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26篇 您的检索式:作者名="Siwei Lin"
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1Incidence and mortality of primary bone cancers in China, 2014显示文摘Objective: In this study, we aimed to estimate the updated incidence and mortality of primary bone cancers based on population-based cancer registration data in 2014, collected by the National Central Cancer Registry of China(NCCRC).Methods: In 2017, 339 registries' data were qualified based on data quality criteria set down by the NCCRC.Cases of primary bone cancers were retrieved from the national database. We estimated numbers of primary bone cancer cases and deaths in China using age-specific rates and corresponding national population stratified by area,sex, age-group(0, 1-4, 5-9, 10-14, …, 85+). Chinese standard population in 2000 and Segi's World population were applied for the calculation of age-standardized incidence and mortality rates.Results: In 2014, 24,000 primary bone cancer cases and 17,200 deaths attributable to primary bone cancers were estimated to have occurred in China. The crude incidence rate of primary bone cancers was 1.76/100,000, with agestandardized incidence rate by Chinese standard population(ASIRC) and by World standard population(ASIRW)being 1.35/100,000 and 1.32/100,000, respectively. The crude mortality rate of primary bone cancers was1.26/100,000, with age-standardized mortality rate by Chinese standard population(ASMRC) and by World standard population(ASMRW) being 0.88/100,000 and 0.86/100,000, respectively. Age-specific incidence curve was bimodally distributed with age, with the first peak occurring in the second decade of the life and the second peak in the elderly. Males had higher crude and age-standardized rates for both incidence and mortality compared with females. Both crude and age-standardized incidence rates were higher in rural areas than in urban areas, so were the crude and age-standardized mortality rates.Conclusions: This population-based study presents the most recently available estimates on primary bone cancers in China, revealing that the males are 1.34 times as much as females suffering from primary bone cancers and the adolescents in puberty and the elderly are predominantly affected groups by these cancers. High-quality cancer registration data are a prerequisite for undertaking further study for gaining insight into the causes and risk factors for primary bone cancers in China.Liang Xia Rongshou Zheng Yanjun Xu Xiaojun Xu Siwei Zhang Hongmei Zeng Lifeng Lin Wanqing Chen 2019Chinese Journal of Cancer Research2019,31,1:13
2Wet-chemistry synthesis of cobalt carbide nanoparticles as highly active and stable electrocatalyst for hydrogen evolution reaction显示文摘转变金属碳化物(TMC ) nanomaterials 正在答应选择到磅,并且广泛地为电气化学的氢进化反应被用作异构的 electrocatalysts (她的) 。在这个工作,综合的导致溴化物的湿化学的策略公司 2 C nanoparticles (NP ) 被开发。如此的 NP 展出了高 electrocatalytic 活动(= 为 j = 的 181 mV 10Siwei Li Ce Yang Zhen Yin Hanjun Yang Yifu Chen Lili Lin Mengzhu Li Weizhen Li Gang HU Ding Ma 2017Nano Research2017,10,4:7
3Investigation of the tribological performance of friction pair for disc brake of drilling rig显示文摘Developing disc-brake pair materials with better performances is a key technique for thedisc brake of drilling rig. Screening experiments were carried out with five different brake-disc ma-terials in pair with two different brake-block materials. The frictional coefficient along with the cor-responding steady coefficient and fluctuating coefficient as well as the wear rate have been dis-cussed. Some conclusions have been achieved: (1) Between the two different cladding materialsbuilt-up on the steel 20~# and 35~# as brake-disc materials, the overall tribological behaviour of theone is better than that of the other. (2) Between the two brake-block composites, the one is betterthan the other. (3) Among these brake pair materials, the tribological behaviours of the second kindof brake-block composite in pair with the second build-up welding material are much better thanthat of the others, therefore, these materials can be selected preliminarily to use in disc brake fordrilling rig.ZHANG Siwei WANG Xinhua FAN Qiyun LIN Li University of Petroleum, Beijing 102200, China 2001Science China Mathematics2001,44,S1:6
