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Roles of THEM4 in the Akt pathway:a double-edged sword

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 541-556页

作者： Wen XIE Weidong liu Lei WANG Bin ZHU cong ZHAO Ziling LIAO Yihan LI Xingjun JIANG Jie liu Caiping REN NHC Key Laboratory of Carcinogenesis Department of NeurosurgeryXiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China The Key Laboratory of Carcinogenesis and Cancer Invasion of the Ministry of Education Cancer Research InstituteSchool of Basic Medical ScienceCentral South UniversityChangsha 410078China Department of Critical Care Medicine Hainan Hospital of Chinese PLA General HospitalHainan Province Clinical Medical CenterSanya 572013China

The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of *** superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding *** studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its ***,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous *** these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially *** work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

关键词： Protein kinase B(Akt) Thioesterase superfamily member 4(THEM4) Tumor proliferation Tumor metastasis

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The global regulation of c-di-GMP and cAMP in bacteria

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mLife 2024年第1期3卷 42-56页

作者： cong liu Rui Shi Marcus S.Jensen Jingrong Zhu Jiawen liu xiaobo liu Di Sun Weijie liu Jiangsu Key Laboratory of Phylogenomics&Comparative Genomics School of Life SciencesJiangsu Normal UniversityXuzhouChina Key Laboratory of Metabolic Engineering and Biosynthesis Technology Ministry of Industry and Information TechnologyNanjing University of Science and TechnologyNanjingChina

Nucleotide second messengers are highly versatile signaling molecules that regulate a variety of key biological processes in *** best-studied examples are cyclic AMP(cAMP)and bis-(3'-5')-cyclic dimeric guanosine monophosphate(c-di-GMP),which both act as global *** regulatory frameworks of c-di-GMP and cAMP in bacteria show several parallels but also significant *** this review,we llustrate the global regulatory models of the two nucleotide second messengers,compare the different regulatory frameworks between c-di-GMP and cAMP,and discuss the mechanisms and physiological significance of cross-regulation between c-di-GMP and cAMP.c-di-GMP responds to numerous signals de-pendent on a great number of metabolic enzymes,and it regulates various signal transduction pathways through its huge number of effectors with varying *** contrast,due to the limited quantity,the cAMP metabolic enzymes and its major effector are regulated at different levels by diverse *** performs its global regulatory function primarily by controlling the transcription of a large number of genes via cAMP receptor protein(CRP)in most *** review can help us understand how bacteria use the two typical nucleotide second messengers to effectively coordinate and integrate various physiological processes,providing theoretical guidelines for future research.

关键词： bacteria cAMP c-di-GMP cross-regulation CRP

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A quantitative study of disruptive technology policy texts:An example of China’s artificial intelligence policy

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Journal of Data and Information Science 2024年第3期9卷 155-180页

作者： Ying Zhou Linzhi Yan xiao liu School of Management Anhui UniversityHefei 230601China

Purpose:The transformative impact of disruptive technologies on the restructuring of the times has attracted widespread global *** study aims to analyze the characteristics and shortcomings of China’s artificial intelligence(AI)disruptive technology policy,and to put forward suggestions for optimizing China’s AI disruptive technology ***/methodology/approach:Develop a three-dimensional analytical framework for“policy tools-policy actors-policy themes”and apply policy tools,social network analysis,and LDA topic model to conduct a comprehensive analysis of the utilization of policy tools,cooperative relationships among policy actors,and the trends in policy theme settings within China’s innovative AI technology ***:We find that the collaborative relationship among the policy actors of AI disruptive technology in China is insufficiently *** subjects exhibit low participation in the cooperation network and overly rely on central subjects,forming a“center-periphery”network *** tool usage is predominantly focused on supply and environmental types,with a severe inadequacy in demand-side policy tool *** themes are diverse,encompassing topics such as“Intelligent Services”“Talent Cultivation”“Information Security”and“Technological Innovation”,which will remain focal *** the themes of“Intelligent Services”and“Intelligent Governance”,policy tool usage is relatively balanced,with close collaboration among policy ***,the theme of“AI Theoretical System”lacks a comprehensive understanding of tool usage and necessitates enhanced cooperation with other policy *** limitations:The data sources and experimental scope are subject to certain limitations,potentially introducing biases and imperfections into the research results,necessitating further validation and *** implications:The study introduces a three-dimensional analysis framework for disruptive technology p

关键词： Disruptive technologies Artificial intelligence Synergies Policy tools Thematic evolution

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Total ionizing dose effect modeling method for CMOS digital-integrated circuit

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Nuclear Science and Techniques 2024年第2期35卷 32-46页

作者： Bo Liang Jin-Hui liu xiao-Peng Zhang Gang liu Wen-Dan Tan Xin-Dan Zhang School of Computer Science and Technology Xidian UniversityXi’an 710071China

