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NF-κB in biology and targeted therapy:new insights and translational implications

Signal Transduction and Targeted Therapy 2024年第4期9卷 1322-1358页

作者： Qing guo Yizi Jin Xinyu Chen Xiaomin Ye Xin Shen Mingxi Lin Cheng Zeng Teng zhou jian Zhang Department of Medical Oncology Fudan University Shanghai Cancer CenterNo.270Dong'an RoadShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina State Key Laboratory of Oncogenes and Related Genes Renj-Med-X Stem Cell Research CenterShanghai Cancer Institute&Department of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127PR China Department of Cardiology the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan 2nd RoadGuangzhou 510080China Department of Neurology Rujin HospitalShanghai JiaoTong University Schoolof MedicineShanghaiChina

NF-κB signaling has been discovered for nearly 40 years.Initially,NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses.However,with extensive and in-depth investigations,researchers have discovered that its role can be expanded to a variety of signaling mechanisms,biological processes,human diseases,and treatment options.In this review,we first scrutinize the research process of NF-κB signaling,and summarize the composition,activation,and regulatory mechanism of NF-κB signaling.We investigate the interaction of NF-κB signaling with other important pathways,including PI3K/AKT,MAPK,JAK-STAT,TGF-β,Wnt,Notch,Hedgehog,and TLR signaling.The physiological and pathological states of NF-κB signaling,as well as its intricate involvement in inflammation,immune regulation,and tumor microenvironment,are also explicated.Additionally,we illustrate how NF-κB signaling is involved in a variety of human diseases,including cancers,inflammatory and autoimmune diseases,cardiovascular diseases,metabolic diseases,neurological diseases,and covID-19.Further,we discuss the therapeutic approaches targeting NF-κB signaling,including IKK inhibitors,monoclonal antibodies,proteasome inhibitors,nuclear translocation inhibitors,DNA binding inhibitors,TKls,non-coding RNAs,immunotherapy,and CAR-T.Finally,we provide an outlook for research in the field of NF-κB signaling.We hope to present a stereoscopic,comprehensive NF-κB signaling that will inform future research and clinical practice.

关键词： PI3K/AKT diseases involvement

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Harnessing data using symbolic regression methods for discovering novel paradigms in physics

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 1-11页

作者： jianyang guo Wan-jian Yin College of Energy Soochow Institute for Energy and Materials Innovations(SIEMIS)Jiangsu Provincial Key Laboratory for Advanced Carbon Materials and Wearable Energy TechnologiesSoochow UniversitySuzhou 215006China Shanghai Qi Zhi Institute Shanghai 200232China Light Industry Institute of Electrochemical Power Sources Soochow UniversitySuzhou 215006China

In recent years,machine-learning methods have profoundly impacted research in the interdisciplinary fields of physics.However,most machine-learning models lack interpretability,and physicists doubt the credibility of their conclusions because they cannot be combined with prior physical knowledge.Therefore,this review focuses on symbolic regression,which is an interpretable machine-learning method.First,the relevant concepts of machine learning are introduced in conjunction with induction.Next,we provide an overview of symbolic regression methods.Subsequently,the recent directions for the application of symbolic regression methods in different subfields of physics are outlined,and an overview of the ways in which the applications of symbolic regression have evolved in the realm of physics is provided.The major aim of this review is to introduce the basic principles of symbolic regression and explain its applications in the field of physics.

关键词： machine learning genetic programming symbolic regression

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Plutonium utilization in a small modular molten-salt reactor based on a batch fuel reprocessing scheme

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Nuclear Science and Techniques 2024年第4期35卷 15-28页

作者： Xue-Chao Zhao Rui Yan Gui-Feng Zhu Ya-Fen Liu jian guo Xiang-zhou Cai Yang Zou Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201800China CAS Innovative Academies in TMSR Energy System Chinese Academy of SciencesShanghai 201800China University of Chinese Academy of Sciences Beijing 100049China

