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Development of pharmacological immunoregulatory anticancer therapeutics:current mechanistic studies and clinical opportunities

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2477-2526页

作者： Nanhao Yin Xintong Li Xuanwei z.ang Shaolong xue Yu Cao Gabriele Niedermann You Lu Jianxin xue Division of Thoracic Tumor Multimodality Treatment Cancer Center&State Key Laboratory of Biotherapyand The National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.37Guoxue LaneChengdu 610041 SichuanPR China Department of Gynecology and Obstetrics West China Second University HospitalSichuan UniversityNo.20Section 3South Renmin RoadChengdu 610041 SichuanPR China Department of Emergency Medicine Laboratory of Emergency MedicineWest China HospitalSichuan UniversityNo.37Guoxue LaneChengdu 610041 SichuanPR China Institute of Disaster Medicine&Institute of Emergency Medicine Sichuan UniversityNo.17Gaopeng AvenueChengdu 610041 SichuanPR China Department of Radiation Oncology Medical Center—University of FreiburgFaculty of MedicineUniversity of FreiburgGerman Cancer Consortium(DKTK)Partner Site DKTK-FreiburgRobert-Koch-Strasse 379106 FreiburgGermany Laboratory of Clinical Cell Therapy West China HospitalSichuan UniversityNo.2222Xinchuan RoadChengdu 610041 SichuanPR China

Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment,but challenges related to resistance and toxicity still *** to the advancement of immuno-oncology,an increasing number of novel immunoregulatory targets and mechanisms are being revealed,with relevant therapies promising to improve clinical immunotherapy in the foreseeable ***,comprehending the larger picture is *** this review,we analyze and summarize the current landscape of preclinical and translational mechanistic research,drug development,and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint *** with further clarification of cancer immunobiology and advances in antibody engineering,agents targeting additional inhibitory immune checkpoints,including LAG-3,TIM-3,TIGIT,CD47,and B7 family members are becoming an important part of cancer immunotherapy research and discovery,as are structurally and functionally optimized novel anti-PD-(L)1 and anti-CTLA-4 agents and agonists of co-stimulatory molecules of T *** by bispecific T cell engagers,newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical ***-generation agents also include immune epigenetic drugs and cytokine-based *** therapies,cancer vaccines,and oncolytic viruses are not covered in this *** comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.

关键词： clinical immuno landscape

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A stable implicit nodal integration-based particle finite element method(N-PFEM)for modelling saturated soil dynamics

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第6期16卷 2172-2183页

作者： Liang Wang xue z.ang Jingjing Meng Qinghua Lei Department of Earth Sciences ETH ZürichZürich8092Switzerland Department of Civil Engineering and Industrial Design University of LiverpoolLiverpoolL693BXUK Department of Civil Environmental and Natural Resources EngineeringLuleåUniversity of TechnologyLuleå97187Sweden Department of Earth Sciences Uppsala UniversityUppsala75105Sweden

In this study,we present a novel nodal integration-based particle finite element method(N-PFEM)designed for the dynamic analysis of saturated *** approach incorporates the nodal integration technique into a generalised Hellinger-Reissner(HR)variational principle,creating an implicit PFEM *** mitigate the volumetric locking issue in low-order elements,we employ a node-based strain smoothing *** discretising field variables at the centre of smoothing cells,we achieve nodal integration over cells,eliminating the need for sophisticated mapping operations after re-meshing in the *** express the discretised governing equations as a min-max optimisation problem,which is further reformulated as a standard second-order cone programming(SOCP)***,pore water pressure,and displacements are simultaneously determined using the advanced primal-dual interior point ***,our numerical model offers improved accuracy for stresses and pore water pressure compared to the displacement-based PFEM *** experiments demonstrate that the N-PFEM efficiently captures both transient and long-term hydro-mechanical behaviour of saturated soils with high accuracy,obviating the need for stabilisation or regularisation techniques commonly employed in other nodal integration-based PFEM *** work holds significant implications for the development of robust and accurate numerical tools for studying saturated soil dynamics.