Simulating the total ionizing dose(TID)of an electrical system using transistor-level models can be difficult and expensive,particularly for digital-integrated circuits(ICs).In this study,a method for modeling TID effects in complementary metaloxide semiconductor(CMOS)digital ICs based on the input/output buffer information specification(IBIS)was *** digital IC was first divided into three parts based on its internal structure:the input buffer,output buffer,and functional *** of these three parts was separately *** the IBIS model,the transistor V-I characteristic curves of the buffers were processed,and the physical parameters were extracted and modeled using *** the functional area,logic functions were modeled in VHDL according to the data sheet.A golden digital IC model was developed by combining the input buffer,output buffer,and functional area ***,the golden ratio was reconstructed based on TID experimental data,enabling the assessment of TID effects on the threshold voltage,carrier mobility,and time series of the digital *** experiments were conducted using a CMOS non-inverting multiplexer,NC7SZ157,and the results were compared with the simulation results,which showed that the relative errors were less than 2%at each dose *** confirms the practicality and accuracy of the proposed modeling *** TID effect model for digital ICs developed using this modeling technique includes both the logical function of the IC and changes in electrical properties and functional degradation impacted by TID,which has potential applications in the design of radiation-hardening tolerance in digital ICs.

关键词： CMOS digital-integrated circuit Total ionizing dose IBIS model Behavior-physical hybrid model Physical parameters

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FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression

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International Journal of Oral Science 2024年第2期16卷 333-348页

作者： Zhonglong liu xiaoyan Meng Yuxin Zhang Jingjing Sun xiao Tang Zhiyuan Zhang liu liu Yue He Department of Oral Maxillofacial&Head and Neck Oncology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseaseShanghaiChina Department of Oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghaiChina Department of Oral Pathology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral Disease ShanghaiShanghaiChina

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor *** glycosylation has been intricately linked with immune escape and tumor ***7A is a highly glycosylated protein with five glycosylated *** underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are ***,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the *** EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal *** N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell *** of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based ***,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative *** findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

关键词： aberrant squamous SEMA

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Lotus root-like RuIr alloys with close-packed(0001)branches:Strain-driven performance for acidic water oxidation

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Journal of Energy Chemistry 2024年第5期92卷 579-590页

作者： Mingyue xiao Wanli Xu Rongchao Li Yanhui Sun Jingjun liu Feng liu Jun Gan Shixin Gao Beijing Key Laboratory of Electrochemical Process and Technology for Materials Beijing University of Chemical TechnologyBeijing 100029China Yunnan Precious Metals Lab Kunming 650100YunnanChina

Achieving composition tunability and structure editability of nanoalloys with high level strain may be an efficient strategy to remarkably boost catalytic performance toward oxygen evolution reaction(OER)in acidic water ***,lotus root-like RuIr alloys with native micro-strain were constructed by an epitaxial growth of Ru-richened hcp-(0001)branches on Ir-richened fcc-(111)seeds using a polyol thermal synthesis *** resultant Ru_(60)Ir_(40) alloy shows an OER overpotential of 197 mV at 10 mA cm^(-2) and a Tafel slope of 46.59 mV dec^(-1),showing no obvious activity decay for 80 h continuous chronopotentiometry test in 0.5 M H_(2)SO_(4).The related characterizations including X-ray absorption fine structure(XAFS)spectroscopy and density functional theory(DFT)calculations show that that the remarkably improved activity of the lotus root-like alloy can be attributed to the(0001)facet-triggered strain,which can efficiently optimize the electronic band structure of the active metal and the weakening of the chemisorption of oxygen-containing substances to boost OER ***,this work provides a new strategy to designing a class of advanced electrocatalysts with high strain using diverse nanostructures as building materials for carbon-free clean energy conversion systems.

关键词： Rulr alloy Lotusroot-like structure Strain Oxygene volution reaction Activity

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The Largest Chinese Cohort Study Indicates Homologous Recombination Pathway Gene Mutations as Another Major Genetic Risk Factor for Colorectal Cancer with Heterogeneous Clinical Phenotypes

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Research 2024年第3期6卷 191-203页

作者： Yun Xu Kai liu cong Li Minghan Li Fangqi liu xiaoyan Zhou Menghong Sun Megha Ranganathan Liying Zhang Sheng Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Fudan University Shanghai Cancer CenterShanghaiP.R.China Department of Pathology Tissue BankFudan University Shanghai Cancer CenterShanghaiP.R.China Department of Medicine Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Pathology and Laboratory Medicine David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA Precision Cancer Medical Center Fudan University Shanghai Cancer CenterShanghaiP.R.China

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

关键词： susceptibility category Major

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Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication

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Zoological Research 2024年第5期45卷 990-1000页

