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Tumor microenvironment reprogramming by nanomedicine to enhance the effect of tumor immunotherapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 1-37页

作者： Yu Huang Hui fan Huihui Ti School of Chinese Materia Medica Guangdong Pharmaceutical UniversityGuangzhou 510006China Guangdong Province Precise Medicine Big Date of Traditional Chinese Medicine Engineering Technology Research Center Guangdong Pharmaceutical UniversityGuangzhou 510006China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhou 510006China

With the rapid development of the fields of tumor biology and immunology, tumor immunotherapy has been used in clinical practice and has demonstrated significant therapeutic potential, particularly for treating tumors that do not respond to standard treatment options. Despite its advances, immunotherapy still has limitations, such as poor clinical response rates and differences in individual patient responses, largely because tumor tissues have strong immunosuppressive microenvironments. Many tumors have a tumor microenvironment (TME) that is characterized by hypoxia, low pH, and substantial numbers of immunosuppressive cells, and these are the main factors limiting the efficacy of antitumor immunotherapy. The TME is crucial to the occurrence, growth, and metastasis of tumors. Therefore, numerous studies have been devoted to improving the effects of immunotherapy by remodeling the TME. Effective regulation of the TME and reversal of immunosuppressive conditions are effective strategies for improving tumor immunotherapy. The use of multidrug combinations to improve the TME is an efficient way to enhance antitumor immune efficacy. However, the inability to effectively target drugs decreases therapeutic effects and causes toxic side effects. Nanodrug delivery carriers have the advantageous ability to enhance drug bioavailability and improve drug targeting. Importantly, they can also regulate the TME and deliver large or small therapeutic molecules to decrease the inhibitory effect of the TME on immune cells. Therefore, nanomedicine has great potential for reprogramming immunosuppressive microenvironments and represents a new immunotherapeutic strategy. Therefore, this article reviews strategies for improving the TME and summarizes research on synergistic nanomedicine approaches that enhance the efficacy of tumor immunotherapy.

关键词： Tumor immunotherapy Tumor micr oenvir onment Nanomedicine Tumor repr ogramming

SFC placement and dynamic resource allocation based on VNF performance-resource function and service requirement in cloud-edge environment

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Journal of Systems Engineering and Electronics 2024年第4期35卷 906-921页

作者： HAN Yingchao MENG Weixiao fan Wentao School of Electronics and Information Engineering Harbin Institute of TechnologyHarbin 150001China China Mobile(Suzhou)Software Technology Company Limited Suzhou 215000China

With the continuous development of network func-tions virtualization(NFV)and software-defined networking(SDN)technologies and the explosive growth of network traffic,the requirement for computing resources in the network has risen *** to the high cost of edge computing resources,coordinating the cloud and edge computing resources to improve the utilization efficiency of edge computing resources is still a considerable *** this paper,we focus on optimiz-ing the placement of network services in cloud-edge environ-ments to maximize the *** is first proved that,in cloud-edge environments,placing one service function chain(SFC)integrally in the cloud or at the edge can improve the utilization efficiency of edge *** a virtual network function(VNF)performance-resource(P-R)function is proposed to repre-sent the relationship between the VNF instance computing per-formance and the allocated computing *** select the SFCs that are most suitable to deploy at the edge,a VNF place-ment and resource allocation model is built to configure each VNF with its particular P-R ***,a heuristic recur-sive algorithm is designed called the recursive algorithm for max edge throughput(RMET)to solve the *** simula-tions on two scenarios,it is verified that RMET can improve the utilization efficiency of edge computing resources.

关键词： cloud-edge environment virtual network function(VNF)performance-resource(P-R)function edge resource allo-cation

Quantitative assessment of the supply,demand and flows of ecosystem services in the Yangtze River Basin,China

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Frontiers of Earth Science 2024年第2期18卷 422-445页

作者： Dongjie GUAN Xiaofeng fan Lilei ZHOU Kangwen ZHU School of Smart City Institute Chongqing Jiaotong UniversityChongqing 400074China

