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Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1742-1758页

作者： Renming Fan Ruizhuo Lin Shuo zhang Aohua Deng Yongrui hai Junyan Zhuang Yang Liu Maosheng Cheng Gaofei wei Institute of Medical Research Northwestern Polytechnical UniversityXi'an 710072China Research&Development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518057China Key Laboratory of Structure-Based Drug Design and Discovery Ministry of EducationSchool of Pharmaceutical EngineeringShenyang Pharmaceutical UniversityShenyang 110016China

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to the activation of cellular oxidative stress and immune responses. While the role of mitochondrial membrane remodeling in promoting inflammation in hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which is composed of oxaliplatin (Oxa) and acetaminophen (APAP), to enhance its anti-tumor effects and amplify the immune response. Our findings demonstrate that OAP2 induces nuclear DNA damage, resulting in the production of nuclear DNA. Additionally, OAP2 downregulates the expression of mitochondrial Sam50, to promote mitochondrial membrane remodeling and trigger mtDNA secretion, leading to double-stranded DNA accumulation and ultimately synergistically activating the intracellular cGAS-STING pathway. The mitochondrial membrane remodeling induced by OAP2 overcomes the limitations of Oxa in activating the STING pathway and simultaneously promotes gasdermin-D-mediated cell pyroptosis. OAP2 also promotes dendritic cell maturation and enhances the quantity and efficacy of cytotoxic T cells, thereby inhibiting cancer cell proliferation and metastasis. Briefly, our study introduces the first novel small-molecule inhibitor that regulates mitochondrial membrane remodeling for active immunotherapy in anti-tumor research, which may provide a creative idea for targeting organelle in anti-tumor therapy.

关键词： Anti-tumor drug Prodrug Platinum Chemo-immunotherapy Mitochondrial membrane modeling STING Pyroptosis mtDNA

The role of vitamin E in polyunsaturated fatty acid synthesis and alleviating endoplasmic reticulum stress in sub-adult grass carp(Ctenopharyngodon idella)

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Animal Nutrition 2024年第1期16卷 275-287页

作者： Ke Yao Lin Feng wei-Dan Jiang Yang Liu Lu zhang hai-Feng Mi Xiao-Qiu Zhou Pei Wu Animal Nutrition Institute Sichuan Agricultural University Fish Nutrition and Safety Production University Key Laboratory of Sichuan Province Sichuan Agricultural University Key Laboratory of Animal Disease-Resistance Nutrition Ministry of Education Ministry of Agriculture and Rural Affairs Key Laboratory of Sichuan Province Tongwei Co. Ltd. Healthy Aquaculture Key Laboratory of Sichuan Province

Vitamin E(VE) is an essential lipid-soluble vitamin that improves the fish flesh quality. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of VE on growth performance and flesh quality in sub-adult grass carp(Ctenopharyngodon idella). A total of 450fish(713.53 ± 1.50 g) were randomly divided into six treatment groups(three replicates per treatment)and fed for nine weeks with different experimental diets(dietary lipid 47.8 g/kg) that contained different levels of VE(5.44, 52.07, 96.85, 141.71, 185.66, and 230.12 mg/kg diet, supplemented as dl-a-tocopherol acetate). Notably, the treatment groups that were fed with dietary VE ranging from 52.07 to230.12 mg/kg diet showed improvement in the percent weight gain, special growth rate, and feed efficiency of grass carp. Moreover, the treatment groups supplemented with dietary VE level of 141.71,185.66, and 230.12 mg/kg diet showed enhancement in crude protein, lipid, and a-tocopherol contents in the muscle, and the dietary levels of VE ranging from 52.07 to 141.71 mg/kg diet improved muscle pH24h and shear force but reduced muscle cooking loss in grass carp. Furthermore, appropriate levels of VE(52.07 to 96.85 mg/kg diet) increased the muscle polyunsaturated fatty acid content in grass carp. Dietary VE also increased the mRNA levels of fatty acid synthesis-related genes, including fas, scd-1, fad,elovl, srebp1, pparγ, and lxra, and up-regulated the expression of SREBP-1 protein. However, dietary VE decreased the expression of fatty acid decomposition-related genes, including hsl, cpt1, acox1, and ppara,and endoplasmic reticulum stress-related genes, including perk, ire1, atf6, eif2a, atf4, xbp1, chop, and grp78, and down-regulated the expression of p-PERK, p-IRE1, ATF6, and GRP78 proteins. In conclusion,dietary VE increased muscle fatty acid synthesis, which may be partly associated with the alleviation of endoplasmic reticulum stress, and ultimately improves fish fles