关键词： Particle finite element method Nodal integration Dynamic saturated media Second-order cone programming(SOCP)

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Effects of longitudinal magnetic field on primary dendrite spacing and segregation of directionally solidified single crystal superalloy

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Progress in Natural Science:Materials International 2024年第1期34卷 26-36页

作者： Congjiang z.ang Yilin zhou Chen Shen Weili Ren Xiaotan Yuan Biao Ding Haibiao Lu zuosheng Lei Yunbo zhong ang z.ang State Key Laboratory of Advanced Special Steel College of Materials Science and Engineering Shanghai University National Engineering Research Center for Magnesium Alloys Natural Key Laboratory of Advanced Casting Technologies College of Materials Science and EngineeringChongqing University

The primary dendrite spacing(PDS) and segregation of directionally solidified single crystal(SC) superalloy under the longitudinal magnetic field(LMF) were investigated based on the analysis of the whole cross-sectional microstructure at different solidification distances. The results show that the PDS under the LMF remains basically unchanged at different solidification distances, and it is greater than that under no LMF. With the increase of magnetic field intensity, the PDS increases and the macrosegregation decreases. The increasing PDS and reducing segregation under the LMF can be attributed to the increase of solute boundary layer, which expands the non-equilibrium freezing temperature range and brings the effective partition coefficient closer to 1. The increase of the solute enrichment layer thickness could be caused by the downward secondary circulation generated by the thermoelectric magnetic convection(TEMC) near the interface, which drives the migration of solutes towards the interdendritic region. This work not only clarifies the mechanism of LMF controlling PDS and reducing segregation by TEMC, but also provides theoretical guidance for producing high-quality SC superalloys using magnetic fields.

关键词： Primary dendrite spacing Segregation Single crystal superalloy Directional solidification Magnetic field Thermoelectric magnetic convection

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Boosting ammonia production in electrocatalytic NO_(x)reduction on a robust Fe/FeMoO_(4)catalyst

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Nano Research 2024年第7期17卷 5801-5806页

作者： Dong-xue Liu Xin Deng Yong-Fu zhu zhe Meng xue-Feng Sun Miao-Miao Shi Hai-Xia zhong Jun-Min Yan Key Laboratory of Automobile Materials Ministry of EducationSchool of Materials Science and EngineeringJilin UniversityChangchun 130022China State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China

Electrocatalytic reduction of nitrate(NO_(3)^(−))and nitride(NO_(2)^(−))to ammonia(NH3)is of wide interest as a promising alternative to the energy-intensive Haber-Bosch route for mitigating the vast energy consumption and the accompanied carbon dioxide emission,as well as benefiting for the relevant sewage ***,exploring an efficient and low-cost catalyst with high atomic utilization that can effectively facilitate the slow multi-electron transfer process remains a grand ***,we present an efficient hydrogenation of NO_(3)^(−)/NO_(2)^(−)species to NH3 in both alkaline and neutral environments over the Fe_(2)(MoO_(4))_(3)derived hybrid electrocatalyst with the metallic Fe site on FeMoO_(4)(Fe/FeMoO_(4)).The Mo ingredient can play a synergistically positive role in further promoting the NH_(3) production on *** a result,Fe/FeMoO_(4)behaves well in the electrochemical NH_(3) generation from NO_(2)^(−)with a maximum NH_(3) Faradaic efficiency(FE)of 96.53%and 87.68%in alkaline and neutral electrolyte,corresponding to the NH_(3) yield rate of 640.68 and 302.56 mg·h^(−1)·mg_(cat.)^(−1),respectively,which outperforms the Fe and Mo counterpart and other similar catalyst,showing the robust catalytic capacity of each active site.