作者： Zhi-Min Li xiao-Wei Qin Qi Zhang Jian He Min-cong Liang Chuan-Rui Li Yang Yu Weng-Hui liu Shao-Ping Weng Jian-Guo He Chang-Jun Guo School of Marine Sciences State Key Laboratory for BiocontrolSouthern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Guangdong Province Key Laboratory of Aquatic Economic Animals&Guangdong Provincial Observation and Research Station for Marine Ranching of the Lingdingyang BaySun Yat-sen UniversityGuangzhouGuangdong 510275China Guangdong Laboratory for Lingnan Modern Agriculture South China Agricultural UniversityGuangzhouGuangdong 510640China

The von Hippel-Lindau tumor suppressor protein(VHL),an E3 ubiquitin ligase,functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible *** evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway,although the specific molecular mechanisms remain ***,the roles of mandarin fish(Siniperca chuatsi)VHL(scVHL)in the NF-κB signaling pathway and mandarin fish ranavirus(MRV)replication were *** transcription of scVHL was induced by immune stimulation and MRV infection,indicating a potential role in innate ***-luciferase reporter gene assays and reverse transcription quantitative PCR(RT-qPCR)results demonstrated that scVHL evoked and positively regulated the NF-κB signaling *** with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα,scIKKβ,scIκBα,or ***-immunoprecipitation(Co-IP)analysis identified scIκBαas a novel target protein of ***,scVHL targeted scIκBαto catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling *** MRV infection,NF-κB signaling remained activated,which,in turn,promoted MRV *** findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV *** study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

关键词： VHL NF-κB IκBα Ranavirus Mandarin fish

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Influence of topography on the fine structures of stratospheric gravity waves:An analysis using COSMIC-2 temperature data

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Earth and Planetary Physics 2024年第3期8卷 497-513页

作者： JiaRui Wei xiao liu JiYao Xu QinZeng Li Hong Gao State Key Laboratory of Space Weather National Space Science CenterChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Institute of Electromagnetic Wave School of PhysicsHenan Normal UniversityXinxiang Henan 453000China

We derive the potential energy of gravity waves(GWs)in the upper troposphere and stratosphere at 45°S-45°N from December 2019 to November 2022 by using temperature profiles retrieved from the Constellation Observing System for Meteorology,Ionosphere,and Climate-2(COSMIC-2)*** to the dense sampling of COSMIC-2,in addition to the strong peaks of gravity wave potential energy(GWPE)above the Andes and Tibetan Plateau,we found weak peaks above the Rocky,Atlas,Caucasus,and Tianshan *** land-sea contrast is responsible for the longitudinal variations of the GWPE in the lower and upper *** 40°N/S,the peaks were mainly above the topographic regions during the *** 20°N/S,the peaks were a slight distance away from the topographic regions and might be the combined effect of nontopographic GWs and mountain *** the Equator,the peaks were mainly above the regions with the lowest sea level altitude and may have resulted from *** results indicate that even above the local regions with lower sea level altitudes compared with the Andes and Tibetan Plateau,the GWPE also exhibits fine structures in geographic *** found that dissipation layers above the tropopause jet provide the body force to generate secondary waves in the upper stratosphere,especially during the winter months of each hemisphere and at latitudes of greater than 20°N/S.

关键词： topography fine structures stratospheric gravity waves Constellation Observing System for Meteorology Ionosphere and Climate-2(COSMIC-2) dissipation layers

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Sparse-view neutron CT 3D image reconstruction algorithm based on split Bregman method

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Nuclear Science and Techniques 2024年第9期35卷 41-55页

作者： Teng-Fei Zhu Yang liu Zhi Luo xiao-Ping Ouyang School of Nuclear Science and Engineering North China Electric Power UniversityBeijing 102206China State Key Laboratory of Nuclear Resources and Environment East China University of TechnologyNanchang 330013China State Key Laboratory of Intense Pulsed Radiation Simulation and Effect Xi’an 710024China

As a complement to X-ray computed tomography(CT),neutron tomography has been extensively used in nuclear engineer-ing,materials science,cultural heritage,and industrial *** of the attenuation matrix for neutron tomography with a traditional analytical algorithm requires hundreds of projection views in the range of 0°to 180°and typically takes several hours to *** a low time-resolved resolution degrades the quality of neutron *** the number of projection acquisitions is an important approach to improve the time resolution of images;however,this requires efficient reconstruction ***,sparse-view reconstruction algorithms in neutron tomography need to be *** this study,we investigated the three-dimensional reconstruction algorithm for sparse-view neu-tron CT *** enhance the reconstructed image quality of neutron CT,we propose an algorithm that uses OS-SART to reconstruct images and a split Bregman to solve for the total variation(SBTV).A comparative analysis of the performances of each reconstruction algorithm was performed using simulated and actual experimental *** to the analyzed results,OS-SART-SBTV is superior to the other algorithms in terms of denoising,suppressing artifacts,and preserving detailed structural information of images.

关键词： Neutron CT OS-SART Sparse-view 3D reconstruction Split Bregman Total variation

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