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Alkyl Radical Initiated Cyclization/Cascade for Synthesizing Lactam-Substituted Alkyl Sulfones

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Chinese Journal of Chemistry 2024年第16期42卷 1853-1859页

作者： Li-Jun wu Kai-Yi zhang Pei Yang Chuan-Chong Peng Jin-Hui Liu qing Li Da-Zhi Sun Shuangfeng Yin College of Sciences Central South University of Forestry and TechnologyChangshaHunan410004 China School of Chemistry and Chemical Engineering Inner Mongolia UniversityHohhotInner Mongolia010021 China

An alkyl radical initiated cyclization/tandem reaction of alkyl bromides and alkyl electrophiles by using potassium metabisulphite(K_(2.S_(2.O_(5))as a connector is developed for the synthesis of various lactam-substituted alkyl ***,this process does not require a metal catalyst or metal powder reductant,highlighting its environmentally friendly *** reaction demonstrates outstanding substrate adaptability and a high tolerance towards diverse functional ***,the biologically active molecules and commercially available drugs with a late-stage modification are also highly compatible with this *** studies revealed that the reaction proceeds through a single-step process involving intramolecular radical cyclization,"SO_(2."insertion,and external alkyl incorporation.

关键词： Alkyl radical Metal-free catalyzed Cyclization/cascade Potassium metabisulphite Electrophiles Alkyl sulfones Lactams Alkyl bromides Sodium formate

Early-onset and later-onset cancer:trends,risk factors,and prevention in Northern China

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Science China(Life Sciences) 2024年第9期67卷 1928-1940页

作者： Tong Liu Chen-An Liu qing-Song zhang Qi zhang Yi-Ming Wang Meng-Meng Song Shi-Qi Lin Li Deng Shou-Ling wu Han-Ping Shi Department of Gastrointestinal Surgery Department of Clinical NutritionBeijing Shijitan HospitalCapital Medical UniversityBeijing 100038China National Clinical Research Center for Geriatric Diseases Xuanwu HospitalCapital Medical UniversityBeijing 100053China Key Laboratory of Cancer FSMP for State Market Regulation Beijing 100038China Laboratory for Clinical Medicine Capital Medical UniversityBeijing 100038China Department of General Surgery Kailuan General HospitalTangshan 063000China Department of Genetics Yale School of MedicineNew Haven 06510USA Department of Hepatobiliary Surgery Kailuan General HospitalTangshan 063000China Cardiovascular Research institute University of CaliforniaSan Francisco 94158USA Department of Cardiology Kailuan General HospitalTangshan 063000China

The characteristics of early-onset(onset age<50 years)and later-onset(onset age≥50 years)cancers differ *** novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for... 详细信息

The characteristics of early-onset(onset age2. with early-onset cancer and 6,117 with later-onset cancer)and 6,780 matched controls among the 186,2.9 participants who underwent Kailuan health examinations from 2.06 to *** primary outcomes were cancer incidence rates,and associated risk factors for early-and later-onset *** Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early-and later-onset cancer by cancer *** risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the *** for liver cancer,incidence rates for nearly all types of cancer increased during the study ***,alcohol consumption,lipid metabolism disorders,hypertension,diabetes mellitus,fatty liver,and inflammation were associated with a significantly increased risk of cancer at multiple sites,but risk factors for cancer incidence differed by ***,alcohol consumption,inflammation,and hypertension were the major contributors to preventable *** incidence of several different types of cancer,including earlyonset cancer,is increasing in northeastern *** in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

关键词： cancer early-onset later-onset trend risk factor prevention

Contactin-associated protein-like 2.CNTNAP2.mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： qing zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing zhang Zhe Wang Yili wu Yun zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2.CNTNAP2.gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2.protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2.remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2.undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2.locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2.intracellular domain(CICD).ASD-associated CNTNAP2.mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2.12.4T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2.(112.4T) knock-in and Cntnap2.(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2.processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

Experimental Study on Hydrodynamic Load Characteristics for A Typical Cross-Section of A Submerged Floating Tunnel

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China Ocean Engineering 2024年第5期38卷 893-903页

作者： zhang Hong-qian YANG Zhi-wen LI Shao-wu YUAN Chun-guang zhang Hua-{2. National Engineering Research Center for Port Hydraulic Construction Technology Tianjin University National Engineering Research Center for Port Hydraulic Construction Technology Tianjin Research Institute for Water Transport EngineeringM.O.T.

The typical cross-sectional form of a submerged floating tunnel plays a significant role in the dynamic response of the tunnel itself,which directly affects the overall *** this work,a series of experiments involving wave action on a submerged floating tube cross section is reported to study its hydrodynamic load *** typical cross section tube cylinders,circular and rectangular,are *** are carried out in a wave flume with waves of relatively low Keulegan-Carpenter（KC） *** relative depths of submergence of 0,0.2. and 0.5are *** measured wave forces in regular waves are used to analyze the horizontal force,vertical force and torque,and then the drag coefficient（Cd） and inertia coefficient（Cm） are *** results show that the drag coefficients at low KC numbers are large and decrease sharply with increasing KC *** inertial coefficient Cmvalues in the vertical direction are about 70% larger than those in the horizontal *** an increase in aspect ratio（the ratio of the height to width of the structure）,the ratio of inertia coefficient in the horizontal direction to that in the vertical direction increases *** inertia force coefficient is very sensitive to the submerged water depth and aspect *** existing results may overestimate the actual force value.

