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AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

Science China Life Sciences 2025年第1期68卷 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

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Numerical Study of Flow and Heat Transfer Characteristics of Shell-and-Tube Molten Salt Electric Heater with Circularly Perforated Baffles

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Journal of Thermal Science 2025年第1期34卷 24-33页

作者： LIN Yongjie ZHANG Cancan WU Yuting ZHANG Yi LU Yuanwei Key Laboratory of Heat Transfer and Energy Conversion National User-Side Energy Storage Innovation Research and Development CenterBeijing University of Technology

Numerical simulations of the flow and heat transfer characteristics of four shell-and-tube molten salt electric heaters with different perforation rates was ***-and-tube electric heaters have the same geometry and tube arrangement,and all of them use single segmental baffles,but there exist four different baffle openings（φ）,i.e.,0%,2.52%,4.06%,and 6.31%.The results indicated that the reasonable baffle opening could significantly reduce the shell-side pressure drop,effectively decreasing the shell-side flow dead zone *** can eliminate the local high-temperature phenomenon on the surface of electric heating tubes,but the heat transfer coefficient is slightly *** perforated schemes significantly reduce shell-side pressure drop compared to the baseline solution without open *** particular,the φ=6.31% scheme exhibits the optimal performance among all the schemes,with a maximum reduction of up to 50.50% in shell-side pressure drop relative to the unopened holes *** heat transfer coefficient is the highest for φ=0%,exhibiting a range of5.26% to 5.73%,5.14% to 5.99%,and 7.31% to 8.54% higher than φ=2.52%,4.06%,and 6.31%,respectively,within the calculated *** composite index h/（Δp）1/3was higher for all open-hole solutions than that for the unopened-hole *** best overall performance was for φ=6.31%,which improved the composite index by15.29% to 17.18% over the unopened-hole solution.

关键词： molten salt electric heater perforated baffles heat transfer

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Constructing Pr-doped CoOOH catalytic sites for efficient electrooxidation of 5-hydroxymethylfurfural

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Journal of Energy Chemistry 2025年第1期100卷 234-244页

作者： Botao Fan Hao Zhang Bang Gu Feng Qiu Qiue Cao Wenhao Fang School of Chemical Science and Technology Yunnan University National center for International Research on Photoelectric and Energy Materials School of Materials and Energy Yunnan University

Electrocatalytic conversion of renewable biomass is emerging as a promising route for sustainable chemical production;hence it urgently calls for developing efficient electrocatalysts with low potentials and high current ***,a Pr-doped Co（OH）2hexagonal sheet （Pr/Co=1/9,in mole） is synthesized by electrodeposition as highly performant catalyst for 5-hydroxymethylfurfural （HMF） oxidation reaction（HMFOR） to produce 2,5-furandicarboxylic acid （FDCA）.This novel and low-cost catalyst possesses a rather low onset potential of 1.05 V （***） and requires only 1.10 V （***） to reach a current density of 10 mA cm-2for HMFOR,significantly outperforming Co（OH）2benchmark (i.e.,210 mV higher to reach10 m A cm-2).The origin of Pr promotion effect as well as the evolution of CoOOH catalytic sites and HMFOR process has been deeply elucidated by physical characterizations,kinetic experiments,in situ electrochemical techniques,and theoretical *** unique Pr-ameliorated CoOOH active centers enable 100%conversion of HMF,99.6%selectivity of FDCA,and 99.7%Faraday efficiency,with a superior cycling durability toward *** can be one of the most outstanding results for Co-based HMFOR catalysts to date in the *** this work can help open up new horizons for constructing novel and efficient Co-based electrocatalysts by the utilization of lanthanide elements.

关键词： Bioconversion

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A versatile synthetic strategy towards rare earth based metal-organic frameworks

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Science China Chemistry 2025年

作者： Quan Shi Yun-Hao Xu Ming-Hui Chen Peng Zhao Wen-Bo Deng Ji Xiong Kai Guo Ya-Qing Feng Bao Zhang School of Chemical Engineering and Technology Tianjin University Tianjin Collaborative Innovation center of Chemical Science and Engineering Guangdong Laboratory Chemistry & Fine Chemical Industry Jieyang center

Rare earth metal-organic frameworks (RE-MOFs) have drawn wide attention owing to diverse network structures and various application ***,due to the unpredictable formation of the nodes,it is still challenging to design novel RE-MOFs.A novel versatile strategy was developed employing a RE-acetate complex (RE2(CH3COO)6·4H2O) as a precursor to construct RE-MOFs.2D RE-MOFs (RE-DBP) and 3D RE-MOFs (RE-TCPP) could be obtained by using dicarboxylic porphyrin ligands H2DBP and tetracarboxylic porphyrin ligands H2TCPP,*** RE-MOFs were further synthesized to verify the universality of the *** crystalline RE-MOFs could also be prepared at room temperature via the developed strategy,which could significantly promote large-scale preparation and practical application of *** proof of the concept,the performance of porphyrin-based RE-MOFs was investigated in the photocatalytic cycloaddition of CO2with *** the RE-DBP(Co) MOFs,Tb-DBP(Co) exhibited the best photocatalytic performance,which was also greater than that of the corresponding 3D MOF Tb-TCPP(Co) due to the optimal 2D structure and thus the accelerated photogenerated charge separation and transfer *** work not only provides a novel versatile strategy to design and develop RE-MOFs,but also proposes a promising approach for the potential bulk production of RE-MOFs at room temperature.

