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Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

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World Journal of Stem Cells 2024年第4期16卷 444-458页

作者： cheng-Jin ai ling-Juan Chen li-Xuan Guo Ya-Ping Wang Zi-Yi Zhao Department of Laboratory Medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Ophthalmology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Central Laboratory Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Traditional Chinese Medicine Regulating Metabolic Diseases Key Laboratory of Sichuan Province Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.aiM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

关键词： Leukemia stem cells Gossypol acetic acid Reactive oxygen species Mitochondrial dysfunction Interleukin 6/janus kinase 1/signal transducer and activator of transcription 3 signaling

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Classifying hepatitis B therapies with insights from covalently closed circular DNA dynamics

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Virologica Sinica 2024年第1期39卷 9-23页

作者： Jie-li Hu ai-Long Huang Key Laboratory of Molecular Biology on Infectious Diseases Ministry of EducationChongqing Medical UniversityChongqing400016China

The achievement of a functional cure for chronic hepatitis B(CHB)remains limited to a minority of patients treated with currently approved drugs.The primary objective in developing new anti-HBV drugs is to enhance the functional cure rates for CHB.A critical prerequisite for the functional cure of CHB is a substantial reduction,or even eradication of covalently closed circular DNA(cccDNA).Within this context,the changes in cccDNA levels during treatment become as a pivotal concern.We have previously analyzed the factors influencing cccDNA dynamics and introduced a preliminary classification of hepatitis B treatment strategies based on these dynamics.In this review,we employ a systems thinking perspective to elucidate the fundamental aspects of the HBV replication cycle and to rationalize the classification of treatment strategies according to their impact on the dynamic equilibrium of cccDNA.Building upon this foundation,we categorize current anti-HBV strategies into two distinct groups and advocate for their combined use to significantly reduce cccDNA levels within a well-defined timeframe.

关键词： Hepatitis B cccDNA Functional cure Dynamics Treatment Strategy

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Volume-averaged modeling of multiphase solidification with equiaxed crystal sedimentation in a steel ingot

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China Foundry 2024年第3期21卷 229-238页

作者： Xiao-lei Zhu Shuang Cao Rui Guan Ji Yang Zhe Ning Xin-gang ai Sheng-li li Xin-cheng Miao The key Laboratory of Material Forming and Structure Property Control Anshan 114051LiaoningChina State Key Laboratory of Metal Material for Marine Equipment and Application Anshan 114009LiaoningChina School of Materials and Metallurgy University of Science and Technology LiaoningAnshan 114051LiaoningChina

Macrosegregation is a critical factor that limits the mechanical properties of materials.The impact of equiaxed crystal sedimentation on macrosegregation has been extensively studied,as it plays a significant role in determining the distribution of alloying elements and impurities within a material.To improve macrosegregation in steel connecting shafts,a multiphase solidification model that couples melt flow,heat transfer,microstructure evolution,and solute transport was established based on the volume-averaged Eulerian-Eulerian approach.In this model,the effects of liquid phase,equiaxed crystals,columnar dendrites,and columnar-to-equiaxed transition(CET)during solidification and evolution of microstructure can be considered simultaneously.The sedimentation of equiaxed crystals contributes to negative macrosegregation,where regions between columnar dendrites and equiaxed crystals undergo significant A-type positive macrosegregation due to the CET.Additionally,noticeable positive macrosegregation occurs in the area of final solidification in the ingot.The improvement in macrosegregation is beneficial for enhancing the mechanical properties of connecting shafts.To mitigate the thermal convection of molten steel resulting from excessive superheating,reducing the superheating during casting without employing external fields or altering the design of the ingot mold is indeed an effective approach to control macrosegregation.

关键词： ingot casting multiphase solidification model equiaxed crystal sedimentation microstructure macrosegregation

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Recent progress in functional modification and crosslinking of bioprosthetic heart valves

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Regenerative Biomaterials 2024年第1期3卷 1-16页

作者： cheng Zheng li Yang Yunbing Wang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China

Valvular heart disease(VHD),clinically manifested as stenosis and regurgitation of native heart valve,is one of the most prevalent cardiovascular diseases with high mortality.Heart valve replacement surgery has been recognized as golden standard for the treatment of VHD.Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves(BHVs),implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD.However,BHVs might fail within 10-15 years due to structural valvular degeneration(SVD),which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs,including cytotoxicity,calcification,component degradation,mechanical failure,thrombosis and immune response.To prolong the service life of BHVs,much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD.In this review,we summarized and analyzed the research and progress on:(i)modification strategies based on glutaraldehyde crosslinked BHVs and(ii)nonglutaraldehyde crosslinking strategies for BHVs.