关键词： Vitamin E Flesh quality Muscle polyunsaturated fatty acid level Endoplasmic reticulum stress Growth performance Grass carp

Accelerating Asteroidal Period and Pole Inversion from Multiple Lightcurves Using Parallel Differential Evolution and Cellinoid Shape Model

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Research in Astronomy and Astrophysics 2024年第4期24卷 271-286页

作者： Yong-Xiong zhang Wen-Xiu Guo Xiao-Ping Lu Hua Zheng hai-Bin Zhao Jun Tian wei-Lin Wang School of Engineering Guangzhou College of Technology and BusinessGuangzhou 510850China School of Computer Science and Engineering Macao University of Science and TechnologyTaipaMacao 999078China School of Mathematics and Statistics Shaoguan UniversityShaoguan 512099China State Key Laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao 999078China Key Laboratory of Planetary Sciences Purple Mountain ObservatoryCASNanjing 210023China

Determining asteroid properties provides valuable physical insights but inverting them from photometric lightcurves remains computationally *** paper presents a new approach that combines a simplified Cellinoid shape model with the Parallel Differential Evolution(PDE)algorithm to accelerate *** PDE algorithm is more efficient than the Differential Evolution algorithm,achieving an extraordinary speedup of 37.983 with 64 workers on multicore *** PDE algorithm accurately derives period and pole values from simulated *** analysis of real asteroid lightcurves validates the method’s reliability:in comparison with results published elsewhere,the PDE algorithm accurately recovers the rotational periods and,given adequate viewing geometries,closely matches the pole *** PDE approach converges to solutions within 20,000 iterations and under one hour,demonstrating its potential for large-scale data *** work provides a promising new tool for unveiling asteroid physical properties by overcoming key computational bottlenecks.

关键词： methods:numerical minor planets asteroids:general techniques:photometric astrom

Insight into vertical piezoelectric characteristics regulated thermal transport in van der Waals two-dimensional materials

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Rare Metals 2024年第2期43卷 770-779页

作者： Dong-hai wei E Zhou Jin-Yuan Xu Hui-Min Wang Chen Shen Hong-Bin zhang Zhen-Zhen Qin Guang-Zhao Qin State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body College of Mechanical and Vehicle EngineeringHunan UniversityChangsha410082China Hunan Key Laboratory for Micro-Nano Energy Materials and Device and School of Physics and Optoelectronics Xiangtan UniversityXiangtan411105China Institute of Materials Science Technical University of DarmstadtAlarich-Weiss-Str.264287DarmstadtGermany School of Physics and Microelectronics Zhengzhou UniversityZhengzhou450001China

The urgent demand of extreme(ultra-high/low)thermal conductivity materials is triggered by the high-power device,where exploring the theories and mechanisms of regulating thermal transport properties plays a key ***,we elaborately investigate the effect of vertical(out-of-plane)piezoelectric characteristics on thermal transport,which is historically *** different stacking-order(AA and AB)bilayer boron nitride(Bi-BN)in two-dimensional(2D)materials are selected as study *** performing state-of-the-art first-principles calculations,it is found that the polarization charge along the out-of-plane orientation ascends significantly with the increasing piezoelectric response in AB stacked Bi-BN(Bi-BN-AB)followed by the enhanced interlayer B–N atomic ***,the amplitude of phonon anharmonicity in Bi-BN-AB increases larger than that in the AA stacked Bi-BN(Bi-BN-AA),resulting in the dramatic weakening of the thermal conductivity by 20.34%under 18%*** research reveals the significant role of the vertical(out-of-plane)piezoelectric characteristic in regulating thermal transport and provides new insight into accurately exploring the thermal transport performance of 2D van der Waals materials.

