements,PGE)岩浆矿床,华北克拉通新元古代金川镍铜铂族硫化物矿床、峨眉山二叠纪大火成岩省金宝山铂族元素矿床等记录了不同构造环境幔源岩浆PGE超常...中国西部探明了一系列与新元古代以来幔源岩浆有关的镍铜铂族元素(platinum group elements,PGE)岩浆矿床,华北克拉通新元古代金川镍铜铂族硫化物矿床、峨眉山二叠纪大火成岩省金宝山铂族元素矿床等记录了不同构造环境幔源岩浆PGE超常富集成矿过程。亲铁性的铂族元素高度富集于地核,深部地幔起源、高程度部分熔融形成的镁铁质岩浆中PGE含量较高,地幔岩浆系统不同条件下铂族元素以纳米态元素簇、合金、硫化物熔体或超临界流体运移-聚集成矿,在阶段性岩浆房多阶段、多途径富集,成矿作用类型丰富。华北-华南克拉通岩石圈地幔PGE含量均略高于原始地幔值;华北克拉通岩石圈地幔PGE含量从古生代到中新生代略有降低,表明存在PGE抽取岩浆事件。中国西部新元古代以来的幔源岩浆源区PGE不亏损、岩浆活动时间长、岩浆-硫化物相互作用PGE多阶段富集及地幔柱岩浆动力学背景是PGE超常富集成矿的有利地质条件,其控制因素及动力学背景的认识对查明PGE成矿潜力和拓展资源储量具有重要意义。展开更多
上颌窦底提升术是解决上颌后牙区种植修复所需余留骨高度(residual bone height,RBH)不足时的常用治疗方法。目前,对于上颌窦内的成骨机制、上颌窦底提升术术式的选择、同期种植的时机、年龄或性别的影响、是否需要置入骨替代材料等问...上颌窦底提升术是解决上颌后牙区种植修复所需余留骨高度(residual bone height,RBH)不足时的常用治疗方法。目前,对于上颌窦内的成骨机制、上颌窦底提升术术式的选择、同期种植的时机、年龄或性别的影响、是否需要置入骨替代材料等问题众说纷纭。本文根据种植科团队有关上颌窦内成骨机制的研究成果,结合本院种植科10余年上颌窦底提升术的治疗效果,总结临床操作的方法与技巧,以期达到理论研究与临床实践相结合并最终指导临床的转化医学模式,提出了更加优化的、简单易行的上颌窦底提升术的方案与理念,即经牙槽嵴顶上颌窦底提升术+浓缩生长因子(concentrated growth factors,CGF)+同期植入种植体。展开更多
基金the National Science Foundation of China(grant no.22077092)the Open Project Program of the State Key Laboratory of Radiation Medicine and Protection(grant no.GZK1202140)+2 种基金Science and Technology Development Plan of Suzhou(grant no.SLJ2022018)Scientific Research Project of Suzhou Commission of Health(grant no.GSWS2020028)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘RNA interfering therapy has emerged as a promising therapeutic modality to treat cancer.The specific and efficient delivery of RNA into a tumor is crucial for achieving effective cancer gene therapy but remains a huge challenge.Herein,we report a novel furin-responsive small interfering RNA(siRNA)delivery vehicle with multiple functions for colorectal tumor treatment.A peptide-based siRNA delivery vehicle RVRR-P18-Gd,consisting of furin enzyme-specific peptide substrate Arg-Val-Arg-Arg(RVRR)with positive charge for siRNA binding,a Gd(III)chelated 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid(DOTA)(DOTA-Gd)for magnetic resonance imaging,and purpurin 18 as photosensitizer for photodynamic therapy(PDT),was rationally designed and synthesized.Taking advantage of the cationic amphiphilic feature,RVRR-P18-Gd molecules spontaneously self-assembled with negatively charged Hif-1αsiRNA into stable nanoparticles via attractive electrostatic interaction,which effectively prevented siRNA degradation by nucleases,prolonged the circulation half-life,and enhanced tumor accumulation.Moreover,the specific release of Hif-1αsiRNA mediated by endogenous furin significantly downregulated Hif-1αexpression in colorectal cancer cells,resulting in enhanced therapeutic susceptibility,and with the PDT effect,effectively suppressed HCT116 tumor growth in living mice.This work highlights a powerful and universal approach to precisely deliver siRNA to targeted tumors for efficient synergistic therapy.
基金supported by the Regional Collaborative Innovation Project in Xinjiang Autonomous Region of China(2022E02011)the National Key R&D Program of China(2019YFD1002500)the Key Project of Research and Development Plan in Ningxia Hui Autonomous Region of China(2018BBF02001)。
文摘The impact of cyclodextrins(CDs)on wine quality and stability remains largely unknown.This study systematically assessed the protective effect of the post-fermentation addition of CDs on color stability of red wine from the viewpoints of color characteristics,copigmentation and phenolic profiles.The grey relational analysis(GRA)and principal component analysis(PCA)methods were employed to dissect the key effective determinants related to color quality.The addition of CDs induced a significant hyperchromic effect of 8.19-25.40%,a significant bathochromic effect and an enhancement of the color intensity.Furthermore,the evolution of anthocyanin forms and the content of monomeric anthocyanins revealed that β-CD is a superior favorable cofactor during wine aging,but for long-term aging,2-HP-β-CD and 2-HP-γ-CD are more beneficial in promoting the formation of polymerized anthocyanins and color stability.This work provides an important reference for the use of CDs to enhance the color quality and stability of red wines.
