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Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4087-4101页

作者： Zaigang Zhou Wenjuan Luo Chunjuan Zheng Haoxiang Wang Rui Hu Hui Deng Jianliang Shen National Engineering Research center of Ophthalmology and Optometry Eye HospitalWenzhou Medical UniversityWenzhou 325027China School&Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325027China Zhejiang Engineering Research center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001China Department of the second Affiliated Hospital of Wenzhou Medical University Wenzhou 325000China

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to theimpaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile,acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1(PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps,we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer withmitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF-bdual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase(AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugatingmitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembledwith albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticleseffectively decreased the expression of collagen in vitro, which then led to the enhanced accumulation ofPTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-b in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cellinfiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy toinhibit PTX@Alb-resistant tumors, further supporting its better clinical application。

关键词： Chemo-immunotherapy Collagen Transforming growth factor-b Mitochondrial metabolism Programmed cell deathligand 1 Drug accumulation Albumin-bound paclitaxel Immune-resistance microenvironment

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A Transformer-Based Ensemble Framework for the Prediction of Protein-Protein Interaction Sites

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Research 2024年第2期2023卷 703-718页

作者： Minjie Mou Ziqi Pan Zhimeng Zhou Lingyan Zheng Hanyu Zhang Shuiyang Shi Fengcheng Li Xiuna Sun Feng Zhu College of Pharmaceutical Sciences The Second Affliated HospitalZhejiang University School of MedicineNational Key Laboratory of Advanced Drug Delivery and Release SystemsZhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University Alibaba-Zhejiang University Joint Research Center of Future Digital HealthcareHangzhou 330110China

The identification of protein-protein interaction (PPI) sites is essential in the research of protein function and the discovery of new drugs. So far, a variety of computational tools based on machine learning have been developed to accelerate the identification of PPI sites. However, existing methods suffer from the low predictive accuracy or the limited scope of application. Specifically, some methods learned only global or local sequential features, leading to low predictive accuracy, while others achieved improved performance by extracting residue interactions from structures but were limited in their application scope for the serious dependence on precise structure information. There is an urgent need to develop a method that integrates comprehensive information to realize proteome-wide accurate profiling of PPI sites. Herein, a novel ensemble framework for PPI sites prediction, EnsemPPIS, was therefore proposed based on transformer and gated convolutional networks. EnsemPPIS can effectively capture not only global and local patterns but also residue interactions. Specifically, EnsemPPIS was unique in (a) extracting residue interactions from protein sequences with transformer and (b) further integrating global and local sequential features with the ensemble learning strategy. Compared with various existing methods, EnsemPPIS exhibited either superior performance or broader applicability on multiple PPI sites prediction tasks. Moreover, pattern analysis based on the interpretability of EnsemPPIS demonstrated that EnsemPPIS was fully capable of learning residue interactions within the local structure of PPI sites using only sequence information. The web server of EnsemPPIS is freely available at http://***/ensemppis.

关键词： residue extracting ensemble

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Review of the application of Rotational Motions in Seismology

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Earthquake Research in China 2018年第4期32卷 456-469页

作者： Zhang Pei Liu Wenyi Yuan Yi Li Jun the second monitoring and application center China Earthquake Administration

Rotational seismology is an emerging field for studying all aspects of rotational ground motions induced by earthquakes,explosions,and ambient vibrations. It is of interest to a wide range of geophysical disciplines,including strong-motion seismology,earthquake engineering,earthquake physics,seismic instrumentation,as well as to the complete description of particle motions( translational motion,rotational motion and deformation).This article mainly summarizes the application of rotational motions to seismology. Based on the collocated measurements of translational motion and rotational motion, the theoretical formulas of calculating the teleseismic Rayleigh wave and the Love wave phase velocity are derived. Taking the Siberian earthquake as an example,the phase velocity structure near the station is calculated. As a ring laser that's sensitive only to SH-type motion,one of the expectations of the ring laser measurements is to help seismologists separate P and S waves in the wave field. It also helps distinguish Love and Rayleigh wave energy in the ocean-generated noise field,as well as determine the back azimuth of oceanic noise sources. The long-period toroidal modes of free oscillation, one of the most challenging observations in seismology,are then observed with a ring laser. Finally,the importance and practicability of multi-parameter inversions including rotational observations are expounded. At the end of this paper,we present the existing problems in rotational seismology research and its broad application prospects.