A molten salt reactor(MSR)has outstanding features considering the application of thorium fuel,inherent safety,sustainability,and resistance to proliferation.However,fissile material^(233)U is significantly rare at the current stage,thus it is difficult for MSR to achieve a pure thorium-uranium fuel cycle.Therefore,using plutonium or enriched uranium as the initial fuel for MSR is more practical.In this study,we aim to verify the feasibility of a small modular MSR that utilizes plutonium as the starting fuel(SM-MSR-Pu),and highlight its advantages and disadvantages.First,the structural design and fuel management scheme of the SM-MSR-Pu were presented.Second,the neutronic characteristics,such as the graphite-irradiation lifetime,burn-up performance,and coefficient of temperature reactivity were calculated to analyze the physical characteristics of the SM-MSR-Pu.The results indicate that plutonium is a feasible and advantageous starting fuel for a SM-MSR;however,there are certain shortcomings that need to be solved.In a 250 MWth SM-MSR-Pu,approximately 288.64 kg^(233)U of plutonium with a purity of greater than 90% is produced while 978.00 kg is burned every ten years.The temperature reactivity coefficient decreases from -4.0 to -6.5 pcm K^(-1) over the 50-year operating time,which ensures a long-term safe operation.However,the amount of plutonium and accumulation of minor actinides(MAs)would increase as the burn-up time increases,and the annual production and purity of^(233)U will decrease.To achieve an optimal burn-up performance,setting the entire operation time to 30 years is advisable.Regardless,more than 3600 kg of plutonium eventually accumulate in the core.Further research is required to effectively utilize this accumulated plutonium.

关键词： Molten salt fuel Plutonium utilization ^(233)U TRUs mole fraction Temperature feedback coefficient

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Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 77-82页

作者： Wen-jian Mao Jing zhou guo-Fu Zhang Fa-Xi Chen Jing-Zhu Zhang Bai-Qiang Li Lu Ke Wei-Qin Li Department of Critical Care Medicine Jinling HospitalNanjing Medical UniversityNanjing 210002China Department of Critical Care Medicine Jinling HospitalMedical School of Nanjing UniversityNanjing 210002China National Institute of Healthcare Data Science Nanjing UniversityNanjing 210010China

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

关键词： Anticoagulation Splanchnic venous thrombosis Acute necrotizing pancreatitis Readmission Long-term outcomes

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Influence of Electroshocking Treatment on Microstructure and Mechanical Properties of Ti-6.5Al-3.5Mo-1.5Zr-0.3Si Thin-Wall Specimen Manufactured by Laser Melting Deposition

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Acta Metallurgica Sinica(English Letters) 2024年第1期37卷 145-158页

作者： Yan Wen Xuan Sun jian zhou Bingliang Liu Haojie guo Yuxin Li Fei Yin Liqiang Wang Lechun Xie Lin Hua Hubei Key Laboratory of Advanced Technology for Automotive Components Wuhan University of TechnologyWuhan430070China Hubei Collaborative Innovation Center for Automotive Components Technology Wuhan430070China Hubei Longzhong Laboratory Xiangyang441000China Shanghai Aircraft Manufacturing Co. Ltd.Commercial Aircraft Corporation of ChinaLtd.Shanghai201324China State Key Laboratory of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong UniversityShanghai200240China

In order to improve the properties of titanium alloys manufactured by laser melting deposition(LMD),the electroshocking treatment(EST)was proposed in this work.The effects of EST on microstructure and mechanical properties of LMD Ti-6.5Al-3.5Mo-1.5Zr-0.3Si were investigated.The results showed that the width of the heat affected band decreased and disappeared under the thermal and athermal effects of EST,resulting in the uniform microstructure.In the microstructure,theαlaths became coarser gradually,and the quantity ofα/βinterface was reduced.The reduction of the quantity ofα/βinterface leads to make less resistant to dislocation,resulting in the reduction in hardness and strength.The discontinuous grain boundaryαphase and nucleationαcolony near grain boundary inhibited the crack propagation and improved the ductility.Summary,EST can manipulate the microstructure and improve the mechanical properties of LMD titanium alloys.