4Fe5C2 nanoparticles as low-cost HER electrocatalyst:the importance of Co substitution显示文摘Constructing and understanding the doping effect of secondary metal in transition metal carbide(TMC)catalysts is pivotal for the design of low-cost hydrogen evolution reaction(HER) electrocatalysts. In this work, we developed a wet-chemistry strategy for synthesizing Co-modified Fe_5C_2 nanoparticles((Fe_(1-x)Cox)_5C_2 NPs) as highly active HER electrocatalysts in basic solution. The structure of(Fe_(1-x)Cox)_5C_2 NPs was characterized by X-ray diffraction(XRD), extended X-ray absorption fine structure spectra(EXAFS) and scanning/transmission electron microscopy(S/TEM), indicating that the isomorphous substitution of cobalt in the lattice of Fe_5C_2.(Fe_(0.75) Co_(0.25))_5C_2 exhibited the best HER activity(174 mV for j = -10 mA/cm^2). Computational calculation results indicate that Co provides the most active site for HER. X-ray adsorption spectra(XAS) studies further suggested that the electron transfer in Fe–C bonds are enhanced by the substitution of Co, which modulates the hydrogen adsorption on the adjacent electronic-enriched carbon, and therefore promotes HER activity. Our results affirm the design of lowcost bimetallic TMCs based HER catalysts.Siwei Li Pengju Ren Ce Yang Xi Liu Zhen Yin Weizhen Li Hanjun Yang Jian Li Xiaoping Wang Yi Wang Ruochen Cao Lili Lin Siyu Yao Xiaodong Wen Ding Ma 2018Science Bulletin2018,63,20:6
5Trends in Incidence Rates,Mortality Rates,and Age-Period-Cohort Effects of Cervical Cancer—China,2003–2017显示文摘Introduction:This study reported the trends and analyzed the age-period-cohort effects on the incidence and mortality rates of cervical cancer in China.Methods:The age-standardized incidence rate(ASIR)and mortality rate(ASMR)by Segi’s world standard population were calculated using qualified consecutive data from 22 cancer registries from 2003 to 2017 in China.We performed joinpoint analysis to describe the trends and age-period-cohort analysis to estimate the independent effects of age,period and cohort on trends in incidence and mortality rates of cervical cancer.Results:The ASIR and ASMR for cervical cancer in females over 20 years old increased during 2003−2017.For females<50 years,a decreasing trend in ASIR and a stable trend in ASMR were observed in urban areas after 2009.But the ASIR and ASMR kept increasing in rural areas during the whole period.For females>50 years,the ASIR and ASMR increased both in urban and rural areas.Age-period-cohort analysis showed increasing period effects on cervical cancer incidence and mortality during the whole period.The cohort effects exhibited a downward-upwarddownward pattern for the incidence(1918–1938,1938–1963,1963–1993)and mortality rates(1918–1943,1943–1963,1963–1993)in urban areas,a fluctuating pattern for incidence rate and a continuing downward pattern for mortality rate(1918–1993)in rural areas.Conclusions:The increases in cervical cancer incidence and mortality rates can be mostly explained by period effects.We observed decreases in risk for cervical cancer incidence and mortality in young female generations,which were more obvious in urban areas.Kexin Sun Rongshou Zheng Lin Lei Siwei Zhang Hongmei Zeng Shaoming Wang Li Li Ru Chen Bingfeng Han Ji Peng Wenqiang Wei Jie He 2022China CDC weekly2022,4,48:4
6Optical beam steering by using tunable,narrow-linewidth butt-coupled hybrid lasers in a silicon nitride photonics platform显示文摘Chip-scale,tunable narrow-linewidth hybrid integrated diode lasers based on quantum-dot RSOAs at 1.3μm are demonstrated through butt-coupling to a silicon nitride photonic integrated circuit.The hybrid laser linewidth is around 85 k Hz,and the tuning range is around 47 nm.Then,a fully integrated beam steerer is demonstrated by combining the tunable diode laser with a waveguide surface grating.Our system can provide beam steering of 4.1°in one direction by tuning the wavelength of the hybrid laser.Besides,a wavelength-tunable triple-band hybrid laser system working at^1,~1.3,and^1.55μm bands is demonstrated for wide-angle beam steering in a single chip.YEYU ZHU SIWEI ZENG LIN ZHU 2020Photonics Research2020,8,3:4
