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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin Li Qianfeng Zhang Zhiqian Li Long Ren Dayi Pan Qiyong Gong Zhongwei Gu hao cai Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

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Ultrahigh strength and uniform corrosion in Zn-Li alloys through ultrahigh pressure supersaturated solid solution treatment for biodegradable orthopedic applications

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Rare Metals 2024年第10期43卷 5284-5304页

作者： Wan-Ying Li Yi-Long Dai Wen-hao cai Si-Han Lin Lin Guo De-Chuang Zhang Yuncang Li Cuie Wen School of Materials Science and Engineering Xiangtan University Department of Prosthodontics Shanghai Ninth People′s HospitalShanghai Jiao Tong University Key Laboratory of Low Dimensional Materials&Application Technology Ministry of EducationXiangtan University School of Engineering RMIT UniversityMelbourne

Zn-Li alloys are considered promising candidate materials for biodegradable orthopedic implant applications due to their high mechanical performance and good ***,the presence of a large number of second-phase particles in this class of Zn alloys can lead to severe localized degradation due to micro-galvanic corrosion,which is detrimental to the mechanical integrity of the alloys during tissue healing in the human *** this study we report ultrahigh strength,uniform corrosion,good cytocompatibility,and effective antibacterial ability in Zn-x Li（x=0.3,0.5,0.7;wt%） alloys achieved through supersaturated solid solution treatment （SSST） at 375℃ under ultrahigh pressure of 3 GPa.A high concentration of β-LiZn4phases coexisted with the-Zn matrix in the as-cast Zn-x Li alloys,whereas almost all the Li dissolved into the-Zn matrix of SSST *** yield strength was 437 MPa for SSST Zn-0.3Li,592 MPa for SSST Zn-0.5 Li and 686 MPa for SSST *** SSST Zn-Li alloys showed uniform degradation with remarkably reduced degradation rates compared to their as-cast *** 25% concentration extracts of the Zn-x Li alloys demonstrated no cytotoxicity toward MC3T3-E1 cells,and the alloys exhibited effective antibacterial ability agains methicillin-resistant staphylococcus aureus.

关键词： Corrosion behavior Mechanical property Supersaturated solid solution treatment (SSST) Ultrahigh pressure Zn-Li alloy

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Lysosome-targeted carbon dots with a light-controlled nitric oxide releasing property for enhanced photodynamic therapy

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Chinese Chemical Letters 2024年第4期35卷 420-425页

作者： hao cai Xiaoyan Wu Lei Jiang Feng Yu Yuxiang Yang Yan Li Xian Zhang Jian Liu Zijian Li Hong Bi School of Materials Science and Engineering Anhui UniversityHefei 230601China School of Chemistry and Chemical Engineering Anhui UniversityHefei 230601China School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China

The reactive oxygen species(ROS) generation efficiency is always limited by the extreme tumor microenvironment(TME), leading to unsatisfactory antitumor effects in photodynamic therapy(PDT). As a promising gas therapy molecule, nitric oxide(NO) is independent of oxygen and could even synergize ROS to enhance the therapeutic effect. However, the short half-life, instability, and uncontrollable release of exogenous NO limited the application of tumor synergistic therapy. Herein, we reported a novel kind of red-emissive carbon dots(CDs) that was capable of lysosome-targeted and light-controlled NO delivery. The CDs were synthesized by using metformin and methylene blue(MB) via a hydrothermal *** obtained metformin-MB CDs(MMCDs) exhibited a higher1O2quantum yield and NO generation efficiency under light emitting diode(LED) light irradiation. Noteworthily, the1O2could further in situ oxidize NO into peroxynitrite anions(ONOO-), which own the higher cytotoxicity against cancer *** experiments indicate that MMCDs could destruct lysosome membrane integrity and kill almost 80%of Hep G2 cells under light irradiation while very low cytotoxicity in the dark. Moreover, MMCDs significantly decreased tumor volume and weight after phototherapy in hepatoma Hep G2-bearing mice. Our study provides a new strategy for light-controlled NO generation as well as precise lysosome-targeting for enhancement of PDT efficiency.

