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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin medical Research center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational medical center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

Variable frequency deep brain stimulation of subthalamic nucleus to improve freezing of gait in Parkinson's disease

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National Science Review 2024年第6期11卷 102-104页

作者： Fumin Jia Aparna Wagle Shukla Wei Hu Yu Ma Jianguo Zhang Leonardo Almeida Chris Kao Yi Guo Shizhong Zhang Yingqun Tao Zhipei Ling Xin Xu Zhiquan Yang Fan-gang Meng Xinhua Wan Hesheng Liu Peter E.Konard Luming Li National Engineering Laboratory for Neuromodulation Tsinghua University university of Florida center for Movement Disorders and Neurorestoration Tsinghua university Yuquan hospital Beijing Tiantan hospital Capital Medical University School of Medicine Vanderbilt University Peking Union medical College hospital ZhuJiang hospital of Southern medical university The General hospital of Shenyang Military Chinese PLA General hospital Xiangya hospital Central South university Beijing Neurosurgical Institute Capital Medical University Athinoula A. Martinos center for Biomedical Imaging Harvard Medical School Precision Medicine & Healthcare Research center Tsinghua-Berkeley Shenzhen Institute Man-Machine-Environment Engineering Institute School of Aerospace EngineeringTsinghua University center of Epilepsy Beijing Institute for Brain Disorders

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a welle-stablished therapy for patients with Parkinson’s disease (PD) presenting with medication refractory tremors, motor fluctuations and dyskinesias induced by dopaminergic medications [1]. However,traditional high-frequency stimulation(HFS) does not effectively control axial symptoms such as gait dysfunction,postural instability and freezing of gait(FOG)[2,3].

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Reinfection and Risk Factors of SARS-CoV-2 during an Omicron Wave 2022 in Shanghai

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Biomedical and Environmental Sciences 2024年第2期37卷 204-209页

作者： WANG Pei Qin WANG Xiao Hang WANG Jian SHI Zhi Wen CHU Dong Mei WANG Zhi Fei ZHANG Mu Bai LIU Wei ZHOU Zi Jie XIE Wei Fen Department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghai 200003China Health examination center Changzheng HospitalNaval Medical UniversityShanghai 200003China

Multiple waves of coronavirus disease 2019(COVID-19) outbreaks have affected numerous countries worldwide. The first case of SARS-CoV-2 reinfection was reported in Hong Kong in August 2020^([1]), leading to increased interest in the effectiveness of natural immunity acquired from primary infection. While data reports vary across countries, all findings indicate that prior SARS-CoV-2 infection provides substantial protection against reinfection^([2]). However, natural immunity from infection with previous non-Omicron or early Omicron sub-lineages offers lower levels of protection against Omicron reinfection, with rates below 60%^([3]) and approximately 75%[4], respectively.

关键词： immunity infection Omi

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Real-Time 3D Ultrasound Imaging System Based on a Hybrid Reconstruction Algorithm

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Chinese Journal of Electronics 2024年第1期33卷 245-255页

作者： Yifei LYU Yu SHEN Mingbo ZHANG Junchen WANG School of Mechanical Engineering and Automation Beihang University The First medical center General Hospital of Chinese PLA

As a safe and convenient imaging technology in clinical routine diagnosis, ultrasound imaging can provide real-time 2D images of internal tissues and organs. To realize real-time 3D image reconstruction, pixel nearest neighbor interpolation(PNN) reconstruction algorithm and Bezier interpolation algorithm are combined into a hybrid reconstruction algorithm. On this basis, a real-time interactive 3D ultrasound imaging system is *** temporal calibration and spatial calibration, the six degrees of freedom poses of 2D ultrasound images can be accurately collected. The 3D volume reconstructed by the proposed 3D reconstruction algorithm is visualized by volume rendering. A multi-thread software system allows parallel operation of data acquisition, 3D reconstruction,volume visualization and other functions. 3D imaging experiments on a 3D printing femur model, a neck phantom and the neck of human volunteers were performed for systematic evaluation. When the reconstruction voxel size was set to be(0.53 mm3, 1.03 mm3, 1.53 mm3), the reconstruction errors of the femur and trachea model were respectively(0.23 mm, 0.31 mm, 0.56 mm) and(0.62 mm, 0.88 mm, 1.41 mm). Clinical feasibility was demonstrated by application of the 3D ultrasound imaging on the neck of human volunteers.