关键词： ammonia synthesis NO_(x)reduction synergistic effect alkaline/neutral electrolyte

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T1 colorectal cancer management in the era of minimally invasive endoscopic resection

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2284-2294页

作者： Shirley xue Jiang Aein zarrin Neal Shahidi Department of Medicine University of British ColumbiaVancouver V6Z2K5British ColumbiaCanada Division of Gastroenterology St.Paul’s HospitalVancouver V6Z2K5British ColumbiaCanada

T1 colorectal cancer(CRC),defined by tumor invasion confined to the submucosa,has historically been managed by *** understanding of recurrence and lymph node metastases risk,coupled with advances in endoscopic resection techniques,have led to an increasing capacity for organ-sparing local *** invasive management of T1 CRC begins with optical evaluation of the lesion to diagnose invasive disease and quantify depth of invasion,which informs therapeutic decision *** selection between various available endoscopic resection techniques depends upon lesion characteristics,technique risk-benefit profiles,and location-specific *** endoscopic resection,established histopathology features determine the risk of recurrence and subsequent management including surveillance or adjuvant surgical *** management of non-operative candidates deviates from conventional recommendations with emerging treatment strategies in select populations.

关键词： Cancer Colonoscopy Endoscopy Polyp Surgery

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Experimental study on seismic reinforcement of bridge foundation on silty clay landslide with inclined interlayer

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Earthquake Engineering and Engineering Vibration 2024年第1期23卷 193-207页

作者： Lei Da Xiao Hanmo Ran Jianhua Luo Bin Jiang Guanlu xue Tianlang College of Civil Engineering Sichuan Agricultural UniversityDujiangyan 611830China Sichuan Higher Education Engineering Research Center for Disaster Prevention and Mitigation of Village Construction Dujiangyan 611830China School of Civil Engineering Southwest Jiaotong UniversityChengdu 610031China

A shaking table test for a bridge foundation reinforced by anti-slide piles on a silty clay landslide model with an inclined interlayer was *** deformation characteristics of the bridge foundation piles and anti-slide piles were analyzed in different loading *** dynamic response law of a silty clay landslide with an inclined interlayer was *** spacing between the rear anti-slide piles and bridge foundation should be reasonably controlled according to the seismic fortification requirements,to avoid the two peaks in the forced deformation of the bridge foundation ***“blocking effect”of the bridge foundation piles reduced the deformation of the forward anti-slide *** stress-strain response of silty clay was intensified as the vibration wave field appeared on the *** the vibration intensified,the thrust distribution of the landslide underwent a process of shifting from triangle to inverted trapezoid,the difference in the acceleration response between the bearing platform and silty clay landslide tended to decrease,and the spectrum amplitude near the natural vibration frequency *** rear anti-slide piles were able to slow down the shear deformation of the soil in front of the piles and avoid excessive acceleration response of the bridge foundation piles.

关键词： silty clay landslide inclined interlayer shaking table test anti-slide pile bridge foundation pile

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Research on ozone formation sensitivity based on observational methods:Development history,methodology,and application and prospects in China

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Journal of Environmental Sciences 2024年第4期138卷 543-560页

作者： Wanghui Chu Hong Li Yuanyuan Ji Xin z.ang Likun xue Jian Gao Cong An State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China Environment Research Institute Shandong UniversityQingdao 266237China

Observation-based method for O_(3)formation sensitivity research is an important tool to analyze the causes of ground-level O_(3)pollution,which has broad application potentials in determining the O_(3)pollution formation mechanism and developing prevention and control *** paper outlined the development history of research on O_(3)formation sensitivity based on observational methods,described the principle and applicability of the methodology,summarized the relative application results in China and provided recommendations on the prevention and control of O_(3)pollution in China based on relevant study results,and finally pointed out the shortcomings and future development prospects in this field in *** overview study showed that the O_(3)formation sensitivity in some urban areas in China in recent years presented a gradual shifting tendency from the VOC-limited regime to the transition regime or the NO_(x)-limited regime due to the implementation of the O_(3)precursors emission reduction policies;O_(3)pollution control strategies and precursor control countermeasures should be formulated based on local conditions and the dynamic control capability of O_(3)pollution control measures should be *** are still some current deficiencies in the study field in ***,it is recommended that a stereoscopic monitoring network for atmospheric photochemical components should be further constructed and improved;the atmospheric chemical mechanisms should be vigorously developed,and standardized methods for determining the O_(3)formation sensitivity should be established in China in the near future.