关键词： Carbon dots Nitric oxide Lysosome-targeting Photodynamic therapy Cancer

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Follow-up study of gallbladder stones in 44 children

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World Journal of Clinical Cases 2024年第18期12卷 3403-3409页

作者： Jian-Xiong Yu Zhi-Zhong Jiang Yuan-hao cai Lin Zhou Bin cai Department of Pediatric The Firs Affiliated Hospital of Naval Medical UniversityShanghai 20000China

BACKGROUND Cholesterol stones affect a certain subpopulation of *** have been raised on the impact of gallbladder surgery on the growth of children and *** To study the population characteristics,clinical features,treatment,and prognosis of gallstones in *** The clinical data of 44 children with gallstones admitted to The First Affiliated Hospital of Naval Medical University from August 2009 to August 2021 were collected,the children were followed up by telephone to monitor their *** follow-up ended in August *** shortest follow-up time was 2 years and 6 months,whereas the longest was 13 years and 11 *** population characteristics,general clinical characteristics,and treatments were retrospectively *** children were divided according to whether they underwent surgical gallbladder removal into an operation group(n=28)and a non-operation group(n=16),The effects of surgical gallbladder resection on the growth and development of children were *** The male–female ratio in the population was 6:5 and 84.09%of the children had onset in ***,29.55%of the children were overweight or *** study identified 26 cases with metabolic abnormalities,9 with hemolytic anemia,and 4 with choledochal *** the population,68.18%had recurrent symptomatic *** treatment accounted for 63.64%,with laparoscopic cholecystectomy accounting for 71.43%of surgical *** significant differences were observed in symptoms and complications between the surgery and non-surgery ***,no significant differences were found between the two groups in the attainment of genetic height target and the rightward shift of height curve during *** The sex characteristics of gallstones in children were not *** gallstones occurred in adolescents and rarely in young children.A considerable proportion of children have inborn causes,which are of

关键词： Gallstones in children Clinical characteristics Growth and development Operation Clinical features

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Prognostic value of neutrophil-to-lymphocyte ratio in end-stage liver disease:A meta-analysis

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World Journal of Hepatology 2024年第3期16卷 477-489页

作者： Xiang-hao cai Yun-Ming Tang Shu-Ru Chen Jia-Hui Pang Yu-Tian Chong Hong Cao Xin-Hua Li Department of Infectious Disease Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated ***,some studies have contested the prognostic value of NLR in *** To investigate the ability of NLR to predict *** Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with *** sizes were calculated using comprehensive meta-analysis software and SATAT *** A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the *** the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced *** Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian *** is a useful prognostic biomarker in patients with ESLD.

关键词： Neutrophil-to-lymphocyte ratio End stage liver diseases Prognosis Meta-analysis Mortality

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采用新兴隧穿器件的低功耗微控制器设计与实现

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电子与信息学报 2024年第5期46卷 2264-2273页

作者：蔡浩童辛芳杨军东南大学集成电路学院南京210096

基于隧穿场效应晶体管(TFET)器件的低功耗微控制器设计将器件、电路和系统结合,利用具有超低亚阈值摆幅特性的器件使得电路在非工作情况下达到极低泄露功耗,避免了金属氧化物半导体场效应晶体管(MOSFET)器件亚阈值摆幅理论极限带来的功... 详细信息

基于隧穿场效应晶体管(TFET)器件的低功耗微控制器设计将器件、电路和系统结合,利用具有超低亚阈值摆幅特性的器件使得电路在非工作情况下达到极低泄露功耗,避免了金属氧化物半导体场效应晶体管(MOSFET)器件亚阈值摆幅理论极限带来的功耗瓶颈,解决了目前对电池供电设备中微控制器的低功耗需求问题。TFET器件与传统MOSFET器件在工作机理上差异较大,主要体现在关断后具有更低的泄露电流,可以在更低的电压下工作,适用于长休眠电池供电低功耗需求下的物联网应用场景设计。该文调研了近年来TFET器件在低功耗电路设计方面的研究,介绍了传统微控制器的结构以及功耗来源,同时阐述了TFET器件的工作原理、特性以及设计挑战,在数字电路、模拟电路以及系统设计各领域考察了TFET器件的研究发展进程,并对各设计方案进行了优劣势分析,结合文献调研分析了TFET器件在低功耗微控制器设计领域的未来展望。

