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A Dynamic Covalent Bonding-based Nanoplatform for Intracellular Co-Delivery of Protein Drugs and Chemotherapeutics with Enhanced Anti-Cancer Effect

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Chinese Journal of Polymer Science 2024年第5期42卷 559-569,I0005页

作者： Sai-Nan Liu Jia-hui Meng Li-Yun Cui Hua Chen Lin-Qi Shi ru-Jiang Ma Key Laboratory of Functional Polymer Materials of Ministry of Education Institute of Polymer ChemistryTianjin Key Laboratory of Functional Polymer MaterialsState Key Laboratory of Medicinal Chemical BiologyFrontiers Science Center for New Organic MatterCollege of ChemistryNankai UniversityTianjin300071China Haihe Laboratory of Sustainable Chemical Transformations Tianjin300192China

Efficient intracellular delivery of protein drugs is critical for protein *** combination of protein drugs with chemotherapeutics represents a promising strategy in enhancing anti-cancer ***,co-delivery systems for efficient delivery of these two kinds of drugs are still lacking because of their different ***,we show a well-designed delivery system based on dynamic covalent bond for efficient intracellular co-delivery of ribonuclease A(RNase A)and doxorubicin(DOX).Two polymers,PEG-b-P(Asp-co-AspDA)and PAE-b-P(Asp-co-AspPBA),and two 2-acetylphenylboronic acid(2-APBA)-functionalized drugs,2-APBA-RNase A and 2-APBA-DOX,self-assemble into mixed-shell nanoparticles(RNase A/DOX@MNPs)via dynamic phenylboronic acid(PBA)-catechol bond between PBA and dopamine(DA)*** PBA-catechol bond endows the nanoparticles with high stability and excellent stimulus-responsive drug release *** the slight acidic environment at tumor tissue,RNase A/DOX@MNPs are positively charged,promoting their *** cellular uptake into endosome,further protonation of PAE chains leads to the rupture of endosomes because of the proton sponge effect and the cleavage of PBA-catechol bond promotes the release of two *** cytoplasm,the high level of GSH removed the modification of 2-APBA on *** restored RNase A and DOX show a synergistic and enhanced antic-cancer *** system may be a promising platform for intracellular co-delivery of protein drugs and chemotherapeutics.

关键词： Drug co-delivery Combination therapy Dynamic covalent bond

Interfacial charge redistribution to promote the catalytic activity of Vs-CoP-CoS_(2)/C n-n heterojunction for oxygen evolution

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Chinese Chemical Letters 2024年第2期35卷 611-616页

作者： Jiawen Sun hui Xue Jing Sun Niankun Guo tianshan Song Yi-ru Hao Qin Wang College of Chemistry and Chemical Engineering Inner Mongolia UniversityHohhot 010021China

Modulating surface charge redistribution based on interface and defect engineering has been considered as a resultful means to boost electrocatalytic ***,the mechanism of synergistic regulation of heterojunction and vacancy defects remains ***,a Vs-CoP-CoS_(2)/C n-n heterojunction with sulfur vacancies is successfully constructed,which manifests superior electrocatalytic activity for oxygen evolution,as demonstrated by a low overpotential of 170 mV to reach 10 mA/cm^(2).The experimental results and density functional theory calculations testify that the outstanding OER performance of Vs-CoP-CoS_(2)/C heterojunction is owed to the synergistic effect of sulfur vacancies and built-in electric field at n-n heterogeneous interface,which accelerates the electron transfer,induces the charge redistribution,and regulates the adsorption energy of active intermediates during the *** study affords a promising means to regulate the electrocatalytic performance by the construction of heterogeneous interfaces and defects,and in-depth explores the synergistic mechanisms of n-n heterojunction and vacancies.

关键词： Charge redistribution n-n Heterojunction Built-in electric field Sulfur vacancy Oxygen evolution reaction

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

SIRT1 inhibits apoptosis of human lens epithelial cells through suppressing endoplasmic reticulum stress in vitro and in vivo

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1205-1216页

作者： hui Cui Di Sun Sheng Meng tian-Ju Ma Zi Ye Zhao-hui Li Medical School of Chinese PLA Beijing 100089China Senior Department of Ophthalmology the Third Medical Center of PLA General HospitalBeijing 100853China

AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing endoplasmic reticulum(ER)***:HLECs(SRA01/04)were treated with varying concentrations of tunicamycin(TM)for 24h,and the expression of SIRT1 and C/EBP homologous protein(CHOP)was assessed using real-time quantitative polymerase chain reaction(RT-PCR),Western blotting,and *** morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8(CCK-8)assay,*** the SRA01/04 cell apoptosis model,which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation,the expression levels of SIRT1,CHOP,glucose regulated protein 78(GRP78),and activating transcription factor 4(ATF4)were *** potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid(4-PBA;an ER stress inhibitor)was *** vivo,age-related cataract(ARC)rat models were induced by sodium selenite injection,and the protective role of SIRT1,activated by SRT1720 intraperitoneal injections,was evaluated through morphology observation,hematoxylin and eosin(H&E)staining,Western blotting,and ***:SIRT1 expression was downregulated in TMinduced SRA01/04 ***,in SRA01/04 cells,both cell apoptosis and CHOP expression increased with the rising doses of *** stress was stimulated by TM,as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis *** of SIRT1 by siRNA knockdown increased ER stress activation,whereas SRT1720 treatment had opposite results.4-PBA partly reverse the adverse effect of SIRT1 knockdown on *** vivo,SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat ***:SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in