7Sieving carbons promise practical anodes with extensible low-potential plateaus for sodium batteries显示文摘Non-graphitic carbons are promising anode candidates for sodium-ion batteries,while their variable and complicated microstructure severely limits the rational design of high-energy carbon anodes that could accelerate the commercialization of sodium-ion batteries,as is the case for graphite in lithium-ion batteries.Here,we propose sieving carbons,featuring highly tunable nanopores with tightened pore entrances,as high-energy anodes with extensible and reversible low-potential plateaus(<0.1 V).It is shown that the tightened pore entrance blocks the formation of the solid electrolyte interphase inside the nanopores and enables sodium clustering to produce the plateau.Theoretical and spectroscopic studies also show that creating a larger area of sodiophilic pore surface leads to an almost linearly increased number of sodium clusters,and controlling the pore body diameter guarantees the reversibility of sodium cluster formation,producing a sieving carbon anode with a record-high plateau capacity of 400 mAh g.More excitingly,this approach to preparing sieving carbons has the potential to be scalable for modifying different commercial porous carbons.Qi Li Xiangsi Liu Ying Tao Jianxing Huang Jun Zhang Chunpeng Yang Yibo Zhang Siwei Zhang Yiran Jia Qiaowei Lin Yuxuan Xiang Jun Cheng Wei Lv Feiyu Kang Yong Yang Quan-Hong Yang 2022National Science Review2022,9,8:3
8Geology, Geochronology, and Hf Isotopic Composition of the Pha Lek Fe Deposit, Northern Laos: Implications for Early Permian Subduction-Related Skarn Fe Mineralization in the Truong Son Belt显示文摘The Truong Son metallogenic belt in central Laos and Vietnam is an important Fe-Cu-Sn-Au polymetallic ore district. The Pha Lek Fe deposit is closely related to Late Carboniferous– Early Permian I-type granitic magmatism, and contains >50 Mt @ 45% to 50% of Fe ore. Ore minerals occur mainly as magnetite and hematite in the skarn alteration zone between a granitic pluton and metamorphosed Middle–Upper Devonian carbonates. The granitic pluton comprises granodiorite and granite, with zircon U-Pb dating indicating synchronous emplacement at 288.2±1.3 and 284.9±1.2 Ma, respectively. Zircons from these granitoids have ε_(Hf)(t) values of 2.9–11.2 and relatively young TDM2 ages(<1.0 Ga), indicating an origin by partial melting of depleted mafic crust or magma mixing. Previous studies have shown that these granitoids have high Y, Yb, and K_2O contents, and low Sr and Na_2O contents, which are interpreted as the melting of mafic continental crust. Pyrite of the main mineralization stage yields an ^(187)Re/^(188)Os-^(187)Os/^(188)Os isochron age of 287±17 Ma, indicating that mineralization is associated with Pha Lek granitic magmatism. A Late Carboniferous–Early Permian subduction-related skarn-type Fe mineralization model is proposed for the Pha Lek deposit. More evidence is needed to verify a hypothesis of volcanic overprinting during Late Triassic post-collisional extension.Lin Hou Shusheng Liu Linnan Guo Fuhao Xiong Chao Li Meifeng Shi Qiming Zhang Siwei Xu Songyang Wu 2019Journal of Earth Science2019,30,1:2
9Meiotic nuclear divisions 1(MND1)fuels cell cycle progression by activating a KLF6/E2F1 positive feedback loop in lung adenocarcinoma显示文摘Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD.Methods:The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus(GEO)datasets and The Cancer Genome Atlas(TCGA)data were combined,and a promising risk biomarker called meiotic nuclear divisions 1(MND1)was selectively acquired.Cell viability assays and subcutaneous xenograftmodelswere used to validate the oncogenic role ofMND1 in LUADcell proliferation and tumor growth.Aseries of assays,including mass spectrometry,co-immunoprecipitation(Co-IP),and chromatin immunoprecipitation(ChIP),were performed to explore the underlying mechanism.Results:MND1 up-regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis.In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle.The results of the Co-IP,ChIP and dual-luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel-like factor 6(KLF6),and thereby protecting E2F transcription factor 1(E2F1)from KLF6-induced transcriptional repression.Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner.Conclusions:MND1,KLF6,and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD.MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.Quanli Zhang Run Shi Yongkang Bai Lijuan Meng Jingwen Hu Hongyu Zhu Tongyan Liu Xiaomeng De Siwei Wang Jie Wang Lin Xu Guoren Zhou Rong Yin 2021Cancer Communications2021,41,6:2