文摘神经发展性障碍(Neurodevelopmental Disorders,NDDs)是指一系列困扰K12基础教育阶段儿童动作行为发展的精神障碍,其病因及发病机制仍不明确,尚无有效的预测诊疗手段。北京师范大学认知神经科学与学习国家重点实验室依托县/地/区级中心医院采集NDDs高发年龄段儿童脑智发育数据建立的“围产期因素下的多中心儿童脑智发展数据库(Multicenter Database on Perinatal Factors in Child Brain-Mind Development,PeriCBD)”,旨在建立围产期因素下3–10岁儿童脑智发育规律与个体差异相关数据信息平台,为全国脑智发展追踪队列研究、儿童NDDs预测诊疗提供重要基础数据。本文以在河南省安阳市妇幼保健院、重庆市梁平区人民医院已完成的数据采集工作为例,系统介绍PeriCBD组织框架,明确被试行为数据及磁共振成像数据的统一采集、清理、分析流程,数据抽取、转换、加载数据库链接等相关标准化流程,为后续PeriCBD数据采集及数据库使用建立范式。
基金supported by the Key Research and Development Project Institute of Hainan Province(ZDYF2023SHFZ117).
文摘Lung cancer is the most prevalent cancer in the world,and the main treatment for advanced non-small cell lung cancer is immunotherapy combined with chemotherapy.In recent years,bTMB has received increasing attention as an emerging metric for monitoring the efficacy of tumour immunotherapy in terms of its operability,accessibility and real-time nature.We envisaged whether immunotherapy alone could be used to reduce the side effects of chemotherapy in patients with high bTMB lung cancer.We thus did a meta-analysis in order to show that immunotherapy alone is feasible in patients with high bTMB NSCLC.Methods This study aims to compare the efficacy of PD-1/PD-L1 inhibitors(namely,atezolizumab,pembrolizumab,nivolumab,or tislelizumab)versus chemotherapy in NSCLC patients.The search for relevant studies was conducted in three major databases(i.e.,PubMed,Embase,and Medline)up until January 2023.Specifically,we identified studies that reported risk ratios(HRs)for reporting progression-free survival(PFS)or overall survival(OS),or objective remission rates(ORs)for immunotherapy alone versus chemotherapy in high bTMB and low bTMB patient groups.Given that NSCLC represents the predominant type of lung cancer,we exclusively focused on this subtype.Our analysis encompassed a meta-analysis of the identified literature,incorporating heterogeneity analysis and sensitivity analysis.The quality of the evidence is evaluated using the Grading of Recommendations Assessment,Development and Evaluation(GRADE)approach to ascertain the reliability and robustness of the findings.Result-We conducted a meta-analysis of seven randomised controlled trials including 4,755 patients with advanced non-small cell lung cancer(NSCLC)evaluated the efficacy of PD-1 or PD-L1 monotherapy compared to chemotherapy alone.All patients were randomized to receive either PD-1/PD-L1 treatment alone or chemotherapy alone as a control.In the high bTMB patient group,PD-1/PD-L1 monotherapy resulted in significant improvements in overall survival(HR=0.55,95%CI 0.49–0
文摘中国西部探明了一系列与新元古代以来幔源岩浆有关的镍铜铂族元素(platinum group elements,PGE)岩浆矿床,华北克拉通新元古代金川镍铜铂族硫化物矿床、峨眉山二叠纪大火成岩省金宝山铂族元素矿床等记录了不同构造环境幔源岩浆PGE超常富集成矿过程。亲铁性的铂族元素高度富集于地核,深部地幔起源、高程度部分熔融形成的镁铁质岩浆中PGE含量较高,地幔岩浆系统不同条件下铂族元素以纳米态元素簇、合金、硫化物熔体或超临界流体运移-聚集成矿,在阶段性岩浆房多阶段、多途径富集,成矿作用类型丰富。华北-华南克拉通岩石圈地幔PGE含量均略高于原始地幔值;华北克拉通岩石圈地幔PGE含量从古生代到中新生代略有降低,表明存在PGE抽取岩浆事件。中国西部新元古代以来的幔源岩浆源区PGE不亏损、岩浆活动时间长、岩浆-硫化物相互作用PGE多阶段富集及地幔柱岩浆动力学背景是PGE超常富集成矿的有利地质条件,其控制因素及动力学背景的认识对查明PGE成矿潜力和拓展资源储量具有重要意义。
文摘上颌窦底提升术是解决上颌后牙区种植修复所需余留骨高度(residual bone height,RBH)不足时的常用治疗方法。目前,对于上颌窦内的成骨机制、上颌窦底提升术术式的选择、同期种植的时机、年龄或性别的影响、是否需要置入骨替代材料等问题众说纷纭。本文根据种植科团队有关上颌窦内成骨机制的研究成果,结合本院种植科10余年上颌窦底提升术的治疗效果,总结临床操作的方法与技巧,以期达到理论研究与临床实践相结合并最终指导临床的转化医学模式,提出了更加优化的、简单易行的上颌窦底提升术的方案与理念,即经牙槽嵴顶上颌窦底提升术+浓缩生长因子(concentrated growth factors,CGF)+同期植入种植体。