关键词：物联网低功耗微控制器新型隧穿器件

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Megafossils of Betulaceae from the Oligocene of Qaidam Basin and their paleoenvironmental and phytogeographic implications

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Plant Diversity 2024年第1期46卷 101-115页

作者： Tao Yang Jia-hao cai Yan-Zhi Dai Hong-Yu Chen Lei Han Li Zhang Wei-Yu Liang Xu-Jun Li Wen-Jia Li Jing-Yu Wu San-Ping Xie De-Fei Yan School of Earth Sciences and Key Laboratory of Mineral Resources in Western China(Gansu Province) Lanzhou UniversityLanzhou 730000China Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China State Key Laboratory of Palaeobiology and Stratigraphy Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and PaleoenvironmentChinese Academy of SciencesNanjing 210008China Center for Research and Education on Biological Evolution and Environments School of Earth Sciences and EngineeringNanjing UniversityNanjing 210023China

Understanding the paleoenvironment and phytogeographical history of the Tibetan Plateau,China relies on discovering new plant *** Qaidam Basin has long been regarded as an ideal‘field laboratory’to investigate the paleoclimate and paleobiological evolution of the northern Tibetan ***,fossil angiosperms from the Qaidam Basin are rare,and our knowledge of its paleovegetation is ***,we report fossil leaves and fruits of Betulaceae found from the Oligocene Shangganchaigou Formation of northwestern Qaidam Basin(Huatugou area).Comparative morphological analysis led us to assign the fruits to the Betula subgenus Betula and the leaves to Carpinus *** findings,together with other reported fossil plants from the same locality,reveal a close floristic linkage between the Qaidam Basin and Europe during the *** northern pathway of this floristic exchange may have crossed through the Qaidam Basin during the late *** floristic linkage may have been facilitated by the continuous narrowing of the Turgai Strait and stronger westerlies,which transported moisture and provided favorable climatic ***,fossil plants collected from the Qaidam Basin suggest that during the Oligocene this region had warm and humid deciduous broad-leaf forest,which differs from the region’s modern vegetation and indicates that the Qaidam Basin may have been a suitable region for these plants to flourish and spread during the Oligocene.

关键词： Paleoenvironment Biogeography Betulaceous fossil Qaidam basin Tibetan Plateau Oligocene

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64排螺旋CT检查诊断肺小结节及早期肺癌的价值

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常州实用医学 2024年第2期40卷 85-89页

作者：蔡昊常州市第二人民医院影像科江苏常州213003

目的分析64排螺旋CT检查诊断肺小结节及早期肺癌的价值。方法选择本院2018年12月-2019年12月确诊为肺小结节及早期肺癌患者60例,随机分成常规组和实验组,每组30例。常规组采用常规CT技术扫描,实验组采用64排螺旋CT检查,比较两组CT扫描... 详细信息

目的分析64排螺旋CT检查诊断肺小结节及早期肺癌的价值。方法选择本院2018年12月-2019年12月确诊为肺小结节及早期肺癌患者60例,随机分成常规组和实验组,每组30例。常规组采用常规CT技术扫描,实验组采用64排螺旋CT检查,比较两组CT扫描技术获得的图像质量、胸部CT扫描耗时、胸部CT扫描技术的术前检查与术后病理检查结果符合率、胸部CT扫描技术术前检查的误诊率与漏诊率。结果CT扫描图像质量优良率实验组明显高于常规组,差异有统计学意义(P0.05)。结论64排螺旋CT用于诊断肺小结节及早期肺癌具有一定优势,能够有效提高图像质量,缩短检查时间,提高诊断率。

