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Toward Selective Synthesis of Protein Olympiadanes via Orthogonal Active Templates in One Step

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CCS Chemistry 2024年第4期6卷 1047-1059页

作者： Fan Zhang Yajie Liu xiao-di Da Wen-Bin Zhang Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Chemistry and Physics of Ministry of EducationCenter for Soft Matter Science and EngineeringCollege of Chemistry and Molecular EngineeringPeking UniversityBeijing100871 Beijing Academy of Artificial Intelligence Beijing 100084

Unlike small molecules,the topological complexity of macromolecules remains largely unexplored due to the huge synthetic ***,we report the development of orthogonal active templates for concise and selective synthesis of protein[n]heterocatenanes toward protein *** active template(AT-Snoop)was first developed based on the isopeptide-bond-forming RrgA domain with comparable efficiency and excellent orthogonality to the previously reported active template(AT-Spy)based on the CnaB2 *** combination facilitated the selective synthesis of protein[n]catenanes from multiple components in one step and the resulting structures were verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis,size exclusion chromatography,liquid chromatography-mass spectrometry,and proteolytic digestion *** results offered a promising solution to tackling the daunting challenge of precision synthesis of protein olympiadane with five distinct ring *** only did the success provide new tools forproteintopologyengineeringbutalsospurred and fueled the future exploitation of topology-related functional benefits in protein science.

关键词： catenane topology active template SnoopTag SnoopCatcher SpyTag SpyCatcher

Lenvatinib combined with sintilimab plus transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma

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World Journal of Clinical Cases 2024年第2期12卷 285-292页

作者： Sha-Sha Sun xiao-di Guo Wen-Dong Li Jing-Long Chen Department of Oncology Capital Medical University Affiliated Beijing Ditan HospitalBeijing 100015China

BACKGROUND Recently,combination therapy has shown a better trend towards improved tumour response and survival outcomes than monotherapy in patients with hepatocellular carcinoma(HCC).However,research on triple therapy[lenvatinib+sintilimab+transarterial chemoembolization(TACE)]as a first-line treatment for advanced HCC is *** To evaluate the safety and efficacy of triple therapy as a first-line treatment for advanced *** HCC patients with Barcelona Clinic Liver Cancer stage C treated with triple therapy were *** patients were treated with lenvatinib every day and sintilimab once every 3 ***,TACE was performed every 4-6 wk if *** primary outcome of the study was overall survival(OS).The secondary outcomes were the objective response rate(ORR),disease control rate(DCR),and incidence of adverse *** Forty HCC patients who underwent triple therapy were retrospectively analysed from January 2019 to January *** a median follow-up of 8.5 months,the 3-,6-,and 12-mo OS rates were 100%,88.5%,and 22.5%,*** ORR and DCR were 45%and 90%,*** median progressive free survival and median OS were not *** complications were observed in 76%of the patients(grade 3,15%;grade 4,2.5%).CONCLUSION Combination therapy comprising lenvatinib,sintilimab and TACE achieved promising outcomes in advanced HCC patients and had manageable effects.

关键词： Lenvatinib Sintilimab Advanced hepatocellular carcinoma Combination therapy Tumor response

Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress

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Chinese Journal of Integrative Medicine 2024年第5期30卷 398-407页

作者： JI xiao-di YANG ding CUI Xi-yuan LOU Li-xia NIE Bo ZHAO Jiu-li ZHAO Ming-jing WU Ai-ming Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine Key Laboratory of Chinese Internal Medicine of Ministry of Education and BeijingBeijing 100700China Department of Traditional Chinese Medicine Fuwai HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China

Objective:To investigate the pharmacological mechanism of Qili Qiangxin Capsule(QLQX)improvement of heart failure(HF)based on miR133a-endoplasmic reticulum stress(ERS)***:A left coronary artery ligation-induced HF after myocardial infarction model was used in this *** were randomly assigned to the sham group,the model group,the QLQX group[0.32 g/(kg·d)],and the captopril group[2.25 mg/(kg·d)],15 rats per group,followed by 4 weeks of *** function such as left ventricular ejection fraction(EF),fractional shortening(FS),left ventricular systolic pressure(LVSP),left ventricular end diastolic pressure(LVEDP),the maximal rate of increase of left ventricular pressure(+dp/dt max),and the maximal rate of decrease of left ventricular pressure(–dp/dt max)were monitored by echocardiography and *** and eosin(HE)and Masson stainings were used to visualize pathological changes in myocardial *** m RNA expression of mi R133a,glucose-regulated protein78(GRP78),inositol-requiring enzyme 1(IRE1),activating transcription factor 6(ATF6),X-box binding protein1(XBP1),C/EBP homologous protein(CHOP)and Caspase 12 were detected by *** protein expression of GRP78,p-IRE1/IRE1ratio,cleaved-ATF6,XBP1-s(the spliced form of XBP1),CHOP and Caspase 12 were detected by Western *** T-mediated d UTP nick-end labeling(TUNEL)staining was used to detect the rate of ***:QLQX significantly improved cardiac function as evidenced by increased EF,FS,LVSP,+dp/dt max,-dp/dt max,and decreased LVEDP(Pdiac pathologic damage to some *** staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue(P<0.01).Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of mi R133a and inhibited the m RNA expressions of GRP78,IRE1,ATF6 and XBP1,as well as decreased the protein expressions of GRP78,cleave