关键词： Rotational motions Surface wave Tomography Ring laser technology Free oscillation Multi-parameter inversion

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The NE Directed Seismicity Belt in Tibet after the M_S8.1 Nepal Earthquake and Its Predictive Significance

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Earthquake Research in China 2018年第1期32卷 119-129页

作者： Wang Shuangxu Zhu Liangyu Xu Jing Ji Lingyun Jiang Fengyun the second monitoring and application center China Earthquake Administration

After the 2015 M_S8. 1 Nepal earthquake,a strong and moderate seismicity belt has formed in Tibet gradually spreading along the northeast direction. In this paper,we attempt to summarize the features and investigate the primary mechanism of this behavior of seismic activity,using a 2-D finite element numerical model with tectonic dynamic settings and GPS horizontal displacements as the constraints. In addition,compared with the NEtrending seismicity belt triggered by the 1996 Xiatongmoin earthquake,we discuss the future earthquake hazard in and around Tibet. Our results show that: the NE-directed seismicity belt is the response of enhanced loading on the anisotropic Qinghai-Tibetan plateau from the Indian plate and earthquake thrusting. Also,this possibly implies that a forthcoming strong earthquake may fill in the gaps in the NE-directed seismicity belt or enhance the seismic hazard in the eastern( the north-south seismic zone) and western( Tianshan tectonic region) parts near the NE-directed belt.

关键词： The 2015 M S8.1 Nepal earthquake Qinghai-Tibetan plateau NE-directed seismicity belt predictive significance

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Study of main body element of crustal strain and its relationship with moderate-strong earthquakes

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Acta Seismologica Sinica(English Edition) 2006年第1期19卷 54-61页

作者：陈兵张晓亮王庆良刘文义王敏薄万举 second Crustal monitoring and application center China Earthquake Administration Xi'an 710054 China Institute of Earthquake Science China Earthquake Administration Beijing 100036 China First Crustal monitoring and application center China Earthquake Administration Tianjin 300180 China

In this paper, progress in strain study of blocks and faults by GPS data are discussed, and the concept that active structures between blocks are the main body of crustal strain is clarified. By energy transfer principle of elastic mechanics, the relation between strain around faults and tectonic force on fault surfaces is set up and main body element model of crustal strain is constructed. Finally, the relation between mechanical evolution of model and seismogenic process of Kunlun earthquake （Ms=8.1） is discussed by continuous GPS data of datum stations. The result suggests that the relatively relaxed change under background of strong compressing and shearing may help to trigger moderate-strong earthquakes.

关键词： main body element of crustal strain tectonic force on fault surface energy transfer GPS benchmark site postseismic relative relaxation

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AAV for Gene Therapy in Ocular Diseases:Progress and Prospects

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Research 2024年第3期2023卷 651-670页

作者： Xiaoyu He Yidian Fu Liang Ma Yizheng Yao Shengfang Ge Zhi Yang Xianqun Fan Department of Ophthalmology Ninth People’s HospitalShanghai JiaoTong University School of MedicineShanghaiChina Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology ShanghaiChina Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow UniversityClinical Research Center of Neurological DiseaseThe Second Affiliated Hospital of Soochow UniversitySuzhouChina

Owing to the promising therapeutic effect and one-time treatment advantage, gene therapy may completely change the management of eye diseases, especially retinal diseases. Adeno-associated virus (AAV) is considered one of the most promising viral gene delivery tools because it can infect various types of tissues and is considered as a relatively safe gene delivery vector. The eye is one of the most popular organs for gene therapy, since its limited volume is suitable for small doses of AAV stably transduction. Recently, an increasing number of clinical trials of AAV-mediated gene therapy are underway. This review summarizes the biological functions of AAV and its application in the treatment of various ocular diseases, as well as the characteristics of different AAV delivery routes in clinical applications. Here, the latest research progresses in AAV-mediated gene editing and silencing strategies to modify that the genetic ocular diseases are systematically outlined, especially by base editing and prime editing. We discuss the progress of AAV in ocular optogenetic therapy. We also summarize the application of AAV-mediated gene therapy in animal models and the difficulties in its clinical transformation.

关键词： AAV organs treatment

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Advances in metal-organic framework-derived single-atom catalysts for biomedicine

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Nano Materials Science 2024年第4期6卷 396-412页

作者： Li Qiu Yingxi Lin Jun Song Chen Hong Luo Rui Wu Department of Ultrasound West China Second University Hospital Sichuan University Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education Sichuan University School of Materials and Energy University of Electronic Science and Technology of China Interdisciplinary Materials Research center Institute for Advanced Study Chengdu University

As a alternative for natural enzymes, nanozymes has shown enzyme-like activity and selectivity in the field of various kinds of biomedical application, which has attracted considerable research interest. Recently, single-atom catalysts(SACs) have been extensively studied due to their similar active centers, coordination environment and better stability to natural enzymes. Metal-organic frameworks(MOFs) have been demonstrated as highly promising precursors for the synthesis of various types of SACs. MOF-derived SACs can not only significantly enhance the catalytic activity, but also improve the selectivity of nanozymes due to tunable coordination environment and structure, thereby receiving widespread attention in biomedicine. This review provided an overview of the preparation strategies for MOF-derived SACs, and then detailed the latest research progress of the SACs in the biomedical field for cancer, antibacterial, antioxidation and biosensors. Finally, the challenges and potential future opportunities of MOF-derived SACs in biomedical applications are proposed.