关键词： Thermal conductivity Piezoelectric effect 2D materials Bilayer BN Strain engineering

From Liquid to Solid‑State Lithium Metal Batteries:Fundamental Issues and Recent Developments

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Nano-Micro Letters 2024年第2期16卷 68-125页

作者： Zhao zhang wei‑Qiang Han School of Materials Science and Engineering Zhejiang UniversityHangzhou 310027People’s Republic of China

The widespread adoption of lithium-ion batteries has been driven by the proliferation of portable electronic devices and electric vehicles,which have increasingly stringent energy density *** metal batteries(LMBs),with their ultralow reduction potential and high theoretical capacity,are widely regarded as the most promising technical pathway for achieving high energy density *** this review,we provide a comprehensive overview of fundamental issues related to high reactivity and migrated interfaces in ***,we propose improved strategies involving interface engineering,3D current collector design,electrolyte optimization,separator modification,application of alloyed anodes,and external field regulation to address these *** utilization of solid-state electrolytes can significantly enhance the safety of LMBs and represents the only viable approach for advancing *** review also encompasses the variation in fundamental issues and design strategies for the transition from liquid to solid *** noteworthy is that the introduction of SSEs will exacerbate differences in electrochemical and mechanical properties at the interface,leading to increased interface inhomogeneity—a critical factor contributing to failure in all-solidstate lithium metal *** on recent research works,this perspective highlights the current status of research on developing high-performance LMBs.

关键词： Lithium metal batteries All-solid-state lithium metal battery Li dendrite Solid electrolyte Interface

Possibilities for the synthesis of superheavy element Z=121 in fusion reactions

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Nuclear Science and Techniques 2024年第6期35卷 90-100页

作者： Ming-Hao zhang Yu-hai zhang Ying Zou Xiu-Xiu Yang Gen zhang Feng-Shou zhang The Key Laboratory of Beam Technology of Ministry of Education College of Nuclear Science and TechnologyBeijing Normal UniversityBeijing 100875China Institute of Radiation Technology Beijing Academy of Science and TechnologyBeijing 100875China School of Physical Science and Technology Guangxi UniversityNanning 530004China National Laboratory of Heavy Ion Accelerator of Lanzhou Center of Theoretical Nuclear PhysicsLanzhou 730000China

Based on the dinuclear system model,the calculated evaporation residue cross sections matched well with the current experimental *** synthesis of superheavy elements Z=121 was systematically studied through combinations of stable projectiles with Z=21-30 and targets with half-lives exceeding 50 *** influence of mass asymmetry and isotopic dependence on the projectile and target nuclei was investigated in *** reactions^(254)Es(^(46)Ti,3n)^(297)121 and^(252)Es(^(46)Ti,3n)^(295)121 were found to be experimentally feasible for synthesizing superheavy element Z=121,with maximal evaporation residue cross sections of 6.619 and 4.123 fb at 219.9 and 223.9 MeV,respectively.

关键词： Superheavy nuclei Dinuclear system model Fusion reaction Evaporation residue cross section

State of the art of lightweight aggregates used in lightweight refractories for working lining of high-temperature furnaces

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Journal of Iron and Steel Research(International) 2024年第6期31卷 1320-1343页

作者： wei zhang Wen-yong Dai Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016LiaoningChina Research and Development Department AGC Plibrico(Dalian)Industries Inc.Dalian 116600LiaoningChina

Lightweight refractories for the working lining of high-temperature furnaces play an important role in the smelting of advanced steels and *** prepare lightweight refractories for the working lining of high-temperature furnaces,the synthesis of lightweight aggregates is the ***,the research on the synthesis of lightweight aggregates with high service temperature,low thermal conductivity,high strength,and good slag resistance has received widespread *** available literature on the synthesis of lightweight aggregates was summarized,including corundum,mullite,mullite-corundum,spinel,corundum-spinel,cordierite,cordierite-mullite,calcium hexaluminate,corundum-calcium hexaluminate,bauxite,magnesia,magnesia-based,and forsterite-based ***,the future development trend of lightweight aggregates was proposed.