关键词： heart failure Qili Qiangxin Capsule miR133a endoplasmic reticulum stress apoptosis

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质谱技术在核酸检测分析中的研究进展

中华预防医学杂志 2024年第1期58卷 98-106页

作者：赵欣肖迪传染病溯源预警与智能决策全国重点实验室、中国疾病预防控制中心传染病预防控制所北京102206

质谱技术是一种基于质谱仪设备检测物质分子量的谱学技术方法。质谱类型众多、功能各异,在各个学科领域中广泛用于科学研究与应用技术开发。近年来,质谱技术在核酸检测分析中显现出巨大的潜力,尤其是基于基质辅助激光解吸电离飞行时间... 详细信息

质谱技术是一种基于质谱仪设备检测物质分子量的谱学技术方法。质谱类型众多、功能各异,在各个学科领域中广泛用于科学研究与应用技术开发。近年来,质谱技术在核酸检测分析中显现出巨大的潜力,尤其是基于基质辅助激光解吸电离飞行时间质谱的核酸检测分析技术,因其快速、高通量、准确等特性而成为研究热点。采用质谱技术进行核酸研究,突出表现在对单核苷酸多态性、基因突变、DNA甲基化及DNA拷贝数变异的检测分析。本文对质谱技术在核酸检测中的研究与应用进行阐述,以期为基于质谱的新型核酸检测技术的开发与应用提供参考。

关键词：质谱 DNA甲基化单核苷酸多态性 DNA拷贝数变异多重PCR-质谱微测序

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 304-310页

作者： Yuan-Zhang Zhu Zhi-Zhi Dou Wen-Ying Wang Qing-Yue Ma Wen-Dan Yi Ning-Ning Yao Yi-Chong Liu xiao-di Gao Qian Zhang Wen-Juan Luo Department of Ophthalmology the Affiliated Hospital of Qingdao UniversityQingdao 266000Shandong ProvinceChina

AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were *** patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum *** coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)*** macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were ***:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during *** 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,***:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.

关键词： conbercept diabetic nephropathy diabetic macular edema optical coherence tomography

兼顾通信效率与效用的自适应高斯差分隐私个性化联邦学习

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计算机学报 2024年第4期47卷 924-946页

作者：李敏肖迪陈律君重庆大学计算机学院重庆400044

近年来,由于联邦学习中的通信参数(或梯度)会给参与方本地敏感数据带来重大的隐私泄露风险,联邦学习隐私保护引起了广泛的关注.然而,梯度交换频繁、数据分布异构、参与方本地硬件资源受限等一系列不可避免的因素给联邦学习隐私保护增加... 详细信息

近年来,由于联邦学习中的通信参数(或梯度)会给参与方本地敏感数据带来重大的隐私泄露风险,联邦学习隐私保护引起了广泛的关注.然而,梯度交换频繁、数据分布异构、参与方本地硬件资源受限等一系列不可避免的因素给联邦学习隐私保护增加了挑战难度.为了以一种统一的方式同时有效地解决数据隐私、模型效用、通信效率以及参与方数据非独立同分布等四个方面的问题,本文提出了一种新的兼顾通信效率与效用的自适应高斯差分隐私个性化联邦学习(Communication-efficient and Utility-aware Adaptive Gaussian differential Privacy for Personalized Federated Learning,CUAG-PFL)方法.具体而言,本文提出一种动态层级压缩模型梯度的方案先为通信模型梯度每一层动态生成特定的压缩率,再根据压缩率构造对应的确定性二进制测量矩阵去除梯度冗余信息.随后,通过同时优化裁剪阈值、敏感度和噪声尺度等隐私相关参数来对压缩的模型梯度执行自适应高斯差分隐私操作.此外,本文对CUAG-PFL进行了严格的隐私分析.为了验证CUAG-PFL在隐私、效用、通信效率以及个性化四个方面的优势,本文在CIFAR-10和CIFAR-100两个真实联邦数据集上进行了大量实验模拟、对比和分析,结果表明CUAG-PFL能够提高参与方本地数据隐私性、通信效率和模型效用,同时解决了数据非独立同分布的问题.特别地,即使在隐私预算仅为0.92且上行通信量减少68.6%时,CUAG-PFL因隐私保护和梯度压缩所引起的模型效用损失仅为1.66%.