10LncRNA LINC00525 suppresses p21 expression viamRNA decay and triplex-mediated changes in chromatin structure in lung adenocarcinoma显示文摘Background:Emerging evidence suggests that long noncoding RNAs(lncRNAs)play crucial roles in various cancers.In the present study,we aim to investigate the function and molecular mechanism of an up-regulated and survivalassociated lncRNA,LINC00525,in lung adenocarcinoma(LUAD).Methods:The expression level of LINC00525 in tissueswas determined by quantitative reverse transcription polymerase chain reaction(RT-qPCR)and in situ hybridization(ISH).The functional role of LINC00525 in LUAD was investigated using gain-and loss-of-function approaches,both in vivo and in vitro.RNA pull-down,RNA immunoprecipitation(RIP),chromatin immunoprecipitation(ChIP),triplex-capture assay,dual-luciferase assay,gene expression microarray,and bioinformatics analysis were used to investigate the potential underlying mechanisms involved.Results:LINC00525 is highly expressed in LUAD cells and tissues.Survival analysis indicated that upregulation of LINC00525 was associated with poor prognosis in patients with LUAD patients.Knockdown of LINC00525 inhibited cell proliferation and cell cycle progression in vitro.In xenograft models,LINC00525 knockdown suppressed tumor growth and tumorigenesis of tumorbearing mice.Mechanistically,LINC00525 epigenetically suppressed p21 transcription by guiding Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit(EZH2)to the p21 promoter through an formation of RNA-DNA triplex with the p21 promoter,leading to increased trimethylation of lysine 27 on histone 3(H3K27me3)of the p21 promoter.In addition,LINC00525 repressed p21 expression post-transcriptionally by enhancing p21mRNA decay.LINC00525 promoted p21mRNAdecay by competitively binding toRNABindingMotif Single Stranded Interacting Protein 2(RBMS2).Conclusion:Our findings demonstrate that LINC00525 promotes the progression of LUAD by reducing the transcription and stability of p21 mRNA in concert with EZH2 and RBMS2,thus suggesting that LINC00525 may be a potential therapeutic target for clinical intervention in LUAD.Panqi Fang Hao Chen Zhifei Ma Chencheng Han Wenda Yin Siwei Wang Hongyu Zhu Wenjia Xia Jie Wang Lin Xu Tongyan Liu Rong Yin 2021Cancer Communications2021,41,7:2
11Trends in Incidence Rates,Mortality Rates,and Age-Period-Cohort Effects of Female Breast Cancer—China,2003-2017显示文摘Introduction:This study reported the trends in female breast cancer incidence and mortality rates in China,and analyzed the corresponding age-periodcohort effects.Methods:Data from 22 population-based cancer registries in China between 2003 and 2017 were analyzed.Age-standardized incidence rates(ASIR)and mortality rates(ASMR)were calculated using Segi’s world standard population.Joinpoint regression was employed to evaluate trends,and age-period-cohort effects were examined using the intrinsic estimator method.Results:The ASIR for female breast cancer exhibited a more rapid increase in rural areas compared to urban areas across all age groups.The most substantial increase was observed in the 20-34 age group in rural areas[annual percent change(APC)=9.0%,95%confidence interval(CI):7.0%-11.0%,P<0.001].The ASMR for females under 50 years old remained stable from 2003 to 2017 in both urban and rural areas.However,the ASMR for females over 50 in rural areas and those over 65 in urban areas demonstrated a significant increase,with the most pronounced increase observed among females over 65 in rural areas(APC=4.9%,95%CI:2.8%-7.0%,P<0.001).Age-period-cohort analysis revealed increasing period effects and decreasing cohort effects for female breast cancer incidence and mortality rates in both urban and rural settings.Notably,the cohort effect for incidence displayed a slight upward trend for females born between 1983 and 1992 in rural areas.Conclusions:Our study revealed a rapid increase in breast cancer incidence among younger generations and an accelerated mortality rate in older populations residing in rural areas.To effectively address the growing burden of female breast cancer in China,it is essential to develop and implement targeted intervention strategies.Kexin Sun Lin Lei Rongshou Zheng Siwei Zhang Hongmei Zeng Shaoming Wang Li Li Ru Chen Bingfeng Han Ji Peng Wenqiang Wei Jie He 2023China CDC weekly2023,5,15:1