关键词： Lightweight aggregate Lightweight refractory Working lining Apparent porosity Closed porosity Thermal conductivity Pore-forming approach

Humic acid-mediated transport of a typical soil passivation remediation product(chloropyromorphite)in saturated porous media

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Journal of Environmental Sciences 2024年第7期141卷 51-62页

作者： Xinying Li Mengjia zhang Siyuan Li wei wei School of Environment Jiangsu Engineering Lab of Water and Soil Eco-remediationJiangsu Province Engineering Research Center of Environmental Risk Prevention and Emergency Response TechnologyNanjing Normal UniversityNanjing 210023China Jiangsu Center for Collaborative Innovation in Geographical Information Resource Development and Application Nanjing 210023China

Conversion of labile Pb species into chloropyromorphite(CPY)using phosphorus-bearing amendments was considered to be an ideal strategy in soil passivation ***,the fate and transport of CPY in the soil are poorly *** study aims to fill the knowledge gap by evaluating the fate and transport of CPY under environmentally relevant conditions of humic acid(HA),pH,electrolyte concentration,and species through the saturated sandy *** showed that bare CPY colloids are basically immobile in sandy porous media while the co-existence of HA made the transport of CPY improved by30%-93.5%.Facilitated transport of CPY was attributed to the increased stability of CPY and the repulsive interaction between CPY particles and sands due to HA *** mobility of CPY was also increased with increasing pH from 5.0 to *** the pH was 9 with a10 mmol/L NaCl background solution,the stronger energy barrier between CPY and sand led to enhanced transport *** divalent Ca^(2+)had a more dramatic effect than monovalent Na^(+)on the aggregation and sedimentation of CPY colloids due to its effectivescreening of the surface charge of CPY and bridging interaction with CPY ***-LandauVerwey-Overbeek theory and attachment efficiency calculation indicated that high energy barriers were responsible for the high mobility of CPY colloids,while the retention of CPY in sands was mainly caused by secondary energy minimum and physically *** findings of this work can help to evaluate the fate of soil passivation remediation products in natural water and soil.

关键词： Chloropyromorphite DLVO theory Stability Saturated porous medium Transport

Data-driven mapping-relationship mining between hardness and mechanical properties of dual-phase titanium alloys via random forest and statistical analysis

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Rare Metals 2024年第2期43卷 829-841页

作者： hai-Chao Gong Qun-Bo Fan Hong-Mei zhang Xing-Wang Cheng Wen-Qiang Xie Kai Chen Lin Yang Jun-Jie zhang Bing-Qiang wei Shun Xu School of Materials Science and Engineering Beijing Institute of TechnologyBeijing100081China National Key Laboratory of Science and Technology on Materials Under Shock and Impact Beijing100081China Beijing Institute of Technology Chongqing Innovation Center Chongqing401135China Department of Mechanical and Materials Engineering University of Nebraska-LincolnLincolnNE68588USA

In order to accelerate the research on the property optimization of titanium alloy based on high-throughput methods,it is necessary to reveal the relationship between hardness and other mechanical properties which is still *** this work,taking Ti20C alloy as research object,almost all the microstructure of dual-phase titanium alloys were covered by traversing over 100 heat treatment ***,massive experiments including microstructure characterization and performance test were conducted,obtaining 51,590 pieces of microstructure data and 3591 pieces of mechanical property ***,based on large-scale data-driven technology,the quantitative mapping relationship between hardness and other mechanical properties was deeply *** results of random forest models showed that the correlation between hardness(H)and Charpy impact energy(A_(k))(or elongation,A)was hardly dependent on the microstructure types,while the relationship between H and tensile strength(R_(m))(or yield strength,R_(p0.2))was highly dependent on microstructure ***,combined with statistical analysis,it was found that the relationship between H and Ak(or A)were negatively ***,the relationship between H and strength was positively linear for equiaxed microstructure,and strength was linked to d^(−1/2)(d,equivalent circle diameter)ofα-grains in the form of classical Hall–Petch formula;but for other microstructures,the relationships were ***,the above rules were nearly the same in the rolling direction and transverse ***,a"four-quadrant partition map"between H and R_(p0.2)/R_(m) was established as a versatile material-screening tool,which can provide guidance for on-demand selection of titanium alloys.

关键词： Dual-phase titanium alloy Data-driven Hardness Mapping relationship