关键词： silent information regulator factor 2-related enzyme 1 endoplasmic reticulum stress apoptosis human lens epithelial cells cataract

Implications of left atrial volume index in patients with three-vessel coronary disease:A 6.6-year follow-up cohort study

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Chinese Medical Journal 2024年第4期137卷 441-449页

作者： ru Liu Lei Song Ce Zhang Lin Jiang Jian tian Lianjun Xu Xinxing Feng Linyuan Wan Xueyan Zhao Ou Xu Chongjian Li runlin Gao rutai hui Wei Zhao Jinqing Yuan Department of Cardiology Fuwai HospitalChinese Academy of Medical SciencesBeijing 100037China Department of Respiratory and Pulmonary Vascular Disease Fuwai Yunnan Cardiovascular HospitalKunmingYunnan 650102China Department of Endocrinology Fuwai HospitalChinese Academy of Medical SciencesBeijing 100037China Department of Echocardiography Fuwai HospitalChinese Academy of Medical SciencesBeijing 100037China Information Center Fuwai HospitalChinese Academy of Medical SciencesBeijing 100037China

Background:Risk assessment and treatment stratification for three-vessel coronary disease(TVD)remain *** study aimed to investigate the prognostic value of left atrial volume index(LAVI)with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery(SYNTAX)score II,and its association with the long-term prognosis after three strategies(percutaneous coronary intervention[PCI],coronary artery bypass grafting[CABG],and medical therapy[MT])in patients with ***:This study was a post hoc analysis of a large,prospective cohort of patients with TVD in China,that aimed to determine the long-term outcomes after PCI,CABG,or optimal MT alone.A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital.A total of 7818 patients with available baseline LAVI data were included in the ***,procedural,and follow-up data were *** primary endpoint was major adverse cardiac and cerebrovascular events(MACCE),which was a composite of all-cause death,myocardial infarction(MI),and *** endpoints included all-cause death,cardiac death,MI,revascularization,and ***-term outcomes were evaluated among LAVI quartile ***:During a median follow-up of 6.6 years,a higher LAVI was strongly associated with increased risk of MACCE(Q3:hazard ratio[HR]1.20,95%confidence interval[CI]1.06-1.37,P=0.005;Q4:HR 1.85,95%CI 1.64-2.09,P<0.001),all-cause death(Q3:HR 1.41,95%CI 1.17-1.69,P<0.001;Q4:HR 2.54,95%CI 2.16-3.00,P<0.001),and cardiac death(Q3:HR 1.81,95%CI 1.39-2.37,P<0.001;Q4:HR 3.47,95%CI 2.71-4.43,P<0.001).Moreover,LAVI significantly improved discrimination and reclassification of the SYNTAX score ***,there was a significant interaction between LAVI quartiles and treatment strategies for *** was associated with lower risk of MACCE than MT alone,regardless of LAVI *** patients in the fourth quartile,PCI was associated with significantly incre

关键词： Three-vessel coronary disease Left atrial volume index Coronary artery bypass grafting Percutaneous coronary intervention Myocardial ischemia Prognosis

A survey on model-based reinforcement learning

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Science China(Information Sciences) 2024年第2期67卷 59-84页

作者： Fan-Ming LUO tian XU Hang LAI Xiong-hui CHEN Weinan ZHANG Yang YU National Key Laboratory for Novel Software Technology Nanjing University Polixir. ai Department of Computer Science and Engineering Shanghai Jiao Tong University

Reinforcement learning(RL) interacts with the environment to solve sequential decision-making problems via a trial-and-error approach. Errors are always undesirable in real-world applications, even though RL excels at playing complex video games that permit several trial-and-error attempts. To improve sample efficiency and thus reduce errors, model-based reinforcement learning(MBRL) is believed to be a promising direction, as it constructs environment models in which trial-and-errors can occur without incurring actual costs. In this survey, we investigate MBRL with a particular focus on the recent advancements in deep RL. There is a generalization error between the learned model of a non-tabular environment and the actual environment. Consequently, it is crucial to analyze the disparity between policy training in the environment model and that in the actual environment, guiding algorithm design for improved model learning, model utilization, and policy training. In addition, we discuss the recent developments of model-based techniques in other forms of RL, such as offline RL, goal-conditioned RL, multi-agent RL, and meta-RL. Furthermore,we discuss the applicability and benefits of MBRL for real-world tasks. Finally, this survey concludes with a discussion of the promising future development prospects for MBRL. We believe that MBRL has great unrealized potential and benefits in real-world applications, and we hope this survey will encourage additional research on MBRL.