12Thermometry strategy developed based on fluorescence contrast driven by varying excitations in codoped LiNbO3显示文摘We propose what we believe is a novel optical thermometry strategy(FIR-Ex)based on the fluorescence intensity ratio(FIR)between two radiations associated with the same emission peak but different excitation wavelengths,in contrast to the traditional approach(FIR-Em),which depends on the FIR at varying emission wavelengths.The temperature-dependent FIR within the FIR-Ex strategy arises from the different charge/energy evolution routes,rather than the distribution of thermally coupled levels within the FIR-Em strategy.Considerable diversity in thermal behaviors and luminescence mechanisms was demonstrated by analyzing the 618 nm red emission in Pr^3+-doped congruent LiNbO3(Pr:CLN)under 360 and 463 nm excitations.The temperature sensitivity was further improved via Mg^2+ codoping due to the optimization of charge dynamics and energy transfer processes.Given its wide detection scope,relatively high absolute sensitivity at low temperature,and high tunability of temperature sensitivity,the FIR-Ex strategy is promising for developing optical temperature-sensing materials with high performance.SIWEI LONG SHAOPENG LIN DECAI MA YUNZHONG ZHU HUASHAN LI BIAO WANG 2020Photonics Research2020,8,2:1
13New Design of Shape Memory Polymers Based on Natural Rubber Crosslinked via Oxa-Michael Reaction显示文摘Lin Tengfei Ma Siwei Lu Yang 2014Applied Materials and Interfaces2014,6,8:1
14Causes and Enlightenments on M&A in International Banking显示文摘Lin Zhou Qiusheng Zhang Siwei Zhou 2004China-USA Business Review2004,3,1:0
15Several Queries about the Weston Model of Valuation in M & A显示文摘Lin Zhou Qiusheng Zhang Siwei Zhou 2004China-USA Business Review2004,3,2:0
16Manipulating oxygenate adsorption on N-doped carbon by coupling with CoSn alloy for bifunctional oxygen electrocatalyst显示文摘Highly active bifunctional oxygen electrocatalysts accelerate the development of high-performance Zn-air battery,but suffer from the mismatched activities of oxygen evolution reaction(OER)and oxygen reduced reaction(ORR).Herein,highly integrated bifunctional oxygen electrocatalysts,cobalt-tin alloys coated by nitrogen doped carbon(CoSn@NC)are prepared by MOFs-derived method.In this hybrid catalyst,the binary CoSn nanoalloys mainly contribute to highly active OER process while the Co(or Sn)-N-C serves as ORR active sites.Rational interaction between CoSn and NC donates more rapid reaction kinetics than Pt/C(ORR)and IrO_(2)(OER).Such CoSn@NC holds a promise as air-cathode electrocatalyst in Zn-air battery,superior to Pt/C+IrO_(2)catalyst.First-principles calculations predict that CoSn alloys can upgrade charge redistribution on NC and promote the transfer to reactants,thus optimizing the adsorption strength of oxygen-containing intermediates to boost the overall reactivity.The tuning of oxygenate adsorption by interactions between alloy and heteroatom-doped carbon can guide the design of bifunctional oxygen electrocatalysts.Chenlong Dong Xilin Zhang Shaoning Zhang Siwei Zhao Xueyu Lin Xin Wang Yajing Zhang Fuqiang Huang 2023Green Energy & Environment2023,8,5:0
17Investigation on occupant presence and appliance operation schedules for university campus in south China sub-tropical area显示文摘Building occupant presence during varying periods is crucial to the performance studies of buildings and city regions.However,the understanding of the building occupancies on the university campus remains limited.To address this gap,our study employs field measurements,payment records,course arrangements,and building access systems to depict the occupancy patterns of the canteen,dormitory,library,and teaching and lab buildings during weekdays and weekends.We found that the occupancy rates across different buildings are somehow interrelated,given that the total number of occupants on campus is generally constant.Notably,dormitory occupancy rates tend to be low during the morning and afternoon course hours,which inversely correlates with the high occupancy rates in the teaching and lab buildings during these periods.Similarly,canteens experience surges in occupancy during meal times,which coincide with a decrease in library usage.Moreover,we established appliance operation schedules for dormitories through surveys and on-site investigations.Water dispensers and electronic devices were identified as the primary energy consumers for both male and female occupants,with desk-top fans and hairdryers being significant energy users for male and female occupants,respectively.These findings are essential for energy studies within a campus setting,underlining the importance of considering occupant behaviors on a regional scale.Siwei Lou Zhongyuan Lin Yukai Zou Dawei Xia Yu Huang Zhuohong Li Zhaowen Gu 2024Building Simulation2024,17,2:0
