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Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

Cancer Communications 2024年第3期44卷 297-360页

作者： Bin Song ping Yang Shuyu zhang Laboratory of Radiation Medicine West China Second University HospitalSichuan UniversityChengduSichuanP.R.China The Second Affiliated Hospital of Chengdu Medical College China National Nuclear Corporation 416 HospitalChengduSichuanP.R.China Laboratory of Radiation Medicine NHC Key Laboratory of Nuclear Technology Medical TransformationWest China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengduSichuanP.R.China

Cancer is a leading cause of death worldwide.Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiother-apy as well as immunotherapy have benefited cancer patients considerably.Tumor protein p53(TP53),a crucial tumor suppressor gene encoding p53,reg-ulates numerous downstream genes and cellular phenotypes in response to various stressors.The affected genes are involved in diverse processes,includ-ing cell cycle arrest,DNA repair,cellular senescence,metabolic homeostasis,apoptosis,and autophagy.However,accumulating recent studies have contin-ued to reveal novel and unexpected functions of p53 in governing the fate of tumors,for example,functions in ferroptosis,immunity,the tumor microenvi-ronment and microbiome metabolism.Among the possibilities,the evolutionary plasticity of p53 is the most controversial,partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 signaling.Nearly 40 years after its discovery,this key tumor suppressor remains somewhat enigmatic.The intricate and diverse functions of p53 in reg-ulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology,which has been painstak-ingly revealed.Additionally,TP53 mutation is one of the most significant genetic alterations in cancer,contributing to rapid cancer cell growth and tumor pro-gression.Here,we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies,including chemotherapy,radiotherapy,and immunotherapy.Furthermore,we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.

关键词： cancer chemotherapy drug targeting immunotherapy p53 tumor suppressor

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FPGA-based position reconstruction method for neutron beam flux spatial distribution measurement in BNCT

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Nuclear Science and Techniques 2024年第3期35卷 96-108页

作者： Wei Jiang ping Cao yi-Ming Wu Xian-Ke Liu Zhu-Jun Fang Zhi-Yong zhang Bin Shi Jun Chen State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China Department of Modern Physics University of Science and Technology of ChinaHefei 230026China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230026China National Key Laboratory for Metrology and Calibration Techniques China Institute of Atomic EnergyBeijing 102413China

A new measurement method for the spatial distribution of neutron beam flux in boron neutron capture therapy(BNCT)is being developed based on the two-dimensional Micromegas detector.To address the issue of long processing times in traditional offline position reconstruction methods,this paper proposes a field programmable gate array based online position reconstruction method utilizing the micro-time projection chamber principle.This method encapsulates key technical aspects:a self-adaptive serial link technique built upon the dynamical adjustment of the delay chain length,fast sorting,a coordinate-matching technique based on the mapping between signal timestamps and random access memory(RAM)addresses,and a precise start point-merging technique utilizing a circular combined RAM.The performance test of the selfadaptive serial link shows that the bit error rate of the link is better than 10-12 at a confidence level of 99%,ensuring reliable data transmission.The experiment utilizing the readout electronics and Micromegas detector shows a spatial resolution of approximately 1.4 mm,surpassing the current method’s resolution level of 5 mm.The beam experiment confirms that the readout electronics system can obtain the flux spatial distribution of neutron beams online,thus validating the feasibility of the position reconstruction method.The online position reconstruction method avoids traditional methods,such as bubble sorting and traversal searching,simplifies the design of the logic firmware,and reduces the time complexity from O(n2)to O(n).This study contributes to the advancement in measuring neutron beam flux for BNCT.

关键词： Position reconstruction FPGA Readout electronics Neutron flux spatial distribution

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Chemoselective and Living/Controlled Polymerization of Alkenyl Methacrylates by the Phosphonium Ylide/Organoaluminum Lewis Pairs

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Chinese Journal of Polymer Science 2024年第2期42卷 159-167,I0005页

作者： Zhi-Kang Chen Wu-Chao Zhao yi-Ling Zhao Cong-Lei Liu Liu-yin Jiang Yue-Tao zhang Hong-ping Zhu State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringXiamen UniversityXiamen361005China State Key Laboratory of Supramolecular Structure and Materials College of ChemistryJilin UniversityChangchun130012China

Chemoselective,living/controlled polymerizations of allyl methacrylate(AMA) and vinyl methacrylate(VMA) with/without methyl methacrylate(MMA) by using the phosphonium ylide/organoaluminum based Lewis pairs(LPs) have been realized.The P-ylide-2/AIMe(BHT)_(2)(Pylide-2=Ph_(3)P=CHMe and BHT=2,6-iBu_(2)-4-MeC_(6)H_(2)O) was demonstrated to be superior by which homopolymers PAMAs(M_(n)=27.6-111.5kg/mol and ■=1.14-1.25) and PVMAs(M_(n)=28.4-78.4 kg/mol and ■=1.12-1.18) and block copolymers PMMA-b-PAMA,PAMA-b-PVMA,PAMA-bPMMA,PMMA-b-PAMA-b-PMMA,PAMA-b-PMMA-b-PAMA,and PAMA-b-PVMA-b-PAMA were synthesized.In the polymerizations,all of the monomers were reacted by the conjugated ester vinyl groups leaving intactly the nonconjugated acryloxy groups.The pendant acryloxy groups attached to the main chain enable further to post-functionalization by the AIBN-induced radical "thiol-ene" reaction using PhCH_(2)SH.The thiolether side group-containing polymers PAMA-SCH_(2)Ph and PAMA-SCH_(2)Ph-b-PMMA-b-PAMA-SCH_(2)Ph were thus prepared.