关键词： reinforcement learning model-based reinforcement learning planning model learning model learning with reduced error model usage

Microseismic observations reveal that internal waves intensify seabed methane release

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Science China Earth Sciences 2024年第10期67卷 3186-3203页

作者： Zhaoyang tian Yonggang JIA Junjiang ZHU tian CHEN hui WANG Chunsheng JI Chengyu LIU Longyu LU Manchao HE Shandong Provincial Key Laboratory of Marine Environment and Geological Engineering Ocean University of China Frontiers Science Center for Deep Ocean Multispheres and Earth System Key Lab of Submarine Geosciences and Prospecting TechniquesMOE and College of Marine Geosciences Ocean University of China Guangzhou Marine Geological Survey China Geological Survey Shandong Earthquake Agency State Key Laboratory for Tunnel Engineering China University of Mining and Technology (Beijing)

Internal waves transport material and energy from the upper water column to the deep ocean, disturbing seabed sediments and resulting in phenomena such as seabed erosion and changes in topography. On the northern slope of the South China Sea and in many coastal margins worldwide, the zones with internal wave action closely overlap with areas where natural gas hydrates are present. However, due to significant differences in the spatial and temporal scales, understanding the influence of internal waves on methane releases from deep seabeds is challenging. In this study, in situ observations of seabed microseismicity and internal waves are conducted at water depths of 655 meters and 1450 meters in the Pearl River Canyon of the South China Sea. The microseismicity caused by internal waves and seabed methane releases is identified, and a method to establish the correlation between internal waves and seabed methane releases through the use of microseismic recordings is proposed, aiming to obtain direct observational evidence of internal waves intensifying seabed methane releases. The results show that internal waves and seabed methane releases generate significant microseismic signals, indicating the continuous influence of internal waves on the deep seabed of the northern slope of the South China Sea and revealing active methane release phenomena on the seabed. At both long and short time scales, internal waves increase the frequency of seabed methane releases by 4.2 times and 2.4 times, respectively, while also enhancing the intensity of these releases. These changes are influenced by the alterations in seabed flow velocity, pressure, and temperature that are induced by internal wave activities. This study emphasizes that microseismic signals are effective carriers of information for multiscale geological processes on seabeds and suggests that internal waves exacerbate marine geological hazards and contribute to global climate change by intensifying seabed methane relea

关键词： Internal waves Seabed methane release Microseismic observation Ocean bottom seismometer Northern slope of the South China Sea

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Quantum squeezing induced nonreciprocal phonon laser

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 20-30页

作者： tian-Xiang Lu Yan Wang Keyu Xia Xing Xiao Le-Man Kuang hui Jing College of Physics and Electronic Information Gannan Normal UniversityGanzhou 341000China Key Laboratory of Low-Dimensional Quantum Structures and Quantum Control of Ministry of Education Department of Physics and Synergetic Innovation Center for Quantum Effects and ApplicationsHunan Normal UniversityChangsha 410081China Academy for Quantum Science and Technology Zhengzhou University of Light IndustryZhengzhou 450002China College of Engineering and Applied Sciences National Laboratory of Solid State Microstructuresand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210023China

Phonon lasers or coherent amplifications of mechanical oscillations are powerful tools for fundamental studies on coherent acoustics and hold potential for diverse applications,ranging from ultrasensitive force sensing to phononic information ***,we propose the use of an optomechanical resonator coupled to a nonlinear optical resonator for directional phonon *** find that by pumping the nonlinear optical resonator,directional optical squeezing can occur along the pump *** a result,we can achieve the directional mechanical gain using directional optical squeezing,thereby leading to nonreciprocal phonon lasing with a well-tunable directional power *** work proposes a feasible way to build nonreciprocal phonon lasers with various nonlinear optical media,which are important for a wide range of applications,such as directional acoustic amplifiers,invisible sound sensing or imaging,and one-way phononic networks.

关键词： nonreciprocal phonon laser directional quantum squeezing optomechanics

Sora for foundation robots with parallel intelligence:three world models,three robotic systems

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Frontiers of Information Technology & Electronic Engineering 2024年第7期25卷 917-923页

作者： Lili FAN Chao GUO Yonglin tian hui ZHANG Jun ZHANG Fei-Yue WANG School of Information and Electronics Beijing Institute of TechnologyBeijing 100081China State Key Laboratory for Management and Control of Complex Systems Institute of AutomationChinese Academy of SciencesBeijing 100190China School of Computer and Information Technology Beijing Jiaotong UniversityBeijing 100044China School of Electrical Engineering Wuhan UniversityWuhan 430072China

This paper outlines the initial steps and basic framework for developing foundation/infrastructure robots/robotics based on foundation models and parallel intelligence,as well as the potential applications of new art... 详细信息

关键词： artificial foundation intelligence