18Direct utilization of crude and waste H_(2) via CO-tolerant hydrogenation显示文摘H_(2) tends to be a crucial medium in the foreseeable future as it is not only a green and renewable energy source for vehicles but also a fundamental feedstock for the chemical industry.For instance,selective hydrogenation,one of the catalytic processes used to produce fine compounds,is of vital importance because it enables the selective and efficient conversionof a variety of functional groups under mild reaction conditions.Catalytic hydrogenation of liquid organic hydrogen carriers(LOHCs;eg,methylbenzene)is a safe and economic approach for H_(2) storage.Siwei Li Lili Lin Zhaohua Wang Ding Ma 2023The Innovation2023,4,1:0
19Design of luminescence in(Sr,Gd)Li(Al,Mg)_(3)N_(4):Eu^(2+)deep red phosphors via crystal field engineering for full-spectrum WLEDs显示文摘Red phosphor,with longer wavelength,is highly desirable for full-spectrum WLEDs.Targeted deep red phosphors(Sr,Gd)Li(AI,Mg)_(3)N_(4):Eu^(2+)were designed from the initial model of SrLiAl_(3)N_(4):Eu^(2+)by structural modification.The correlations among structural evolution,crystal-field environment,and luminescence properties were elucidated.Replacing Sr^(2+)with Gd^(3+)in(Sr,Gd)LiAl_(3)N_(4):Eu^(2+)leads to the enhanced crystal field splitting,larger Stokes shift,and increased structural polyhedron distortion differences,consequently resulting in spectral red-shift and broadening.For further spectral tuning,Mg,with lower electronegativity,was also introduced to modify the local crystal structure,consequently resulting in a further red-shift towards 675 nm and enhanced photoluminescence intensity in(Sr,Gd)Li(AI,Mg)_(3)N_(4):Eu^(2+).What’s more,w-LEDs were fabricated by using blue LED chip,blue,green,red and deep red((Sr,Gd)Li(Al,Mg)_(3)N_(4):Eu^(2+))phosphors whose color rendering index were Ra 96.0 and R997.7.All above results demonstrate that the partial replacements of Sr^(2+)by Gd^(3+)and Al^(3+)by Mg^(2+)are effective methods for spectral modulation and(Sr,Gd)Li(AI,Mg)_(3)N_(4):Eu^(2+)phosphors are suitable for highquality full-spectrum WLEDs.Qing Lin Tongyu Gao Yuanhong Liu Ronghui Liu Siwei Chen Xiaole Ma Chunlei Zhao 2023Journal of Rare Earths2023,41,8:0
20Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate显示文摘Glycolytic intermediary metabolites such as fructose-1,6-bisphosphate can serve as signals,controlling metabolic states beyond energy metabolism.However,whether glycolytic metabolites also play a role in controlling cell fate remains unexplored.Here,we find that low levels of glycolytic metabolite 3-phosphoglycerate(3-PGA)can switch phosphoglycerate dehydrogenase(PHGDH)from cataplerosis serine synthesis to pro-apoptotic activation of p53.PHGDH is a p53-binding protein,and when unoccupied by 3-PGA interacts with the scaffold protein AXIN in complex with the kinase HIPK2,both of which are also p53-binding proteins.This leads to the formation of a multivalent p53-binding complex that allows HIPK2 to specifically phosphorylate p53-Ser46 and thereby promote apoptosis.Furthermore,we show that PHGDH mutants(R135W and V261M)that are constitutively bound to 3-PGA abolish p53 activation even under low glucose conditions,while the mutants(T57A and T78A)unable to bind 3-PGA cause constitutive p53 activation and apoptosis in hepatocellular carcinoma(HCC)cells,even in the presence of high glucose.In vivo,PHGDH-T57A induces apoptosis and inhibits the growth of diethylnitrosamine-induced mouse HCC,whereas PHGDH-R135W prevents apoptosis and promotes HCC growth,and knockout of Trp53 abolishes these effects above.Importantly,caloric restriction that lowers whole-body glucose levels can impede HCC growth dependent on PHGDH.Together,these results unveil a mechanism by which glucose availability autonomously controls p53 activity,providing a new paradigm of cell fate control by metabolic substrate availability.Yu-Qing Wu Chen-Song Zhang Jinye Xiong Dong-Qi Cai Chen-Zhe Wang Yu Wang Yan-Hui Liu Yu Wang Yiming Li Jian Wu Jianfeng Wu Bin Lan Xuefeng Wang Siwei Chen Xianglei Cao Xiaoyan Wei Hui-Hui Hu Huiling Guo Yaxin Yu Abdul Ghafoor Changchuan Xie Yaying Wu Zheni Xu Cixiong Zhang Mingxia Zhu Xi Huang Xiufeng Sun Shu-Yong Lin Hai-Long Piao Jianyin Zhou Sheng-Cai Lin 2023Cell Research2023,33,11:0
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