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A compact multi-pixel superconducting nanowire single-photon detector array supporting gigabit space-to-ground communications

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Light(Science & Applications) 2024年第2期13卷 254-266页

作者： Hao Hao qing-Yuan Zhao Yang-Hui Huang Jie Deng Fan Yang Sai-Ying Ru Zhen Liu Chao Wan Hao Liu Zhi-Jian Li Hua-Bing Wang Xue-Cou Tu La-Bao zhang Xiao-qing Jia Xing-Long wu Jian Chen Lin Kang Pei-Heng wu Research institute of Superconductor Electronics(RISE) School of Electronic Science and EngineeringNanjing UniversityNanjingJiangsu 210023China Purple Mountain Laboratories NanjingJiangsu 211111China Hefei National Laboratory HefeiAnhui 230088China National Laboratory of Solid State Microstructures and Department of Physics Nanjing UniversityNanjing 210023China

Classical and quantum space-to-ground communications necessitate highly sensitive receivers capable of extracting information from modulated photons to extend the communication distance from near-earth orbits to deep space *** achieve gigabit data rates while mitigating strong background noise photons and beam drift in a highly attenuated free-space channel,a comprehensive design of a multi-functional detector is *** this study,we present an innovative compact multi-pixel superconducting nanowire single-photon detector array that integrates near-unity detection efficiency(91.6%),high photon counting rate(1.61 Gcps),large dynamic range for resolving different photon numbers(1-2.),and four-quadrant position sensing function all within one ***,we have constructed a communication testbed to validate the advantages offered by such an *** 8-PPM(pulse position modulation)format communication experiments,we have achieved an impressive maximum data rate of 1.5 Gbps,demonstrating sensitivities surpassing previous benchmarks at respective *** incorporating photon number information into error correction codes,the receiver can tolerate maximum background noise levels equivalent to 0.8 photons/slot at a data rate of 12. Mbps—showcasing a great potential for daylight operation ***,preliminary beam tracking tests were conducted through open-loop scanning techniques,which revealed clear quantitative dependence indicating sensitivity variations based on beam *** on the device characterizations and communication results,we anticipate that this device architecture,along with its corresponding signal processing and coding techniques,will be applicable in future space-to-ground communication tasks.

关键词： photon supporting correction

Two stages power generation test of the hot dry rock exploration and production demonstration project in the Gonghe Basin,northeastern qinghai-Tibet plateau,China

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China Geology 2024年第3期7卷 409-421页

作者： Er-yong zhang Dong-guang Wen Gui-ling Wang Xian-peng Jin Lin-you zhang Hai-dong wu Wen-shi Wang Cheng-ming Ye Wei Weng Kuan Li Jin-sheng wu Xian-chun Tang Chong-yuan zhang qing-da Feng Sheng Lian Li-sha Hu Gui-lin Zhu Xing-long Xie Bin wu Dan Wang Xue Niu Zhao-xuan Niu Dong-lin Liu Hui zhang Wen-hao Xu Shu-qing Yao Li Yang Center for Hydrogeology and Environmental Geology Survey China Geological SurveyMinistry of Natural ResourcesTianjin 300304China institute of Hydrogeology and Environmental Geology Chinese Academy of Geological SciencesChina Geological SurveyShijiazhuang 050061China institute of Exploration Techniques Chinese Academy of Geological SciencesChina Geological SurveyLangfang 065000China institute of Exploration Engineering China Geological SurveyMinistry of Natural ResourcesBeijing 100083China institute of Exploration Technology Chinese Academy of Geological SciencesChengdu 611734China Chinese Academy of Geological Sciences China Geological SurveyBeijing 100037China institute of Geomechanics Chinese Academy of Geological SciencesChina Geological SurveyBeijing 100081China Geoscience Documentation Center China Geological SurveyMinistry of Natural ResourcesBeijing 100083China

The Hot Dry Rock(HDR)is considered as a clean and renewable energy,poised to significantly contribute to the global energy decarbonization *** HDR projects worldwide have accumulated valuable experience in efficient drilling and completion,reservoir construction,and fracture *** 2.19,China Geological Survey(CGS)initiated a demonstration project of HDR exploration and production in the Gonghe Basin,aiming to overcome the setbacks faced by HDR *** the ensuing four years,the Gonghe HDR project achieved the first power generation in 2.2.,followed by the second power generation test in *** establishing the primary well group in the initial phase,two directional wells and one branch well were *** progress was made in successfully constructing the targeted reservoir,realizing inter-well connectivity,power generation and grid connection,implementing of the real-time micro-seismic monitoring.A closed-loop technical validation of the HDR exploration and production was ***,many technical challenges remain in the process of HDR industrialization,such as reservoir fracture network characterization,efficient drilling and completion,multiple fracturing treatment,continuous injection and production,as well as mitigation of induced seismicity and numerical simulation technology.

