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Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses

Signal Transduction and Targeted Therapy 2024年第4期9卷 1768-1776页

作者： Hang Chi Suo-Qun Zhao Ru-Yi Chen Xing-Xing Suo Rong-Rong Zhang Wen-Hui Yang Dong-Sheng Zhou Min Fang bo Ying Yong-Qiang Deng cheng-Feng Qin State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAMMS100071BeijingChina College of Life Sciences Inner Mongolia Agricultural UniversityHohhot010018Inner MongoliaChina School of Life Sciences Henan UniversityKaifeng475004HenanChina Suzhou Abogen Biosciences Co. LtdSuzhou215123JiangsuChina Research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical Sciences100071BeijingChina

The Orthopoxvirus genus,especially variola virus(VARV),monkeypox virus(MPXV),remains a significant public health threat *** development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing ***-encoded antibodies have emerged as a powerful and universal platform for rapid antibody ***,by using the established lipid nanoparticle(LNP)-encapsulated mRNA platform,we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against *** vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing *** importantly,mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus(VACV)lethal challenge mouse model,and a unique mRNA antibody cocktail,Mix2a,exhibited superior in vivo protection by targeting both intracellular mature virus(IMV)-form and extracellular enveloped virus(EEV)-form *** summary,our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform,highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as otheremerging viruses.

关键词： proof universal neutral

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NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 153-164页

作者： bo Shi cheng-Jie Lyu Zhen-Kai Le Hao-Sen Ji Yi Xiao Yuan-Yuan Zhang Shou-Jiang Huang Lin-Jun Yu Qiang Shu Jin-Fa Tou Deng-Ming Lai Department of Neonatal Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Thoracic and Cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China

Background Macrophages are involved in various immune inflammatory disease *** study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western *** pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of *** mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various ***,intestinal epithelial cell injuries,and IL-1β release were *** Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β ***,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC ***3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell *** Macrophage activation may be essential for NEC ***3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

关键词： Caspase-1 Interleukin-1β Macrophage Necrotizing enterocolitis NLRP3

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Efficacy and safety of bilastine *** for the treatment of chronic idiopathic urticaria:A multicenter,double-blind,double-dummy,phase III,non-inferiority,randomized clinical trial

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Chinese Medical Journal 2024年第12期137卷 1480-1482页

作者： Xue Chen Xiuping Han bo cheng Hui Li Lingling Liu Songmei Geng Linfeng Li Jie Li Qing Guo Guoyi Zhang Hong Fang Jianzhong Zhang Department of Dermatology Peking University People’s HospitalBeijing 100044China Department of Dermatology Shengjing Hospital of China Medical UniversityShenyangLiaoning 110055China Department of Dermatology The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350004China Department of Dermatology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Dermatology Peking University First HospitalBeijing 100034China Department of Dermatology The Second Affiliated Hospital of Xi’an Jiaotong University(Xibei Hospital)Xi’anShaanxi 710006China Department of Dermatology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan 410008China Department of Dermatology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouGuangdong 510120China Department of Dermatology Hospital for Skin DiseasesChinese Academy of Medical SciencesNanjingJiangsu 210042China Department of Dermatology The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

To the Editor:Chronic urticaria,prevalent globally and increasing in China,predominantly affects young and middle-aged women,impacting their quality of life(QoL).[1]Standard treatment involves second-generation H1 antihistamines,with bilastine showing promise due to its selective action and minimal side ***,direct comparative studies are scarce,particularly in the Chinese *** aimed to evaluate the efcacy and safety of bilastine compared to levocetirizine in Chinese patients.

关键词： treatment double globally

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Thermodynamics of charged black holes in Maxwell-dilaton-massive gravity

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Chinese Physics C 2024年第7期48卷 232-243页

作者：岳瑞宏钱凯强刘博邹德成 Center for Gravitation and Cosmology College of Physical Science and TechnologyYangzhou UniversityYangzhou 225009China School of Physics Northwest UniversityXi'an 710127China School of Physics and Information Science Shaanxi University of Science and TechnologyXi'an 710021China College of Physics and Communication Electronics Jiangxi Normal UniversityNanchang 330022China

Considering the nonminimal coupling of the dilaton field to the massive graviton field in Maxwelldilaton-massive gravity,we obtain a class of analytical solutions of charged black holes,which are neither asymptotically flat nor(A)*** calculated thermodynamic quantities,such as mass,temperature,and entropy,verify the validity of the first law of black hole ***,we further investigate the critical behaviors of these black holes in the grand canonical and canonical ensembles and find a novel critical phenomenon never before observed,known as the"reverse"reentrant phase transition with a tricritical *** implies that the system undergoes a novel"SBH-LBH-SBH"phase transition process and is the reverse of the"LBH-SBH-LBH"process observed in reentrant phase transitions.