Ecosystem service flow is essential for transporting,transforming,and maintaining ecosystem services and connecting supply and *** study attempted to quantitatively assess the supply and demand flows of ecosystem services in the Yangtze River Basin in 2000,2010,and 2020;assess the evolution of the spatial patterns of ecosystem service flow at the provincial,watershed and urban agglomeration scales;and design a zoning standard for ecosystem service *** results showed as follows.1)Between 2000 and 2020,the Yangtze River had a progressive drop in its freshwater supply,water conservation service and carbon sequestration service *** decline rates for these services were measured at 10.90%,11.11%,and 5.17%,*** climate regulation service flow exhibited a pattern of initial fall followed by a subsequent increase,characterized by a decline rate of 35.53%.2)The lowest was the ecosystem service flow in the lower reaches of the Yangtze River and the Yangtze River Delta urban *** supply service flow and water conservation service flow were the highest in the upper reaches of the Yangtze River and the Chengdu-Chongqing urban *** sequestration service flow and climate regulation service flow were the highest in the middle reaches of the Yangtze River Basin and the urban agglomeration in the middle reaches of the Yangtze River.3)From 2000 to 2020,the change ratios of the area proportion of the confluence,flow,and outflow areas in the Yangtze River Basin were 1.06,3.17,and 0.86,*** results of this research could offer decision support for regulating ecosystem services in the Yangtze River Basin,promoting sustainable regional development and achieving rational use of the basin resources.

关键词： Yangtze River Basin ecosystem services supply and demand service flow quantitative assessment spatial matching

Zircon Hf Isotope Mapping for Understanding Crustal Architecture and Its Controls on Mineralization during Early Cretaceous in the Southern Great Xing'an Range,NE China

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Journal of Earth Science 2024年第1期35卷 41-50页

作者： Feng Yuan Huanan Liu Shengjin Zhao Mingjing fan State Key Laboratory of Geological Processes and Mineral Resources Collaborative Innovation Center for Exploration of Strategic Mineral ResourcesSchool of Earth ResourcesChina University of GeosciencesWuhan 430074China State Key Laboratory of Geological Processes and Mineral Resources School of Earth Sciences and ResourcesChina University of GeosciencesBeijing100083China No.10 Institute of Geological Exploration Inner Mongolia Bureau of Geology and Mineral ResourcesChifeng 024000China Key Laboratory of Metallogeny and Mineral Assessment Institute of Mineral ResourcesChinese Academy of Geological SciencesBeijing 100037China

Voluminous Early Cretaceous granitoids and associated large-scale ore deposits are distributed within the southern Great Xing'an Range(SGXR),NE *** on previously published geochronology and zircon Hf-isotope data,Hf isotope mapping is undertaken to improve our understanding of crustal architecture and its controls on ore *** ore-related Early Cretaceous granitoids were sourced predominantly from juvenile crust,with the involvement of variable proportions of ancient crustal *** crustal architecture,as inferred from Hf isotopic contour maps,indicates two distinct Hf isotopic domains in SGXR,including(1)a higher-ε_(Hf)(+7 to+11)juvenile crust containing minor ancient crustal material,and(2)a lower-ε_(Hf)(+2 to+6)juvenile crust containing a greater proportion of ancient crustal *** Hf isotopic maps identify links between crustal architecture and regional *** deposits and other deposits with significant Cu production are restricted mainly to the higher-ε_(Hf)juvenile crustal regions in the northern and eastern *** dominated by other metals(e.g.,Mo,Sn,W,Pb,Zn,and Ag)occur mainly in the lower-ε_(Hf)juvenile crustal regions in the southern and western *** between juvenile crust-derived melts and ancient crustal components played an important role on the distribution of various ore metals.

关键词： Hf isotope mapping crustal architecture large-scale Early Cretaceous granitoids distribution of ore deposits southern Great Xing'an Range zircon

Epileptic brain network mechanisms and neuroimaging techniques for the brain network

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Neural Regeneration Research 2024年第12期19卷 2637-2648页

作者： Yi Guo Zhonghua Lin Zhen fan Xin Tian Department of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Sichuan Provincial Center for Mental Health Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Geriatrics Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurology Chongqing Key Laboratory of NeurologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Epilepsy can be defined as a dysfunction of the brain network,and each type of epilepsy involves different brain-network changes that are implicated diffe rently in the control and propagation of interictal or ictal *** more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical *** increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tra ctography,diffusion kurtosis imaging-based fiber tractography,fiber ball imagingbased tra ctography,electroencephalography,functional magnetic resonance imaging,magnetoencephalography,positron emission tomography,molecular imaging,and functional ultrasound imaging have been extensively used to delineate epileptic *** this review,we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy,and extensively analyze the imaging mechanisms,advantages,limitations,and clinical application ranges of each technique.A greater focus on emerging advanced technologies,new data analysis software,a combination of multiple techniques,and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