关键词： Electroshocking treatment(EST) Laser melting deposition(LMD) Titanium alloy Microstructure Mechanical properties

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In-situ SEM characterization of fracture mechanism of TiB/Ti-2Al-6Sn titanium matrix composites after electroshocking treatment

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Rare Metals 2024年第6期43卷 2805-2818页

作者： Ya-Ya Wu jian zhou guo-Lei Han Yan Wen zhou Wang Li-Qiang Wang Wei-Jie Lv Le-Chun Xie Lin Hua Hubei Key Laboratory of Advanced Technology for Automotive Components Wuhan University of Technology Hubei Collaborative Innovation Center for Automotive Components Technology Faculty of Materials and Manufacturing Beijing University of Technology State Key Laboratory of Metal Matrix Composites School of Materials Science and EngineeringShanghai Jiao Tong University

In this article,in-situ scanning electron microscope characterization of the tensile properties of TiB/Ti-2Al-6Sn titanium matrix composite(TMC) was conducted before and after electroshocking treatment(EST).After EST,the tensile strength increased by 113.2 MPa.The effect of EST on the tensile strength and fracture behavior of TiB was investigated using in-situ characterization of the fracture morphology and crack propagation path of the matrix and TiB.Before EST,TiB fracture introduced cracks that extended into the matrix,resulting in material failure.After EST,the refined TiB improved the bearing capacity of the matrix,thereby improving TMC strength.Moreover,after EST,the cracks were introduced into the matrix,and resulting the fracture of matrix first.With an increase in the external load,cracks in the matrix were observed to propagate to TiB,and the refined TiB was fractured,detached,and pulled out,resulting in the formation of pores.Analyzing the propagation path of the main crack after EST showed that the deflection angle of the main crack increased.The micro structure of the fracture surface indicated that the fracture of the matrix was plastic,whereas that of TiB was brittle.After EST,the size and area of the dimples increased,confirming the increase in plasticity.The results revealed that the comprehensive mechanical properties of TiB/Ti-2Al-6Sn improved after EST.Hence,EST is an efficient method for tailoring the micro structures and mechanical properties of TMCs.

关键词： TiB/Ti-2Al-6Sn In-situ microstructure characterization Tensile properties Reinforcement Electroshocking treatment (EST)

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Silkworm pupa peptide ameliorates dextrose sodium sulfate-induced colitis by enhancing gut barriers and modifying gut flora

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Food Science and Human Wellness 2024年

作者： Yaxi zhou Diandian Wang Hao Duan Shiqi zhou Jinhong guo Yu guo jian Zhao Wenjie Yan Beijing Key Laboratory of Bioactive Substances and Functional Food College of Biochemical Engineering Beijing Union University

The anti-inflammatory properties of silkworm pupa peptide (SPP) have been recognized for their potential benefits in colitis treatment. However， the underlying mechanism of SPP in colitis animal models remains unclear. The objective of our work was to investigate the improving effect and the mechanism of action of SPP on a mouse model of dextrose sodium sulfate (DSS)-induced colitis. The findings suggested that SPP effectively eased ulcerative colitis (UC) symptoms in mice by decreasing disease activity index， ameliorating histopathological injury， and decreasing serum and colonic markers of inflammation. In addition， our research findings demonstrated that SPP restored intestinal barrier function by increasing the production of tight junction proteins such as zonula occludens-1 (ZO-1)， claudin-1， claudin-3， occludin， and adherens junction protein E-cadherin1. Further， SPP supplementation enhanced the concentration of short-chain fatty acids and positively altered the makeup of the gut bacteria in the mice’s gut. These findings underscore SPP’s ability to slow the progression of colitis and point to its possible use as a functional component in dietary supplements for the prevention of early-stage colitis.