关键词：自适应高斯差分隐私隐私-效用权衡动态层级压缩通信高效个性化联邦学习隐私计算

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营商环境生态驱动制造业智能化的组态路径研究

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科学学研究 2024年第4期42卷 746-756页

作者：李晓娣原媛哈尔滨工程大学经济管理学院黑龙江哈尔滨150001

制造业智能化是建设制造强国和培育产业竞争新优势的重要推动力。如何优化营商环境促进制造业智能化发展是亟需解决的重要问题。本文基于组态视角,采用NCA与QCA相结合的研究方法,以我国30个省份作为研究样本,探究营商环境生态对制造业... 详细信息

制造业智能化是建设制造强国和培育产业竞争新优势的重要推动力。如何优化营商环境促进制造业智能化发展是亟需解决的重要问题。本文基于组态视角,采用NCA与QCA相结合的研究方法,以我国30个省份作为研究样本,探究营商环境生态对制造业智能化的多样化驱动路径。研究发现:单个营商环境条件并非是产生高制造业智能化的必要条件,高制造业智能化受到政务环境、市场环境、创新环境、金融服务、公共服务、人力资源共六个条件的“多重并发”影响,形成了三条组态路径,具体归纳为金融与资源驱动型、市场助力下依托创新环境的资源驱动型、政府主导下的创新驱动型。通过进一步探究研究样本的空间情境差异可知,发达地区和欠发达地区实现制造业智能化的驱动路径具有明显的差异性。

关键词：营商环境生态制造业智能化必要条件分析(NCA) 模糊集定性比较分析(fsQCA) 组态路径

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Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism

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World Journal of Hepatology 2024年第2期16卷 264-278页

作者： Hao Ouyang Hui Miao Zhen Li Duan Wu Si-Cheng Gao Yao-Yao Dai xiao-di Gao Hai-Sheng Chai Wei-Ye Hu Jun-Feng Zhu Department of Liver Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 201203China State Key Laboratory of Bioreactor Engineering East China University of Science and TechnologyShanghai 201203China

BACKGROUND Liver fibrosis is a formidable global medical challenge,with no effective clinical treatment currently *** granule(YHG)is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae *** is frequently used for upper respiratory tract infections,pharyngitis,as well as acute and chronic *** To investigate the potential of YHG in alleviating carbon tetrachloride(CCl4)-induced liver fibrosis in *** To induce a hepatic fibrosis model in mice,this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 ***,liver fibrosis mice in the low dose of YHG(0.4 g/kg)and high dose of YHG(0.8 g/kg)groups were orally administered YHG once a day for 4 *** alanine/aspartate aminotransferase(ALT/AST)activity and liver hydroxyproline content were *** red and Masson's trichrome staining assay were *** polymerase chain reaction,western-blot and enzyme-linked immunosorbent assay were *** glutathione content,superoxide dismutase activity level,reactive oxygen species and protein carbonylation amount were *** The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice,as reflected by decreased serum ALT/AST activity and improved liver histological *** also attenuated liver fibrosis,evident through reduced liver hydroxyproline content,improvements in Sirius red and Masson's trichrome staining,and lowered serum hyaluronic acid ***,YHG hindered the activation of hepatic stellate cells(HSCs)and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated *** prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2(Nrf2)and upregulated the expression of Nrf2-dependent downstream antioxidant *** addition,YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice,as demonstrated by increased liver adenosine triphosphate content,

关键词： Yinhuang granule Liver fibrosis Hepatic stellate cells Oxidative injury Nuclear factor erythroid 2-related factor 2 Inflammation

Advanced hepatocellular carcinoma in a patient with neurofibromatosis type 1 and malignant peripheral nerve sheath tumor

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Hepatobiliary & Pancreatic diseases International 2024年第5期23卷 530-532页

作者： Ahmad Alhaskawi Yan-Zhao Dong xiao-di Zou Sohaib Hasan Abdullah Ezzi Ze-Wei Wang Hai-Ying Zhou Sahar Ahmed Abdalbary Hui Lu Department of Orthopedics the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Chinese Medicine the Second Affiliated HospitalZhejiang Chinese Medical UniversityHangzhou 310005China Department of Orthopedics the Third Xiangya HospitalCentral South UniversityChangsha 410083China Zhejiang University School of Medicine Hangzhou 310000China Department of Orthopedic Physical Therapy Faculty of Physical TherapyNahda University in Beni SuefBeni SuefEgypt

To the Editor: Neurofibromatosis type 1(NF-1), or Von Recklinghausen disease, is a genetic disorder inherited in an autosomal dominant pattern. It is caused by a mutation in the neurofibromin gene located on chromosome 17, accounting for 96% of all neurofibromatosis cases. This condition can affect multiple systems and often leads to the formation of tumors along the nervous system [1]. Patients with NF-1 may exhibit various symptoms, including Lisch nodules, neurofibromas, scoliosis, café au lait spots, learning disabilities, vision disorders, and epilepsy.

关键词： epilepsy hepatocellular malignant