关键词： Power generation Hot dry rock(HDR) Enhanced geothermal system(EGS) Genesis mechanism Gonghe Basin Directional drilling Reservoir construction Circulation test Induced seismicity Clean energy exploration engineering

Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma

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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi Su Kun Chen qing wu Jiayan Ren Wenjuan Tang Yu Hu Zeren Zhu Cheng Cheng Kaihui Tu Huaizhen He Yanmin zhang School of Pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 2. (SNAP2.)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma Sorafenib

The AaBBX2.–AaHY5 module mediates light-regulated artemisinin biosynthesis in Artemisia annua L.

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Journal of Integrative Plant Biology 2024年第8期66卷 1735-1751页

作者： Weizhi He Hang Liu zhangkuanyu wu qing Miao Xinyi Hu Xin Yan Hangyu Wen Yaojie zhang Xueqing Fu Li Ren Kexuan Tang Ling Li Frontiers Science Center for Transformative Molecules Joint International ResearchLaboratory of Metabolic and Developmental SciencesKey Laboratory of Urban Agriculture(South)Ministry of AgriculturePlant Biotechnology Research CenterFudan-SJTU-Nottingham Plant Biotechnology R&D CenterSchool of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China institute for Agri-Food Standards and Testing Technology Shanghai Academy of Agricultural SciencesShanghai 201403China

The sesquiterpene lactone artemisinin is an important anti-malarial component produced by the glandular secretory trichomes of sweet wormwood(Artemisia annua L.).Light was previously shown to promote artemisinin production,but the underlying regulatory mechanism remains *** this study,we demonstrate that ELONGATED HYPOCOTYL5(HY5),a central transcription factor in the light signaling pathway,cannot promote artemisinin biosynthesis on its own,as the binding of AaHY5 to the promoters of artemisinin biosynthetic genes failed to activate their *** analysis and yeast two-hybrid screening revealed the B-box transcription factor AaBBX2. as a potential interactor with ***2. showed a trichome-specific expression ***,the AaBBX2.–AaHY5 complex cooperatively activated transcription from the promoters of the downstream genes AaGSW1,AaMYB108,and AaORA,encoding positive regulators of artemisinin ***,AaHY5 and AaBBX2. physically interacted with the *** E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1(COP1).In the dark,AaCOP1 decreased the accumulation of AaHY5 and AaBBX2. and repressed the activation of genes downstream of the AaHY5–AaBBX2. complex,explaining the enhanced production of artemisinin upon light *** study provides insights into the central regulatory mechanism by which light governs terpenoid biosynthesis in the plant kingdom.

关键词： AaBBX2. AaHY5 AaCOP1 Artemisia annua L. artemisinin biosynthesis light

Pig H3K4me3,H3K2.ac,and gene expression profiles reveal reproductive tissue-specific activity of transposable elements

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Zoological Research 2024年第1期45卷 138-151页

作者： Tao Jiang Zhi-Min Zhou Zi-Qi Ling qing zhang Zhong-Zi wu Jia-Wen Yang Si-Yu Yang Bin Yang Lu-Sheng Huang National Key Laboratory of Pig Genetic Improvement and Germplasm Innovation Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Regulatory sequences and transposable elements(TEs)account for a large proportion of the genomic sequences of species;however,their roles in gene transcription,especially tissue-specific expression,remain largely *** serve as an excellent animal model for studying genomic sequence biology due to the extensive diversity among their wild and domesticated ***,we conducted an integrated analysis using H3K2.ac ChIP-seq,H3K4me3 ChIP-seq,and RNA-seq data from 10 different tissues of seven fetuses and eight closely related adult *** aimed to annotate the regulatory elements and TEs to elucidate their associations with histone modifications and mRNA expression across different tissues and developmental *** on correlation analysis between mRNA expression and H3K2.ac and H3K4me3 peak activity,results indicated that H3K2.ac exhibited stronger associations with gene expression than ***,1.45%of TEs overlapped with either the H3K2.ac or H3K4me3 peaks,with the majority displaying tissue-specific ***,a TE subfamily(LTR4C_SS),containing binding motifs for SIX1 and SIX4,showed specific enrichment in the H3K2.ac peaks of the adult and fetal ***-seq analysis also revealed widespread expression of TEs in the exons or promoters of genes,including 4688 TE-containing transcripts with distinct development stage-specific and tissue-specific *** note,1967 TE-containing transcripts were enriched in the *** identified a long terminal repeat(LTR),MLT1F1,acting as a testis-specific alternative promoter in SRPK2.a cell cycle-related protein kinase)in our pig *** element was also conserved in humans and mice,suggesting either an ancient integration of TEs in genes specifically expressed in the testes or parallel evolutionary ***,our findings demonstrate that TEs are deeply embedded in the genome and exhibit important tissue-specific biological functions,particularly in the reproductive

关键词： Transposable elements Porcine Histone modification Alternative promoter TE-containing transcript