关键词： Maxwell-dilaton-massive gravity charged black hole reverse reentrant phase transition VdW-like phase transitions

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近断层地震动作用下浅埋综合管廊地震易损性研究

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工程力学 2024年第2期41卷 213-221页

作者：张海王程西王岱刘中宪孟思博天津市土木建筑结构防护与加固重点实验室天津300384 天津城建大学土木工程学院基础设施防护和环境绿色生物技术国际联合研究中心天津300384

为准确评估近断层地震动作用下浅埋综合管廊的地震损伤,利用ABAQUS建立土-结构整体有限元模型,以综合管廊层间位移角最大值为损伤指标,基于IDA方法进行结构地震易损性分析,重点考察近断层地震动强度指标和场地土特性对综合管廊抗震性能... 详细信息

为准确评估近断层地震动作用下浅埋综合管廊的地震损伤,利用ABAQUS建立土-结构整体有限元模型,以综合管廊层间位移角最大值为损伤指标,基于IDA方法进行结构地震易损性分析,重点考察近断层地震动强度指标和场地土特性对综合管廊抗震性能的影响。结果表明:近断层地震动加速度型指标的离散性最小,建议选取加速度型指标PGA、Sa作为地震动强度指标;以有限元计算数据为样本,采用BP神经网络可高效预测综合管廊结构的地震损伤,PGA、Sa及土体剪切模量对综合管廊地震易损性分析的影响较大,随着土体剪切模量的增大,超越概率逐渐减小,同时,LS、CP状态的超越概率变化范围要明显大于OP、IO状态;考虑PGA和Sa双参数更能准确反映不同地震动参数对结构损伤的影响,而仅考虑PGA或Sa单参数有可能高估结构的损伤程度。因此,对综合管廊等浅埋地下结构进行地震易损性分析时,建议综合考虑PGA和Sa的影响。

关键词：综合管廊近断层地震动地震易损性强度指标 BP神经网络

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Participant Heterogeneity of Systemic Scleroderma Interventional Trials Worldwide

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International Journal of Dermatology and Venereology 2024年第2期7卷 99-107页

作者： Li-Qing Shi Shi-Hang Zhou Ping-Lang Ruan bo Zhang Yue Xin cheng Zhao Xu Yao Jing-Ru Tian Qian-Jin Lu Hospital for Skin Diseases(Institute of Dermatology) Chinese Academy of Medical Sciences and Peking Union Medical CollegeNanjingJiangsu 210042China Key Laboratory of Basic and Translational Research on Immune-Mediated Skin Diseases Chinese Academy of Medical SciencesNanjingJiangsu 210042China Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs NanjingJiangsu 210042China Department of Dermatology Hunan Key Laboratory of Medical Epigenomicsthe Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

Objective:Heterogeneity of participants in clinical trials distorts intervention ***,factors associated with participant heterogeneity in randomized clinical trials(RCTs)focusing on systemic sclerosis(SSc)are not *** conducted this systematic review to establish normative standards for future research and help develop management ***:Three databases and 4 registries were searched to identify characteristics of SSc RCTs across different *** of bias was assessed by the Cochrane Collaboration’s tool and logistic regression was performed to calculate crude and adjusted odds ***:In total,261 trials met our inclusion *** quality of SSc RCTs worldwide was relatively poor,with no trend of improvement in recent years,and only 12.2%were ranked as having a low risk of *** with a low risk of bias as well as single-center,single-country,or open-label trials tended to have better participant adherence than trials with a high risk of bias and multiple-center,multiple-country,or double-blind ***,trial registration and primary outcome definition contributed to high *** income was also relevant;participant adherence in high-income countries,but not in upper-and lower-middle-income countries,was significantly altered by different ***:Overall,the risk of bias,national income,and trial design may lead to participant heterogeneity of SSc RCTs and ultimately confound the general clinical utility of the *** with a rigorous design and transparent conduction protocol are crucial for obtaining unbiased data that can serve as a reference and for maintaining the fundamental repeatability of SSc RCTs.

关键词： systemic sclerosis randomized clinical trials heterogeneity participant adherence national income risk of bias

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Development of 400-μW cryogen-free dilution refrigerators for quantum experiments

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Chinese Physics B 2024年第7期33卷 28-35页

作者：关翔樊洁边勇波程智刚姬忠庆 Institute of Physics Chinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100190China

We have successfully developed cryogen-free dilution refrigerators with medium cooling power that can be applied to quantum experiments. Breakthroughs have been made in some key technologies and components of heat switches and dilution units. Our prototype has been running continuously and stably for more than 100 hours below 10 m K, with a minimum temperature of 7.6 m K and a cooling power of 450 μW at 100 m K. At the same time, we have also made progress in the application of dilution refrigerators, such as quantum computing, low-temperature detector, and magnet integration. These indicators and test results indicate good prospects for application in physics, astronomy, and quantum information.