关键词： Interpolation Three-dimensional displays Ultrasonic imaging Imaging Data visualization Reconstruction algorithms Real-time systems

Paclitaxel-induced Immune Dysfunction and Activation of Transcription Factor AP-1 Facilitate Hepatitis B Virus Replication

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Journal of Clinical and Translational Hepatology 2024年第5期12卷 457-468页

作者： Shi Chen Benhua Li Wei Luo Adeel ur Rehman Miao He Qian Yang Shunyao Wang Jinjun Guo Ling Chen Xiaosong Li Clinical Molecular Medicine Testing center The First Affiliated HospitalChongqing Medical UniversityChongqingChina Affiliated Traditional Chinese Medicine hospital of Southwest medical university LuzhouSichuanChina Laboratory Animal center of Chongqing medical university ChongqingChina Bishan hospital of Chongqing Bishan Hospital of Chongqing Medical UniversityChongqingChina The center of Experimental Teaching Management Chongqing Medical UniversityChongqingChina

Background and Aims:Hepatitis B virus(HBV)reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug ***(PTX)treatment has been identified as a potential trigger for HBV *** study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo,which may inform new strategies for HBV antiviral ***:The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay,dual-luciferase reporter assay,quantitative real-time PCR,chromatin immunoprecipitation,and immunohistochemical *** sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic ***:PTX enhanced the levels of HBV 3.5-kb mRNA,HBV DNA,HBeAg,and HBsAg both in vitro and in *** also promoted the activity of the HBV core promoter and transcription factor *** of AP-1 gene expression markedly suppressed PTX-induced HBV *** sequencing revealed that PTX activated the immune-related signaling networks such as IL-17,NF-􀇉B,and MAPK signaling pathways,with the pivotal common key molecule being *** 16S rRNA sequencing revealed that PTX induced dysbiosis of gut ***:PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor *** findings propose a novel molecular mechanism,underscoring the critical role of AP-1 in PTX-induced HBV reactivation.

关键词： Paclitaxel HBV reactivation Transcription factor AP-1 Immune system Gut microbiota

Electrospun PCL/gelatin/arbutin nanofiber membranes as potent reactive oxygen species scavengers to accelerate cutaneous wound healing

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Regenerative Biomaterials 2024年第3期3卷 43-55页

作者： Mindong Du Shuhan Liu Nihan Lan Ruiming Liang Shengde Liang Maoqiang Lan Disen Feng Li Zheng Qingjun Wei Ke Ma Department of Orthopaedics Trauma and Hand Surgery The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530521China Guangxi Engineering center in Biomedical Materials for Tissue and Organ Regeneration The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medicar UniversityNanning530021China Guangxi Collaborative Innovation center for Biomedicine The First Affliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China Department of Plastic&Cosmetic Surgery.The First Affliated hospital of Guangxi medical university Guangxi Medical UniversityNanning 530021China Pharmaceutical College Guangxi Medical UniversityNanning530021China

The presence of excessive reactive oxygen species(Ros)at a skin wound site is an important factor affecting wound *** scavenging,which regulates the ROS microenvironment,is essential for wound *** this study,we used novel electrospun PCL/gelatin/arbutin(PCL/G/A)nanofibrous membranes as wound dressings,with PCL/gelatin(PCL/G)as the backbone,and plantderived arbutin(hydroquinone-β-D-glucopyranoside,ARB)as an effective antioxidant that scavenges ROos and inhibits bacterial infection in *** loading of ARB increased the mechanical strength of the nanofibres,with a water vapour transmission rate of more than 2500g/(m^(2)×24h),and the water contact angle decreased,indicating that hydrophilicity and air permeability were significantly *** release and degradation experiments showed that the nanofibre membrane controlled the drug release and exhibited favourable *** experiments showed that the PCL/G/A nanofibre membranes were biocompatible,and DPPH and ABTS+radical scavenging experiments indicated that PCL/G/A could effectively scavenge ROS to reflect the antioxidant *** addition,haemostasis experiments showed that PCL/G/A had good haemostatic effects in vitro and in *** vivo animal wound closure and histological staining experiments demonstrated that PCL/G/A increased collagen deposition and remodelled epithelial tissue regeneration while showing good in vivo biocompatibility and *** conclusion,we successfully prepared a multifunctional wound dressing,PCL/G/A,for skin wound healing and investigated its potential role in wound healing,which is beneficial for the clinical translational application of phytomedicines.