关键词： Phosphonium ylide Alkenyl methacrylate Chemoselectivity Living/controlled polymerization Post-functionalization

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Gabapentinoids for the treatment of stroke

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Neural Regeneration Research 2024年第7期19卷 1509-1516页

作者： ying zhang Chenyu zhang Xiaoli yi Qi Wang Tiejun zhang Yuwen Li Department of Pharmacy West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Neurosurgery West China HospitalSichuan UniversityChengduSichuan ProvinceChina

Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.

关键词： cortical spreading depolarization gabapentinoid intracerebral hemorrhage pain after stroke stroke subarachnoid hemorrhage

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Essential Players in Cooperative Games with Graph Communication Structure

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Journal of the Operations Research Society of China 2024年第1期12卷 93-108页

作者： Guang zhang Jing-yi Ge Business School University of Shanghai for Science and TechnologyShanghai200093China

A class of cooperative games with graph communication structure is studied in this paper by considering some important players,namely essential players.Under the assumption that only connected coalitions containing essential players are able to cooperate and obtain their worths,the class of graph games with essential players is proposed as well as an allocation rule.The proposed value follows the spirit of the Myerson value defined by applying the Shapley value on a modified game.Three properties,feasible component efficiency,the inessential component property,and fairness,are provided to fully characterize this value,where feasible component efficiency and fairness follows the same ideas of component efficiency and fairness for classical graph games,and the inessential component property says that the total payoffs of the players in a non-feasible component is zero.Moreover,some computational aspects of the proposed value and comparisons with disjunctive permission value for games with permission structure are also studied,respectively.

关键词： Cooperative game Graph structure Essential player Myerson value Computation Permission structure

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Manufacturing CAR-NK against tumors: Who is the ideal supplier?

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Chinese Journal of Cancer Research 2024年第1期36卷 1-16页

作者： Feifei Guo yi zhang Jiuwei Cui The First Hospital of Jilin University Cancer CenterChangchun 133021China

Chimeric antigen receptor-natural killer(CAR-NK) cells have emerged as another prominent player in the realm of tumor immunotherapy following CAR-T cells. The unique features of CAR-NK cells make it possible to compensate for deficiencies in CAR-T therapy, such as the complexity of the manufacturing process, clinical adverse events, and solid tumor challenges. To date, CAR-NK products from different allogeneic sources have exhibited remarkable anti-tumor effects on preclinical studies and have gradually been applied in clinical practice.However, each source has advantages and disadvantages. Selecting a suitable source may help maximize CAR-NK cell efficacy and increase the feasibility of clinical transformation. Therefore, this review discusses the development and challenges of CAR-NK cells from different sources to provide a reference for future exploration.

关键词： CAR-NK cells cord blood iPSC NK-92 cells peripheral blood

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Influence of the Acoustic Liner in Large Eddy Simulation of Longitudinal Thermoacoustic Instability in a Model Annular Combustor

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Journal of Thermal Science 2024年第2期33卷 710-724页

作者： MENG Sheng zhang Man GAO yi AECC Commercial Aircraft Engine Co. Ltd.Shanghai200241China School of Aeronautics and Astronautics Shanghai Jiao Tong UniversityShanghai200240China

Although extensive efforts have been made to dampen the thermoacoustic instability,successfully controlling the pressure oscillations in modern gas turbines or aeroengines remains challenging.The influence of the acoustic liner on the longitudinal thermoacoustic mode in a model annular combustor is investigated by Large Eddy Simulation(LES) in this work.The result of the self-excited longitudinal thermoacoustic instability without the liner agrees well with the frequency and acoustic analysis of the pressure mode based on experimental data.Three different bias flow velocities of the liner located downstream of the combustor are then simulated.The results reveal that the existence of the liner influences not only the acoustic field but also the flow field.When the bias velocity is large,it leads to intense turbulence-induced fluctuations,and the pressure oscillation is modulated intermittently.It shows that the weak coupling between flow and pressure oscillations plays a significant role in the onset of the intermittency of a thermoacoustic system.Based on the dynamic analysis of the thermoacoustic system with the acoustic liner,this intermittency is caused by the influence of the flow field on the flame-acoustic coupling.Finally,a low-order modeling method based on Van der Pol(VdP) oscillator with additive stochastic forcing is conducted to reproduce the evolving dynamics of the thermoacoustic system.Although the numerical cases demonstrated in this work are relatively simpler than those in a practical combustion system,the results are helpful for us to understand the effect of the acoustic liner and show the attractive potential to apply this device to suppress thermoacoustic instability.