关键词： electrophysiological techniques epilepsy functional brain network functional magnetic resonance imaging functional near-infrared spectroscopy machine leaning molecular imaging neuroimaging techniques structural brain network virtual epileptic models

Plant RNA-binding proteins:Phase separation dynamics and functional mechanisms underlying plant development and stress responses

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Molecular Plant 2024年第4期17卷 531-551页

作者： Sheng fan Yu Zhang Shaobo Zhu Lisha Shen Temasek Life Sciences Laboratory 1 Research LinkNational University of Singapore1 Research LinkSingapore 117604Singapore Department of Biological Sciences National University of Singapore14 Science Drive 4Singapore 117543Singapore

RNA-binding proteins(RBPs)accompany RNA from synthesis to decay,mediating every aspect of RNA metabolism and impacting diverse cellular and developmental processes in *** RBPs undergo phase separation along with their bound RNA to form and function in dynamic membraneless biomolecular condensates for spatiotemporal coordination or regulation of RNA *** evidence suggests that phase-separating RBPs with RNA-binding domains and intrinsically disordered regions play important roles in plant development and stress ***,we summarize the current knowledge about how dynamic partitioning of RBPs into condensates controls plant development and enables sensing of experimental changes to confer growth plasticity under stress conditions,with a focus on the dynamics and functional mechanisms of RBP-rich nuclear condensates and cytoplasmic granules in mediating RNA *** also discuss roles of multiple factors,such as environmental signals,protein modifications,and N6-methyladenosine RNA methylation,in modulating the phase separation behaviors of RBPs,and highlight the prospects and challenges for future research on phase-separating RBPs in crops.

关键词： RNA-binding proteins phase separation biomolecular condensates RNA metabolism development stress resilience

Persistent mixing bursts in the equatorial Pacific thermocline induced by persistent equatorial waves

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Journal of Oceanology and Limnology 2024年第2期42卷 492-510页

作者： Jingjing ZHANG Chuanyu LIU Xiang GONG fan WANG School of Mathematics and Physics Qingdao University of Science and TechnologyQingdao 266100China Key Laboratory of Ocean Circulation and Waves Institute of OceanologyChinese Academy of SciencesQingdao 266071China Laoshan Laboratory Qingdao 266237China

A recent study by Liu et al.(2020)suggested that due to the saturation of equatorially trapped planetary waves with different dynamical types,temporal periods,meridional and baroclinic modes,complex layer structures of vertical velocity shear and hence turbulent mixing could frequently occur in the thermocline of the eastern equatorial *** investigated the occurrence of the interior turbulent mixing as indicated by shear instabilities,above the Equatorial Undercurrent(EUC)core at three equatorial sites along 140°W,170°W,and 165°E,respectively,based mainly on data from the Tropical Atmosphere and Ocean(TAO)mooring *** found that turbulent mixing bursts persisted in the thermocline of all three ***,the interior turbulent mixing layers(ITMLs)could occur in probability of approximately 68%,53%,and 48%at the three sites,*** overall occurrence probability shows obvious and similar biannual variations at 140°W and 170°W,which is higher in boreal from late summer to winter and lower in ***,the ITMLs are primarily located above the EUC core and prevail in deeper(shallower)layers from late summer to winter(spring).Most ITMLs(70%)lasted for hours to 3 days,and a few of them(15%)for more than 7 *** thicknesses of ITMLs were concentrated between 15 and 55 *** 165°E,the vertical distribution of ITML occurrence probability was different from that at 140°W and 170°W,as it did not show a preference for depths;the durations of ITMLs are short(also from hours to several days)and their thicknesses were between 5 and 25 *** properties,particularly the high occurrence probability,and short durations demonstrated the persistence of thermocline mixing in the western to eastern equatorial Pacific thermocline and confirmed the generation mechanism by persistent equatorial waves as well.