关键词： Observation-based method Ozone formation sensitivity Ozone pollution prevention and control VOCs NO_(x) OBM

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Reconcile the contradictory wettability requirements for the reduction and oxidation half-reactions in overall CO_(2) photoreduction via alternately hydrophobic surfaces

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Journal of Energy Chemistry 2024年第6期93卷 202-212,I0006页

作者： Hailing Huo Ting Hu Chengxi Huang Fang Wu Tongyu Wang Xuan Liu Liang z.ang Qiang Ju zhiqing zhong Hongbin Xing Erjun Kan ang Li MIIT Key Laboratory of Semiconductor Microstructure and Quantum Sensing Nanjing University of Science and TechnologyNanjing 210094JiangsuChina College of Information Science and Technology Nanjing Forestry UniversityNanjing 210037JiangsuChina

The overall photocatalytic CO_(2) reduction reaction(OPCRR)that can directly convert CO_(2) and H_(2)O into fuels represents a promising renewable energy conversion *** a typical redox reaction,the OPCRR involves two half-reactions:the CO_(2) reduction half-reaction(CRHR)and the water oxidation half-reaction(WOHR).Generally,both half-reactions can be promoted by adjusting the wettability of ***,there is a contradiction in wettability requirements for the two ***,CRHR prefers a hydrophobic surface that can accumulate more CO_(2) molecules on the active sites,ensuring the appropriate ratio of gas-phase(CO_(2))to liquid-phase(H_(2)O)***,the WOHR prefers a hydrophilic surface that can promote the departure of the gaseous product(O_(2))from the catalyst surface,preventing isolation between active sites and the reactant(H_(2)O).Here,we successfully reconciled the contradictory wettability requirements for the CRHR and WOHR by creating an alternately hydrophobic *** was achieved through a selectively hydrophobic modification method and a charge-transfer-control ***,the collaboratively promoted CRHR and WOHR led to a significantly enhanced OPCRR with a solar-to-fuel conversion efficiency of 0.186%.Notably,in ethanol production,the catalyst exhibited a 10.64-fold increase in generation rate(271.44μmol g^(-1)h~(-1))and a 4-fold increase in selectivity(55.77%)compared to the benchmark *** innovative approach holds great potential for application in universal overall reactions involving gas participation.

关键词： Hydrophobic Hydrophilic Gas transport Overall CO_(2)photoreduction z-scheme

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不同NaOH预处理浓度和预处理时间对麦秆常温厌氧发酵效率的影响

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安全与环境学报 2024年第1期24卷 271-279页

作者：张鸣李昂李雪米璇兰州城市学院城市环境学院兰州730070

在确保NaOH对小麦秸秆预处理效果的前提下,通过适当延长预处理时间可减少NaOH用量,进而降低二次污染风险,为小麦秸秆的户用沼气生产提供理论依据。采用自行设计的厌氧发酵装置,研究不同NaOH预处理质量分数和预处理时间对小麦秸秆常温(20... 详细信息