关键词： cryogen-free dilution refrigerator quantum computing low-temperature detector superconducting magnet

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当代西方技术民族主义的本质意涵与表现类型

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科学学研究 2024年第3期42卷 484-491页

作者：程志波中国矿业大学马克思主义学院江苏徐州221116

从民族、民族主义与技术民族主义的内在关系看,技术民族主义是民族主义思潮在科技活动中的渗透与体现,其本质特征是特定民族-国家为追求或维护本民族-国家的技术独立或领先地位,要求本民族-国家技术活动遵循民族-国家利益至上原则,强调... 详细信息

从民族、民族主义与技术民族主义的内在关系看,技术民族主义是民族主义思潮在科技活动中的渗透与体现,其本质特征是特定民族-国家为追求或维护本民族-国家的技术独立或领先地位,要求本民族-国家技术活动遵循民族-国家利益至上原则,强调“自我技术”与“他者技术”的区分,包含情感、理论与政策三个层面。以目的-手段作为参量,当代西方技术民族主义可分为垄断-激进技术民族主义、垄断-温和技术民族主义、自利-激进技术民族主义、自利-温和技术民族主义四种基本类型,它们衍生于不同理论、现实与制度基础之上。

关键词：技术民族主义民族-国家目的-手段表现类型

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MAPK9 as a therapeutic target:unveiling ferroptosis in localized prostate cancer progression

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BIOCELL 2024年第5期48卷 771-792页

作者： cheng-GONG LUO JIAO ZHANG YUN-ZHAO AN XUAN LIU SHUAI-JIE LI WEI ZHANG KAI LI XU ZHAO DONG-bo YUAN LING-YUE AN WEI CHEN YE TIAN BIN XU Department of Urology Guizhou Provincial People’s HospitalGuiyangChina Department of Urology First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina

Background:Ferroptosis,a lipid peroxidation-mediated programmed cell death,is closely linked to tumor development,including prostate cancer(PCa).Despite established connections between ferroptosis and PCa,a comprehensive investigation is essential for understanding its impact on patient ***:A risk model incorporating four ferroptosis-related genes was developed and *** risk scores correlated with an increased likelihood of biochemical recurrence(BCR),diminished immune infiltration,and adverse clinicopathological *** corroborate these results,we performed validation analyses utilizing datasets from both the Cancer Genome Atlas Cohort(TCGA)and the Gene Expression Synthesis Cohort(GEO).Moreover,we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays,as well as animal studies conducted in ***,we conducted further experiments involving ferroptosis-related analysis to validate its association with ***:The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa ***-activated protein kinase 9(MAPK9)emerged as a crucial gene within the *** vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and ***:The findings provide a novel perspective for advancing ferroptosis exploration in PCa,bridging basic research and clinical applications.

关键词： Ferroptosis Biochemical recurrence Prostate cancer TCGA GEO MAPK9

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Phospholipase A2 enzymes PLA2G2A and PLA2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 289-306页

作者： Chen Qiu Yu-Kai Xiang Xuan-bo Da Hong-Lei Zhang Xiang-Yu Kong Nian-Zong Hou cheng Zhang Fu-Zhou Tian Yu-Long Yang Center of Gallbladder Disease Shanghai East HospitalInstitute of Gallstone DiseaseSchool of MedicineTongji UniversityShanghai 200092China General Surgery Center Chengdu Military General HospitalChengdu 610083Sichuan ProvinceChina

BACKGROUND Phospholipase A2(PLA2)enzymes are pivotal in various biological processes,such as lipid mediator production,membrane remodeling,bioenergetics,and maintaining the body surface ***,these enzymes play a significant role in the development of diverse *** To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma(CCA).METHODS We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression *** study identified differentially expressed genes between tumor tissues and adjacent normal tissues,with a focus on PLA2G2A and *** Set Enrichment Analysis was utilized to pinpoint associated ***,relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted,and their correlation with the prognosis of CCA was *** PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA,manifesting significant variations in expression levels in urine and serum between CCA patients and healthy *** expression of PLA2G2A was correlated with poorer overall survival in CCA ***,the study delineated pathways and miRNAs associated with these *** Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for *** increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA,and their expression levels are indicative of prognosis,underscoring their potential utility in clinical settings.

关键词： PLA2G2A PLA2G12B Diagnostic Prognostic biomarkers cholangiocarcinoma

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