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Promotion effect of FOXCUT as a microRNA sponge for miR-24-3p on progression in triple-negative breast cancer through the p38 MAPK signaling pathway

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Chinese Medical Journal 2024年第1期137卷 105-114页

作者： Xiafei Yu Fangze Qian xiaoqiang Zhang Yanhui Zhu gao He Junzhe Yang Xian Wu Yi Zhou Li Shen Xiaoyue Shi Hongfei Zhang Xiao’an Liu Department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

Background:Triple-negative breast cancer(TNBC)is a type of highly invasive breast cancer with a poor prognosis.According to new research,long noncoding RNAs(lncRNAs)play a significant role in the progression of cancer.Although the role of lncRNAs in breast cancer has been well reported,few studies have focused on TNBC.This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript(FOXCUT)in triple-negative breast cancer.Methods:Based on a bioinformatic analysis of the cancer genome atlas(TCGA)database,we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues,which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University.The functions of FOXCUT in proliferation,migration,and invasion were detected in vitro or in vivo.Luciferase assays and RNA immunoprecipitation(RIP)were performed to reveal that FOXCUT acted as a competitive endogenous RNA(ceRNA)for the microRNA miR-24-3p and consequently inhibited the degradation of p38.Results:lncRNA FOXCUT was markedly highly expressed in breast cancer,which was associated with poor prognosis in some cases.Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo.Mechanistically,FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38,which might act as an oncogene in breast cancer.Conclusion:Collectively,this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

关键词： Triple negative breast neoplasms RNA,long noncoding FOXCUT miR-24-3p p38 MAPK signaling pathway Disease progression

Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi Guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang xiaoqiang Tang Yongsheng Chang Yong gao State Key Laboratory of Traditional Chinese Medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina Department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine ShenzhenChina Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjingChina Department of Biochemistry and Molecular Biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin resistance.Yet the details of the underlying mechanisms are not fully understood.Here,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of NAFLD.Hepatic Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin resistance.Conversely,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic mice.Notably,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXR)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLRP3 inflammasome activity.This key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in macrophages.Altogether,Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression,which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

Orthogonal Combinatorial Raman Codes Enable Rapid High-Throughput-Out Library Screening of Cell-Targeting Ligands

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Research 2024年第1期2023卷 199-208页

作者： Yuchen Tang Xingxing Zheng Tingjuan gao China Key Laboratory of Pesticide and Chemical Biology of Ministry of Education College of ChemistryCentral China Normal UniversityWuhan 430079China

High-throughput assays play an important role in the fields of drug discovery,genetic analysis,and clinical diagnostics.Although super-capacity coding strategies may facilitate labeling and detecting large numbers of targets in a single assay,practically,the constructed large-capacity codes have to be decoded with complicated procedures or are lack of survivability under the required reaction conditions.This challenge results in either inaccurate or insufficient decoding outputs.Here,we identified chemical-resistant Raman compounds to build a combinatorial coding system for the high-throughput screening of cell-targeting ligands from a focused 8-mer cyclic peptide library.The accurate in situ decoding results proved the signal,synthetic,and functional orthogonality for this Raman coding strategy.The orthogonal Raman codes allowed for a rapid identification of 63 positive hits at one time,evidencing a high-throughput-out capability in the screening process.We anticipate this orthogonal Raman coding strategy being generalized to enable efficient high-throughput-out screening of more useful ligands for cell targeting and drug discovery.

关键词： enable throughput allowed

Thoughts on Pairing Assistance to Tibet for Promoting Agricultural High-quality Development in Southern Tibet from the Perspective of Agricultural Power

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Asian Agricultural Research 2024年第3期16卷 18-24页

作者： Zhiguo SUN Li gao Yuanpeng SUN Guangchao CAO Xinying ZHOU xiaoqiang LI Hubei University of Science and Technology Xianning 437100China Academy of Plateau Science and Sustainability of People s Government of Qinghai Province&Beijing Normal University Xining 810008China Institute of Vertebrate Paleontology and Paleoanthropology Chinese Academy of SciencesBeijing 100044China