关键词： Biomedicine MOF-Derived SAC nanozymes Catalytic mechanisms

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Retrieval of Antarctic sea ice freeboard and thickness from HY-2B satellite altimeter data

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Acta Oceanologica Sinica 2024年第3期43卷 87-101页

作者： Yizhuo Chen Xiaoping Pang Qing Ji Zhongnan Yan Zeyu Liang Chenlei Zhang Chinese Antarctic center of Surveying and Mapping Wuhan UniversityWuhan 430079China Key Laboratory of Polar Surveying and Mapping Science Ministry of Natural ResourcesWuhan 430079China Key Laboratory of Polar Environment monitoring and Public Governance Ministry of EducationWuhan 430079China 4 School of Geography and Tourism Anhui Normal UniversityWuhu 241002China

Antarctic sea ice is an important part of the Earth’s atmospheric system,and satellite remote sensing is an important technology for observing Antarctic sea *** Chinese Haiyang-2B(HY-2B)satellite altimeter data could be used to estimate sea ice freeboard and provide alternative Antarctic sea ice thickness information with a high precision and long time series,as other radar altimetry satellites can,needs further *** paper proposed an algorithm to discriminate leads and then retrieve sea ice freeboard and thickness from HY-2B radar altimeter *** first collected the Moderate-resolution Imaging Spectroradiometer ice surface temperature(IST)product from the National Aeronautics and Space Administration to extract leads from the Antarctic waters and verified their accuracy through Sentinel-1 Synthetic Aperture Radar ***,a surface classification decision tree was generated for HY-2B satellite altimeter measurements of the Antarctic waters to extract leads and calculate local sea surface *** then estimated the Antarctic sea ice freeboard and thickness based on local sea surface heights and the static equilibrium ***,the retrieved HY-2B Antarctic sea ice thickness was compared with the CryoSat-2 sea ice thickness and the Antarctic Sea Ice Processes and Climate(ASPeCt)ship-based observed sea ice *** results indicate that our classification decision tree constructed for HY-2B satellite altimeter measurements was reasonable,and the root mean square error of the obtained sea ice thickness compared to the ship measurements was 0.62 *** proposed sea ice thickness algorithm for the HY-2B radar satellite fills a gap in this application domain for the HY-series satellites and can be a complement to existing Antarctic sea ice thickness products;this algorithm could provide long-time-series and large-scale sea ice thickness data that contribute to research on global climate change.

关键词： HY-2B satellite altimeter classification decision tree sea ice freeboard and thickness Antarctic waters

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Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and *** This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow *** In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<*** Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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Recent progress in the biomedical application of PEDOT:PSS hydrogels

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Chinese Chemical Letters 2024年第10期35卷 39-53页

作者： Binhan Zhao Zheng Li Lan Zheng Zhichao Ye Yuyang Yuan Shanshan Zhang Bo Liang Tianyu Li School of Medicine Zhejiang University Biosensor National Special Laboratory College of Biomedical Engineering and Instrument Science Zhejiang University National Engineering Research center of Innovation and application of Minimally Invasive Instruments Sir Run Run Shaw Hospital School of MedicineZhejiang University Department of Translational Medicine & Clinical Research Sir Run Run Shaw Hospital School of Medicine Zhejiang University

Bioelectronics have gained substantial research attention owing to their potential applications in health monitoring and diagnose, and greatly promoted the development of biomedicine. Recently, poly(3,4-ethylenedioxythiophene):polystyrene sulfonate(PEDOT:PSS) hydrogels have arose as a promising candidate for the next-generation bioelectronic interface due to its high-conductivity, versatility, flexibility and biocompatibility. In this review, we highlight the recent advances of PEDOT:PSS hydrogels, including the gelation methods and modification strategies, and summarize their wide applications in different type of sensors and tissue engineering in detail. We expect that this work will provide valuable information regarding the functionalizations and applications of PEDOT:PSS hydrogels.

关键词： Biomedical application Conducting polymer Conjugated polymer Gelation methods PEDOT:PSS hydrogels

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