关键词： interior turbulent mixing layer(ITML) weakly sheared layer(WSL) Equatorial Undercurrent(EUC)core occurrence probability seasonality

Associative Tasks Computing Offloading Scheme in Internet of Medical Things with Deep Reinforcement Learning

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China Communications 2024年第4期21卷 38-52页

作者： Jiang fan Qin Junwei Liu Lei Tian Hui School of Communications and Information Engineering Xi’an University of Posts and TelecommunicationsXi’an 710121China State Key Laboratory of Networking and Switching Technology Beijing University of Posts and TelecommunicationsBeijing 100876China

The Internet of Medical Things(Io MT) is regarded as a critical technology for intelligent healthcare in the foreseeable 6G era. Nevertheless, due to the limited computing power capability of edge devices and task-related coupling relationships, Io MT faces unprecedented challenges. Considering the associative connections among tasks, this paper proposes a computing offloading policy for multiple-user devices(UDs) considering device-to-device(D2D) communication and a multi-access edge computing(MEC)technique under the scenario of Io MT. Specifically,to minimize the total delay and energy consumption concerning the requirement of Io MT, we first analyze and model the detailed local execution, MEC execution, D2D execution, and associated tasks offloading exchange model. Consequently, the associated tasks’ offloading scheme of multi-UDs is formulated as a mixed-integer nonconvex optimization problem. Considering the advantages of deep reinforcement learning(DRL) in processing tasks related to coupling relationships, a Double DQN based associative tasks computing offloading(DDATO) algorithm is then proposed to obtain the optimal solution, which can make the best offloading decision under the condition that tasks of UDs are associative. Furthermore, to reduce the complexity of the DDATO algorithm, the cacheaided procedure is intentionally introduced before the data training process. This avoids redundant offloading and computing procedures concerning tasks that previously have already been cached by other UDs. In addition, we use a dynamic ε-greedy strategy in the action selection section of the algorithm, thus preventing the algorithm from falling into a locally optimal solution. Simulation results demonstrate that compared with other existing methods for associative task models concerning different structures in the Io MT network, the proposed algorithm can lower the total cost more effectively and efficiently while also providing a tradeoff between delay and energy co

关键词： associative tasks cache-aided procedure double deep Q-network Internet of Medical Things(IoMT) multi-access edge computing(MEC)

Dynamic response of buildings under debris flow impact

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Journal of Mountain Science 2024年第5期21卷 1581-1597页

作者： LIU Huan fan Xiaoyi TIAN Shujun DENG Xin School of Mechanical and Electrical Engineering Southwest Petroleum UniversityChengdu 610500China School of Civil Engineering and Geomatics Southwest Petroleum UniversityChengdu 610500China Housing and Urban-Rural Development Bureau of Mingshan District Ya’an 625100China Engineering Safety Assessment and Protection Research Southwest Petroleum UniversityChengdu 610500China School of Civil Engineering and Architecture Southwest University of Science and TechnologyMianyang 621010China

This study employs the smoothed particle hydrodynamics–finite element method(SPH–FEM) coupling numerical method to investigate the impact of debris flow on reinforced concrete(RC)-frame buildings. The methodology considers the variables of debris flow depth and velocity and introduces the intensity index IDV(IDV = DV) to evaluate three different levels of debris flow impact intensity. The primary focus of this study is to investigate the dynamic response and failure mechanism of RC-frame buildings under debris flow impact, including structural failure patterns, impact force and column displacement. The results show that under a highintensity impact, a gradual collapse process of the RCframe building can be observed, and the damage mode of the frame column reflects shear failure or plastic hinge failure mechanism. First, the longitudinal infill walls are damaged owing to their low out-of-plane flexural capacity;the critical failure intensity index IDV value is approximately 7.5 m2/s. The structure cannot withstand debris flows with an intensity index IDV greater than 16 m2/s, and it is recommended that the peak impact force should not exceed 2100 k N. The impact damage ability of debris flow on buildings mostly originates from the impact force of the frontal debris flow, with the impact force of the debris flow body being approximately 42% lower than that of the debris flow head. Finally, a five-level classification system for evaluating the damage status of buildings is proposed based on the numerical simulation and investigation results of the disaster site.

关键词： SPH–FEM method Debris flow Buildings The intensity index Dynamic response