In the new era,there is an urgent need to further promote pairing assistance to Tibet,promote the simultaneous construction of a strong agriculture in Tibet and the China's Mainland,and compose a Chinese-style modernization.Southern Tibet,located in the southeastern part of the Tibet Autonomous Region,includes Shannan City and Nyingchi City,is a region assisted by four provincial partners including Hubei Province.This paper introduces the agricultural environment in southern Tibet,studies its agricultural characteristics,and analyzes the main issues of its pairing assistance.Taking forging the strong consciousness of the Chinese national community as the main line,the paper explores strategies for promoting agricultural high-quality development in southern Tibet through pairing assistance to Tibet from the perspective of agricultural power,and proposes some strategies,such as inheriting agricultural cultural heritage,promoting the upgrading of modern seed industry,enhancing the characteristic advantages of highland barley(naked barley)and animal husbandry industries,and developing edible fungi and cold water fish industries.

关键词： Pairing assistance to Tibet Southern Tibet Shannan City Nyingchi City Agricultural high-quality development Agricultural power

Evolution of HIV/AIDS Prevention and Control Policies in China:A Grounded Theory Approach

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China CDC weekly 2024年第1期6卷 12-22页

作者： Huang Li Rui gao Chichen Zhang School of Public Health Southern Medical UniversityGuangzhou CityGuangdong ProvinceChina School of Health Management Southern Medical UniversityGuangzhou CityGuangdong ProvinceChina Key Laboratory of Philosophy and Social Sciences of Colleges and Universities in Guangdong Province for Collaborative Innovation of Health Management Policy and Precision Health Service Southern Medical UniversityGuangzhou CityGuangdong ProvinceChina Graduate School Xi’an Jiaotong-Liverpool UniversitySuzhou CityJiangsu ProvinceChina School of Political Science and Public Administration Soochow UniversitySuzhou CityJiangsu ProvinceChina

Objective:This study aims to provide a theoretical foundation for the development and practical application of human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)prevention and control policy systems in China by scrutinizing,analyzing,and synthesizing the evolution of Chinese policies in this domain.Methods:Utilizing grounded theory,we employed NVivo12 software to perform text content analysis,mining,and coding classification,along with visualization techniques,on policy texts sourced from Chinese government platforms,including the official website of China’s State Council.We considered four analytical dimensions—time,subject,type,and object.Results:The National Health Commission and the State Council emerged as the primary entities engaged in policymaking for HIV/AIDS in China.We identified four distinct stages in the evolution of these policies,culminating in a novel‘sun-shaped’HIV/AIDS prevention and control policy network model with an emphasis on‘knowledge,attitude,and practice’at its nucleus,which aligns with national conditions and societal progress.Furthermore,the focal groups of these policies have been dynamically refined and updated over time.Conclusions:Our findings introduce a‘sunshaped’HIV/AIDS prevention and control policy network model specific to China.We observed a conceptual policy shift towards prioritizing overall human health rather than confining the focus to disease treatment.Additionally,in light of China’s growing elderly population,the imperative to address HIV/AIDS prevention and control among older adults is an issue that warrants increased attention.

关键词： prevention HIV/AIDS policy

Thermal and mechanical behavior of casting copper alloy wheel during wheel and belt continuous casting process

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China Foundry 2024年第1期21卷 82-90页

作者： Kun gao Yan Peng School of Mechanical Engineering Yanshan UniversityQinhuangdao 066004HebeiChina

To investigate the thermal and mechanical behavior of casting wheel,a two-dimensional thermoelastic-plastic finite element model was used to predict the temperature,stress and distortion distribution of the casting wheel during the wheel and belt continuous casting process.The effects of grinding thickness and casting speed on the thermal and mechanical behaviors of the center of the hot face of the casting wheel were discussed in detail.In each rotation,the casting wheel passes through four different spray zones.The results show that the temperature distribution of the casting wheel in different spray zones is similar,the temperature of the hot face is the highest and the temperature reaches the peak in the spray zoneⅢ.The stress and distortion depend on the temperature distribution,and the maximum stress and distortion of the hot face are 358.2 MPa and 1.82 mm,respectively.The temperature at the center of the hot face decreases with increasing grinding thickness and increases with increasing casting speed.