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Variability Analysis for a Two-station Queueing Network in Heavy Traffic with Arrival Processes Driven by Queues

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Acta Mathematicae Applicatae Sinica 2024年第2期40卷 445-466页

作者： jian CAO Yong-jiang guo Kai-ming YANG School of Science Beijing University of Posts and TelecommunicationsBeijing 100876China

The law of the iterated logarithm(LIL)for the performance measures of a two-station queueing network with arrivals modulated by independent queues is developed by a strong approximation method.For convenience,two arrival processes modulated by queues comprise the external system,all others are belong to the internal system.It is well known that the exogenous arrival has a great influence on the asymptotic variability of performance measures in queues.For the considered queueing network in heavy traffic,we get all the LILs for the queue length,workload,busy time,idle time and departure processes,and present them by some simple functions of the primitive data.The LILs tell us some interesting insights,such as,the LILs of busy and idle times are zero and they reflect a small variability around their fluid approximations,the LIL of departure has nothing to do with the arrival process,both of the two phenomena well explain the service station’s situation of being busy all the time.The external system shows us a distinguishing effect on the performance measures:an underloaded(overloaded,critically loaded)external system affects the internal system through its arrival(departure,arrival and departure together).In addition,we also get the strong approximation of the network as an auxiliary result.

关键词： two-station queueing network the law of the iterated logarithm(LIL) strong approximation fluid approximation

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Polarization-dependent photoinduced metal–insulator transitions in manganites

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Science Bulletin 2024年第2期69卷 183-189页

作者： Lina Deng Weiye Zhang Hanxuan Lin Lifen Xiang Ying Xu Yadi Wang Qiang Li Yinyan Zhu Xiaodong zhou Wenbin Wang Lifeng Yin Hangwen guo Chuanshan Tian jian Shen State Key Laboratory of Surface Physics Institute for Nanoelectronic Devices and Quantum Computingand Department of PhysicsFudan UniversityShanghai 200433China Shanghai Research Center for Quantum Sciences Shanghai 201315China Zhangjiang Fudan International Innovation Center Fudan UniversityShanghai 201210China Collaborative Innovation Center of Advanced Microstructures Nanjing 210093China Shanghai Branch CAS Center for Excellence and Synergetic Innovation Center in Quantum Information and Quantum PhysicsShanghai 201315China

In correlated oxides,collaborative manipulation on light intensity,wavelength,pulse duration and polarization has yielded many exotic discoveries,such as phase transitions and novel quantum states.In view of potential optoelectronic applications,tailoring long-lived static properties by light-induced effects is highly desirable.So far,the polarization state of light has rarely been reported as a control parameter for this purpose.Here,we report polarization-dependent metal-to-insulator transition(MIT)in phaseseparated manganite thin films,introducing a new degree of freedom to control static MIT.Specifically,we observed giant photoinduced resistance jumps with striking features:(1)a single resistance jump occurs upon a linearly polarized light incident with a chosen polarization angle,and a second resistance jump occurs when the polarization angle changes;(2)the amplitude of the second resistance jump depends sensitively on the actual change of the polarization angles.Linear transmittance measurements reveal that the origin of the above phenomena is closely related to the coexistence of anisotropic micro-domains.Our results represent a first step to utilize light polarization as an active knob to manipulate static phase transitions,pointing towards new pathways for nonvolatile optoelectronic devices and sensors.

关键词： Metal-insulator phase transitions Polarization of light Electronic phase separation Selective domain controllability

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Neoantigen cancer vaccines:a new star on the horizon

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Cancer Biology & Medicine 2024年第4期21卷 274-311页

作者： Xiaoling Li jian You Liping Hong Weijiang Liu Peng guo Xishan Hao Cell Biotechnology Laboratory Tianjin Cancer Hospital Airport HospitalTianjin 300308China National Clinical Research Center for Cancer Tianjin 300060China Haihe Laboratory of Synthetic Biology Tianjin 300090China Department of Thoracic Oncology Tianjin Cancer Hospital Airport HospitalTianjin 300308China Department of Thoracic Oncology Surgery Tianjin Medical University Cancer Institute&HospitalTianjin 300060China Tianjin Medical University Cancer Institute&Hospital Tianjin 300060China

Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.

关键词： Immunotherapy neoantigen cancer vaccine solid tumors high-throughput sequencing bioinformatics PDOs AI HLA TCR

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