关键词： 64排螺旋CT 肺小结节早期肺癌诊断价值

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超高分子量聚α-烯烃的高效合成及其减阻性能研究

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高分子学报 2024年第4期55卷 419-427页

作者：姜子豪李鑫源回立为康宇泽王菲蔡浩潘莉李悦生天津大学材料科学与工程学院天津300350 廊坊开发区中油科新化工有限责任公司廊坊065000

利用第四代Ziegler-Natta催化体系——负载在MgCl_(2)上的TiCl_(4)为主催化剂,三乙基铝(Et_(3)Al)为助催化剂,甲基环己基二甲氧基硅烷(CHMDMS)为外给电子体,在磁力搅拌和机械搅拌2种条件下催化1-辛烯和1-癸烯共聚合,制得了一系列高减阻... 详细信息

利用第四代Ziegler-Natta催化体系——负载在MgCl_(2)上的TiCl_(4)为主催化剂,三乙基铝(Et_(3)Al)为助催化剂,甲基环己基二甲氧基硅烷(CHMDMS)为外给电子体,在磁力搅拌和机械搅拌2种条件下催化1-辛烯和1-癸烯共聚合,制得了一系列高减阻性能聚α-烯烃(Poly-alpha-olefin,PAO)类减阻剂.利用高温凝胶渗透色谱仪测得聚合物的重均分子量(M_(w))在3×10^(6)以上,分子量分布指数(PDI)基本在3.04以内.进一步通过低温机械搅拌可实现更窄的聚合物分子量分布(1.27~1.90).通过核磁共振(^(13)C-NMR)对聚合物进行分子结构表征,结果表明得到了目标产物、无单体残留,且聚合物中单体比例与投料比基本一致.示差扫描量热法(DSC)和X射线衍射(XRD)测试结果表明,成功合成了无结晶行为的聚合物.热重分析(TGA)结果表明,该聚合物在氮气气氛下的热分解温度在300℃以上,远高于使用温度.环路管道循环实验表明,随着聚合物分子量增加,减阻效率整体呈增加趋势,共聚物的减阻效率大于均聚物;随着单体与催化剂的摩尔比增加,减阻效率先升高后降低.相较已有报道,减阻性能有较大提升,最高减阻率可达50%.

关键词：减阻剂聚α-烯烃减阻率 Ziegler-Natta催化剂

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基于指纹图谱和化学计量学的白芍不同炮制品成分差异研究

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世界中医药 2024年第14期19卷 2048-2054页

作者：任娟刘晓李伟东蔡皓蔡宝昌南京中医药大学附属医院南京210009 南京中医药大学南京210023 南京海源中药饮片有限公司南京210061

目的:采用高效液相色谱法(HPLC)指纹图谱技术结合化学计量学的分析方法,探究白芍不同炮制品的化学成分差异性,筛选差异标志物,为建立白芍及其炮制品质量标准提供参考。方法:建立白芍不同炮制品HPLC指纹图谱,采用中药色谱指纹图谱相似度... 详细信息

目的:采用高效液相色谱法(HPLC)指纹图谱技术结合化学计量学的分析方法,探究白芍不同炮制品的化学成分差异性,筛选差异标志物,为建立白芍及其炮制品质量标准提供参考。方法:建立白芍不同炮制品HPLC指纹图谱,采用中药色谱指纹图谱相似度评价系统计算相似度,标定共有峰并进行指认及归属;采用多元统计分析筛选出白芍不同炮制品的差异性标志物。结果:生、炒、酒白芍指纹图谱相似度均>0.900,不同白芍炮制品共标定17个共有峰,指认并归属7个成分;分层聚类分析(HCA)和主成分分析(PCA)结果可将生、炒、酒白芍明显区分;正交偏最小二乘法判别分析(OPLS-DA)结果表明,1,2,3,4,6-五没食子酰葡萄糖、没食子酸、芍药苷是生、酒白芍的主要差异性标志物,没食子酸、芍药苷、1,2,3,4,6-五没食子酰葡萄糖、1个未知成分和芍药新苷是生、炒白芍的主要差异性标志物。结论:1,2,3,4,6-五没食子酰葡萄糖、没食子酸、芍药苷和芍药新苷可作为白芍不同炮制品的质量标准研究指标成分。

关键词：白芍炮制指纹图谱分层聚类分析主成分分析正交偏最小二乘法判别分析

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