关键词： arbutin nanofiber membranes wound dressing reactive oxygen species

Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin

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Science China(Life Sciences) 2024年第6期67卷 1226-1241页

作者： Zhengyang Guo Jiaqi Huang Xiao Huo Chen Huang Xiaotong Yu Yan Sun Yanfang Li Tianhui He Hongyan Guo Jianling Yang Lixiang Xue Cancer center of Peking university Third hospital Beijing 100191China center of Basic medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Peking university Third hospital Cancer center Department of Radiation OncologyPeking University Third HospitalBeijing 100191China Department of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China

Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed *** ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism *** a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian ***,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related *** 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the *** data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian *** of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian ***,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian *** findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.

关键词： ovarian cancer polyunsaturated fatty acids prognostic risk model LTA4H tumor immunity CCL5

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Single-cell RNA sequencing analysis of the retina under acute high intraocular pressure

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Neural Regeneration Research 2024年第11期19卷 2522-2531页

作者： Shaojun Wang Siti Tong Xin Jin Na Li Pingxiu Dang Yang Sui Ying Liu Dajiang Wang Division of Ophthalmology The Third Medical Center of PLA General HospitalBeijingChina Department of Ophthalmology Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

High intraocular pressure causes retinal ganglion cell injury in primary and secondary glaucoma diseases,yet the molecular landscape characteristics of retinal cells under high intraocular pressure remain *** models of acute hypertension ocular pressure were established by injection of cross-linked hyaluronic acid hydrogel(Healaflow■).Single-cell RNA sequencing was then used to describe the cellular composition and molecular profile of the retina following high intraocular *** results identified a total of 12 cell types,namely retinal pigment epithelial cells,rod-photoreceptor cells,bipolar cells,Müller cells,microglia,cone-photoreceptor cells,retinal ganglion cells,endothelial cells,retinal progenitor cells,oligodendrocytes,pericytes,and *** single-cell RNA sequencing analysis of the retina under acute high intraocular pressure revealed obvious changes in the proportions of various retinal cells,with ganglion cells decreased by 23%.Hematoxylin and eosin staining and TUNEL staining confirmed the damage to retinal ganglion cells under high intraocular *** extracted data from retinal ganglion cells and analyzed the retinal ganglion cell cluster with the most distinct *** found upregulation of the B3gat2 gene,which is associated with neuronal migration and adhesion,and downregulation of the Tsc22d gene,which participates in inhibition of *** study is the first to reveal molecular changes and intercellular interactions in the retina under high intraocular *** data contribute to understanding of the molecular mechanism of retinal injury induced by high intraocular pressure and will benefit the development of novel therapies.

关键词： apoptosis axon degeneration high intraocular pressure microglia ocular hypertension photoreceptor cells retina retinal degeneration retinal ganglion cells single-cell RNA sequencing

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Minimizing the ratio of ionizable lipid in lipid nanoparticles for in vivo base editing

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National Science Review 2024年第6期11卷 285-293页

作者： Qiubing Chen Xuebin Wang Yizhou Zhang Ming Tian Junyi Duan Ying Zhang Hao Yin Departments of Urology and Laboratory Medicine Frontier Science Center for Immunology and Metabolism Medical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan University State Key Laboratory of Virology Tai Kang Center for Life and Medical Sciences Tai Kang Medical SchoolWuhan University Department of Rheumatology and Immunology Zhongnan Hospital of Wuhan UniversityWuhan University Wuhan Research center for Infectious Diseases and Cancer Chinese Academy of Medical Sciences RNA Institute Wuhan University

Lipid nanoparticles(LNPs) have gained clinical approval as carriers for both siRNA and mRNA. Among the crucial components of LNPs, ionizable lipids play a pivotal role in determining the efficiency of RNA delivery. In this study, we synthesized a series of ionizable lipids, denoted as HTO, with a higher count of hydroxyl groups compared to SM-102. Remarkably, LNPs based on HTO12 lipid demonstrated comparable mRNA delivery efficiency and biosafety to those based on SM-102. However, the former reduced the ratio of ionizable lipid/total lipids to mRNA in LNPs by 2.5 times compared to SM-102. The HTO12 LNP efficiently encapsulated adenine base editor mRNA and sgRNA targeting Pcsk9, leading to substantial gene editing within the liver of mice and effective reduction of the target protein. Our study underscores that ionizable lipids with multiple hydroxyl groups may facilitate an improved lipid-to-mRNA ratio to minimize the dosage of ionizable lipids for in vivo delivery.

关键词： ionizable lipid lipid nanoparticle mRNA delivery base editor delivery Pcsk9