关键词： thermoacoustic instability acoustic liner Large Eddy Simulation low-order modeling

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Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2271-2283页

作者： Long-Chen Yu Ya-ping Li Yue-Ming Xin Mai Mao Ya-Xin Pan yi-Xuan Qu Zheng-Dong Luo yi zhang Xin zhang Department of Clinical Laboratory Qilu Hospital of Shandong UniversityShandong Engineering Research Center of Biomarker and Artificial Intelligence ApplicationJinan 250012Shandong ProvinceChina

The morbidity and mortality of gastrointestinal(GI)malignancies are among the highest in the world,posing a serious threat to human health.Because of the insidious onset of the cancer,it is difficult for patients to be diagnosed at an early stage,and it rapidly progresses to an advanced stage,resulting in poor treatment and prognosis.Fusobacterium nucleatum(F.nucleatum)is a gram-negative,sporefree anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal,esophageal,gastric,and pancreatic cancers via various intricate mechanisms.Recent development in novel research suggests that F.nucleatum may function as a biomarker in GI malignancies.Detecting the abundance of F.nucleatum in stool,saliva,and serum samples of patients may aid in the diagnosis,risk assessment,and prognosis monitoring of GI malignancies.This editorial systematically describes the biological roles and mechanisms of F.nucleatum in GI malignancies focusing on the application of F.nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F.nucleatum and GI tumors-related research.

关键词： Gastrointestinal malignancies Fusobacterium nucleatum Biomarker Diagnosis Prognosis

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Regulated polarization degree of upconversion luminescence and multiple anti-counterfeit applications

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Rare Metals 2024年第5期43卷 2172-2183页

作者： Dong-ping Wen ping Chen yi Liang Xiao-Ming Mo Cao-Feng Pan Center On Nanoenergy Research Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and Technology Guangxi University Key Laboratory of Micronano Energy and Sensor CAS Center for Excellence in Nanoscience Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences

Polarization upconversion luminescence（PUCL） of lanthanide ions (Ln3+) has been widely used in single particle tracking,microfluidics detection,three-dimensional displays,and so on.However,no effective strategy has been developed for modulating PUCL.Here we report a strategy to regulate PUCL in Ho3+-doped NaYF4single nanorods based on the number of upconversion photons.By constructing a multiphoton upconversion system for Ho3+,we regulate the degree of polarization （DOP） of PUCL from 0.590 for two-photon luminescence to 0.929 for three-photon upconversion luminescence （UCL）.Furthermore,our strategy is verified from cross-relaxation between Ho3+and Yb3+,excitation wavelength,excitation power density,and local site symmetry.And this regulation strategy of PUCL has also been achieved in Tm3+,with the DOP ranging from 0.233 for two-photon luminescence to 0.925 for four-photon UCL Besides,multi-dimensional anti-counterfeiting display has been explored with PUCL.This work provides an effective strategy for regulating PUCL and also provides more opportunities for the development of polarization display optical encoding,anti-counterfeiting,and integrated optical devices.

关键词： Polarization upconversion luminescence Degree of polarization Population density of excited state Number of upconversion photons Polarization anti-counterfeiting display

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Accurate Distinction of Weak and Strong AC Grids for Emerging Hierarchical-Infeed LCC-UHVDC Systems

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 772-777页

作者： Hao Xiao Xianzhong Duan yi zhang Department of Electrical and Computer Engineering University of ManitobaWinnipeg R3T 2N2ManitobaCanada State Key Laboratory of Advanced Electromagnetic Engineering and Technology Hubei Electric Power Security and High Efficiency Key LaboratorySchool of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074HubeiChina RTDS Technologies Inc. Winnipeg R3T 2E1ManitobaCanada

Distinction of weak and strong AC grids for emerging hierarchical-infeed LCC-UHVDC systems is important for planning and operation departments. However, accuracy of earlier distinction methods is limited as they were developed by empirical reasoning without rigorous theoretical analysis. Hence in this letter, hierarchical-infeed interactive effective short-circuit ratio (HIESCR) index is first used for strength evaluation of HIDC systems with complex inter-inverter interactions considered. Boundary HIESCR (BHIESCR) is also introduced in the proposed distinction method of weak and strong AC grids. That is, weak (or strong) AC grids are, respectively, identified when HIESCR is less (or greater) than BHIESCR. Second, it is shown BHIESCR remains almost unchanged as 3.0 versus various system parameters and rated operation variables based on rigorous theoretical analysis. This salient feature makes the proposed method more accurate than earlier methods. Finally, the proposed method is validated by simulations based on the PSCAD/EMTDC program.

关键词： Hierarchical-Infeedinteractive effective short-circuit ratio hierarchical-infeed LCC-UHVDC systems inter-inverter interactions strong AC grids weak AC grids

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