关键词： casting wheel finite element model grinding thickness casting speed hot face spray zones

The late Early-Paleozoic granitic magmatism in Northwestern Fujian, China: constraints on intraplate orogeny in the South China block

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Acta Geochimica 2024年第1期43卷 134-149页

作者： WanLi gao ZongXiu Wang Institute of Geomechanics Chinese Academy of Geological ScienceBeijing 100081People’s Republic of China Key Laboratory of Paleomagnetism and Tectonic Reconstruction of Ministry of Natural Resources Beijing 100081People’s Republic of China

The Early Paleozoic tectono-thermal event was a significant orogenic activity during the Phanerozoic era,which had a profound impact on the early crust of the South China Block(SCB) and established the foundation for later tectonic activity.The Wuyi-Yunkai orogenic belt in Southeastern China was extensively exposed to Early Paleozoic magmatism,the genetic mechanism of which remains controversial.To shed light on this issue,detailed petrological,geochemical,and zircon U-Pb-Hf isotopic studies were carried out on two granitoids,namely the Yuntongshan pluton and the gaoqiao pluton,identified in the central Wuyishan.Zircon U-Pb chronology of the Yuntongshan and gaoqiao bodies yielded ages of437±4 Ma(MSWD=2.2) and 404±2 Ma(MSWD=12),respectively,indicating that they were emplaced during the Early Silurian and Early Devonian periods.These granitoids are primarily composed of biotite-granite and biotite-monzonitic-granites,with high concentrations of S_(i)O_(2)(73.59-75.91 wt%),K_(2)O+Na_(2)O(8.31-8.73wt%),and low contents of MgO,CaO,Cr,Ni.They are classified as high-K calc-alkaline and weakly metaluminous-strongly peraluminous S-type granites.These granitoids are enriched in light rare earth elements(LREEs) and large ion lithophile elements(LILEs) and depleted in heavy rare earth elements(HREEs) and high field strength elements(HFSEs) with arc affinity.The εHf(t) values of-3.3 to-15.4 with two-stage Hf model ages ranging from 2829 to 1644 Ma,combined with the presence of Neoproterozoic inherited zircons,suggest that the primary magma of these granitoids was derived from the partial melting of Neoproterozoic crust with a Paleoproterozoic crustal model age.These findings,combined with the spatio-temporal distribution of regional magmatism,reveal that the late Early-Paleozoic granitoids formed in the intraplate orogenic background originating from the subduction of the proto-Tethys Ocean and proto-Pacific Ocean around the margin of the east Gondwana supercontinent.

关键词： Late Early-Paleozoic Granites Intraplate orogeny Cathysian block Zircon U-Pb-Hf Isotopic composition

Nociceptors and Macrophages in Bacterial Meningitis:Partners in Crime?

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Neuroscience Bulletin 2024年第3期40卷 418-420页

作者： Fang gao Hongzhen Hu The Kimberly and Eric J.Waldman Department of Dermatology Icahn School of Medicine at Mount SinaiNew York NY10029USA The Nash Family Department of Neuroscience Icahn School of Medicine at Mount SinaiNew York NY10029USA The Mark Lebwohl Center for Neuroinfammation and Sensation Icahn School of Medicine at Mount SinaiNew York NY10029USA Friedman Brain Institute Icahn School of Medicine at Mount SinaiNew York NY10029USA

Bacterial meningitis is a serious and potentially life-threatening infection that affects the protective layers surrounding the brain and spinal cord,known as the meninges.Several types of bacteria,including Streptococcus pneumoniae,Neisseria meningitidis,and Haemophilus influenzae,can cause this condition.Certain populations,such as infants,children,immunocompromised adults,and the elderly,are particularly vulnerable to these pathogens.Symptoms of bacterial meningitis can manifest suddenly and may include high fever,severe and persistent headache,stiff neck,vomiting,sensitivity to light,and confusion or changes in mental state[1,2].Identifying these symptoms in infants can be more challenging and may lead to long-term disability or death[3].Despite the effectiveness of vaccines,it is crucial to understand how bacteria invade the brain and how our innate immune system responds to infection(Fig.1).

关键词： protective infection suddenly

On the core entropy of Newton maps

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Science China Mathematics 2024年第1期67卷 77-128页

作者： Yan gao Department of Mathematics Shenzhen UniversityShenzhen 518060China

In this paper,we define the core entropy for postcritically-finite Newton maps and study its continuity within this family.We show that the entropy function is not continuous in this family,which is different from the... 详细信息

关键词： core entropy extended Newton graph critical marking polynomial Newton map