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Arctic sea-ice extent: No record minimum in 2023 or recent years

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 52-55页

作者： Ola M.Johannessen Tor I.Olaussen Nansen Scientific Society BergenNorway Nansen Environmental and Remote Sensing center BergenNorway

Arctic sea-ice extent reaches its minimum each year in September. On 11 September 2023 the minimum was 4.969 million square kilometers(***^(2)). This was not a record low, which occurred in 2012, when the minimum was 4.175 ***^(2), 0.794 ***^(2) less than the minimum in 2023. However, the ice extent had decreased by 0.432 ***^(2) compared with 2022. Nevertheless, the summer melting in 2023 was remarkably less than expected when considering the strong heat waves in the atmosphere and ocean, with record temperatures set around the world. In general, there is a high correlation between the long-term decrease in sea-ice extent and the increasing CO_(2) in the atmosphere, where the increase of CO_(2) in recent decades explains about 80% of the decrease in sea ice in September, while the remainder is caused by natural variability.

关键词： Sea ice Arctic Minimum ice Climate

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Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key Laboratory of Behavioral Neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key Laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

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Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.Thomas M.Brandon Westover Can Zhang Department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA Division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(AD) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of AD is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van Dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

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Computational protein design and structure prediction—the 2024Nobel prize in chemistry

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Science China Chemistry 2025年

作者： Peilong Lu Lei Liu School of Life Sciences and Research center for Industries of the Future Westlake University Tsinghua-Peking Joint center for Life Sciences Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology Center for Synthetic and Systems Biology Department of Chemistry Tsinghua University

The 2024 Nobel prize in chemistry recognizes groundbreaking advancements in protein science, highlighting the power of artificial intelligence (AI) to decipher and design the molecular machinery of life. Half of the prize was awarded to David Baker for the computational design of proteins; the other to Demis Hassabis and John Jumper for their AI-driven predictions of protein structures. This article briefly reviews their achievements, and discusses the opportunities and directions that their work has enabled (Figure1).

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Software-defined process-near-memory architecture using 3D hybrid bonding integration

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Science China(Information Sciences) 2025年第1期68卷 366-378页

作者： Anlin XU Chenchen DENG Jianfeng ZHU Yao WANG Shaojun WEI Leibo LIU School of Integrated Circuits Tsinghua University Beijing Institution of Tracking and Communication Technology Beijing National Research center for Information Science and Technology Tsinghua University

With the unprecedented explosive growing amount of global data, the development of computing chips, which encounter bottlenecks such as power wall and memory wall, cannot satisfy the demanding requirement. This work proposes a software-defined process-near-memory(SDPNM) computing architecture implemented using 3D hybrid bonding *** software-defined chip architecture, featuring spatial computations and dynamic reconfiguration, innovates in a top-down manner to achieve high energy efficiency while maintaining flexibility after fabrication. The process-near-memory integration further advances the SDNPM chip in a bottom-up way to reduce the energy consumption of data movement while improving the bandwidth. Utilizing a relatively mature fabrication and bonding process can result in feasible solutions for both data-intensive and compute-intensive applications including digital signal processing and artificial intelligence. The logic die is fabricated in the SMIC 40 nm process and the DRAM die is fabricated in the PSMC 25 nm process. The hybrid bonding is implemented by XMC. The experimental results show that the energy efficiency of the proposed SDPNM chip is 33.1× better than the state-of-the-art FPGA ranging from 8.2× to 104.1×.

关键词： software-defined chips process near memory energy efficiency dynamic reconfiguration domain specific

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Lactate is a potentially harmful substitute for brain glucose fuel:consequences for metabolic restoration of neurotransmission

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Neural Regeneration Research 2025年第5期20卷 1403-1404页

作者： Oliver Kann Lennart Soder Babak Khodaie Institute of Physiology and Pathophysiology Heidelberg UniversityHeidelbergGermany Interdisciplinary center for Neurosciences(IZN) Heidelberg UniversityHeidelbergGermany

The metabolite lactate (L-lactate) can be generated and released by diverse brain cells,including neurons,astrocytes,and oligodendrocytes (Kann,2023;Rae et al.,2024).Lactate production usually requires the degradation of glucose (D-glucose)-and glycogen in astrocytes-to pyruvate by glycolysis and subsequent conversion of pyruvate to lactate by the enzyme lactate dehydrogenase(Figure 1A;Dienel,2019;Rae et al.,2024).

关键词： consequences Figure restoration

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