在确保NaOH对小麦秸秆预处理效果的前提下,通过适当延长预处理时间可减少NaOH用量,进而降低二次污染风险,为小麦秸秆的户用沼气生产提供理论依据。采用自行设计的厌氧发酵装置,研究不同NaOH预处理质量分数和预处理时间对小麦秸秆常温(20℃)厌氧发酵效率的影响。结果显示,在小麦秸秆常温厌氧发酵时,NaOH质量分数为3%时的预处理效果优于质量分数为0和6%的预处理效果;在预处理7~28 d时,纤维素、半纤维素和木质素的脱除率分别为3.66%~8.07%、43.08%~46.43%和47.88%~51.44%;发酵时的初始pH值为8.36~8.47,108~113 d发酵基本完成,累积产甲烷1 565.80~1 833.16 mL,干物质累积产甲烷体积为97.86~114.57 mL/g,产甲烷速率为13.86~16.97 mL/d,甲烷体积分数为50%~58%的持续时间为57~72 d。通过响应面模型试验得到最优预处理条件为:NaOH质量分数为4.36%,预处理时间为12.44 d。该条件下干物质甲烷产量的实测值为113.76 mL/g,与预测值接近,相对误差小于5%,表明模型有效。综合判断,在小麦秸秆常温(20℃)厌氧发酵时,利用质量分数为4.36%(以秸秆干重计)的NaOH对秸秆进行预处理切实可行。

关键词：环境工程学小麦秸秆厌氧发酵 NaOH 预处理累积产甲烷体积响应面

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双层单原子催化剂用于促进高活性和选择性电催化硝酸盐还原制氨

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物理化学学报 2024年第6期40卷 60-62页

作者：于镜坤雍雪曹昂卢思宇郑州大学化学学院绿色催化中心郑州450001 Department of Chemistry University of SheffieldSheffieldS37HFUK Department of Physics Technical University of DenmarkKongens Lyngby 2800Denmar

高效、高选择性的单原子催化剂(SACs)在电催化硝酸盐还原制氨过程中具有重要作用。然而,由于中间体、金属活性中心和配位环境之间复杂的竞争性电子相互作用,仍然面临挑战。本研究采用密度泛函理论(DFT)计算,对27种SACs以及双层SACs(BSA... 详细信息

高效、高选择性的单原子催化剂(SACs)在电催化硝酸盐还原制氨过程中具有重要作用。然而,由于中间体、金属活性中心和配位环境之间复杂的竞争性电子相互作用,仍然面临挑战。本研究采用密度泛函理论(DFT)计算,对27种SACs以及双层SACs(BSACs)进行了系统研究,通过轴向d-d轨道杂化提高了从SACs到BSACs的电催化硝酸盐还原反应(NO_(3)RR)的活性和选择性。考虑到可能的O端、N端、NO端和NO二聚体途径,计算结果显示,在单层SACs中,Ti-Pc和V-Pc分别具有优异的极限电位(U_(L)),分别为-0.24和-0.48V。形成能、溶解势以及从头算分子动力学结果表明,在反应条件下,这些催化剂非常稳定。在这些单层TM-Pc中,它们的d带能级和占据数受到d_(xz)/d^(yz)和p_(z)轨道杂化的影响。其轴向d_(z^(2))轨道的可用性通过形成d_(z^(2))-d_(z^(2))相互作用来进一步调整d带和反应性。在此基础上,以Ti-Pc和V-Pc为底物,通过形成轴向d-d轨道杂化来构建BSACs,为调节NO_(3)RR催化性能提供了一种独特的新途径。重要的是,我们发现d带中心(εd)、d_(xz)+d_(yz)轨道的占据数和U_(L)之间存在二维火山关系,用于描述它们的NO_(3)RR催化性能。最佳的BSACs应该同时具备适当的ε_(d)和d_(xz)+d_(yz)占用数。Ti-Mo和Ti-Ta被确定为出色的NO_(3)RR催化剂,其U_(L)均降低至-0.13 V。而d_(z^(2))-d_(z^(2))轨道之间的杂化则增强了双层金属之间的电荷转移和结构稳定性。缺乏相邻的金属位点将导致生成NO_(2)、NO和N_(2)的能垒较高,从而抑制副产物生成。最终,本研究揭示了在SACs和BSACs上对硝酸盐还原进行合理优化的方法,可为改进电催化剂的设计提供指导。

关键词：硝酸盐还原第一性原理计算单原子催化剂双层单原子催化剂轴向轨道杂化

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