关键词： bioprosthetic heart valves modification crosslinking anticalcification antithrombosis

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Integration of urchin-like MnCo_(2)O_(4)@C core–shell nanowire arrays within porous copper current collector for superior performance li-ion battery anodes

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Rare Metals 2024年第2期43卷 599-611页

作者： Xue-Ru Zhang Qiong Wu Yong Zhang Xi-Fei li Ting Xie Yu-cheng Wu Instrumental Analysis Center Hefei University of TechnologyHefei230009China Key Laboratory of Advanced Functional Materials and Devices of Anhui Province Hefei230009China School of Materials Science and Engineering Hefei University of TechnologyHefei230009China Institute of Advanced Electrochemical Energy Xi’an University of TechnologyXi’an710048China

Spinel MnCo_(2)O_(4) is a promising energy storage candidate as anode materials in lithium-ion batteries owing to synergistic effects of two intrinsic solid-state redox couples.However,low conductivity,poor rate capacity and rapid capacity fading have seriously impaired its practical applications.To overcome the inferiorities,urchin-like MnCo_(2)O_(4)@C core–shell nanowire arrays have been fabricated directly within a porous copper current collector via a facile hydrothermal method followed by a chemical vapor deposition carbonization process.In a typical nanowire,the core is composed of interconnected MnCo_(2)O_(4)nanoparticles and the shell shows as a thin amorphous carbon layer.The integrated MnCo_(2)O_(4)@C/Cu structure could act as working anodes without using additives or polymer binders.While MnCo_(2)O_(4)@C/Cu possesses slightly longer li-ion insertion/desertion pathway than that of MnCo_(2)O_(4)/Cu,the carbon shell could effectively prevent the pulverization of MnCo_(2)O_(4) and lower down charge transfer resistance and actively participate in li-ion cycles.The rearrangement of carbon atoms during lithiation/delithiation cycling could inhibit the formation of passive solid electrolyte interphase films.As a result,the MnCo_(2)O_(4)@C/Cu electrode presents superior rate capacity(600 mAh·g^(−1) at 1 A·g^(−1)) and better stability(797 mAh·g^(−1) after 200 cycles at 100 mA·g^(−1)).The excellent reversible li ion storage capacity,cycling stability and rate capacity endow MnCo_(2)O_(4)@C/Cu great potential as stable and high output integrated anode materials in li-ion batteries.

关键词： MnCo_(2)O_(4)@C Urchin-like nanowire arrays Core-shell Integrated anode materials lithium-ion batteries

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Adaptive and augmented active anomaly detection on dynamic network traffic streams

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Frontiers of Information Technology & Electronic Engineering 2024年第3期25卷 446-460页

作者： Bin li Yijie WANG li cheng National Key Laboratory of Parallel and Distributed Computing College of ComputerNational University of Defense TechnologyChangsha 410073China College of System Engineering National University of Defense TechnologyChangsha 410073China

Active anomaly detection queries labels of sampled instances and uses them to incrementally update the detection model,and has been widely adopted in detecting network attacks.However,existing methods cannot achieve desirable performance on dynamic network traffic streams because(1)their query strategies cannot sample informative instances to make the detection model adapt to the evolving stream and(2)their model updating relies on limited query instances only and fails to leverage the enormous unlabeled instances on streams.To address these issues,we propose an active tree based model,adaptive and augmented active prior-knowledge forest(A3PF),for anomaly detection on network trafic streams.A prior-knowledge forest is constructed using prior knowledge of network attacks to find feature subspaces that better distinguish network anomalies from normal traffic.On one hand,to make the model adapt to the evolving stream,a novel adaptive query strategy is designed to sample informative instances from two aspects:the changes in dynamic data distribution and the uncertainty of anomalies.On the other hand,based on the similarity of instances in the neighborhood,we devise an augmented update method to generate pseudo labels for the unlabeled neighbors of query instances,which enables usage of the enormous unlabeled instances during model updating.Extensive experiments on two benchmarks,CIC-IDS2017 and UNSW-NB15,demonstrate that A3PF achieves significant improvements over previous active methods in terms of the area under the receiver operating characteristic curve(AUC-ROC)(20.9%and 21.5%)and the area under the precision-recall curve(AUC-PR)(44.6%and 64.1%).

关键词： Active anomaly detection Network traffic streams Pseudo labels Prior knowledge of network attacks

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Prediction of cell-cell communication patierns of dorsal root ganglion cells: single-cell RNA sequencing data analysis

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Neural Regeneration Research 2024年第6期19卷 1367-1374页

作者： Yanna lian cheng Wu li liu Xiangyao li National Health Commission and Chinese Academy of Medical Sciences Key Laboratory of Medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine Integration School of Brain Science and Brain Medicine Zhejiang University International Institutes of Medicine the Fourth Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University-University of Edinburgh Institute Zhejiang University School of Medicine Zhejiang University 4. Biomedical Sciences College of Medicine and Veterinary Medicine The University of Edinburgh Core Facilities of the School of Medicine Zhejiang University

Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system, and dorsal root ganglion neuron excitability affects pain perception. Dorsal root ganglion stimulation is a new approach for managing pain sensation. Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies. Here, we used the single-cell RNA-sequencing(scRNA-seq) database to investigate intercellular communication networks among dorsal root ganglion cells. We collected scRNA-seq data from six samples from three studies, yielding data on a total of 17,766 cells. Based on genetic profiles, we identified satellite glial cells, Schwann cells, neurons, vascular endothelial cells, immune cells, fibroblasts, and vascular smooth muscle cells. Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive, itch, touch, mechanical, heat, and cold sensations. Moreover, we predicted several distinct forms of intercellular communication among dorsal root ganglion cells, including cell-cell contact, secreted signals, extracellular matrix, and neurotransmitter-mediated signals. The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b(A2B) receptor and glial cell line-derived neurotrophic factor family receptor alpha 1(GFRα-1). Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1. Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner. Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation. Furthermore, our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms. Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

关键词： cell-cell communications CellChat dorsal root ganglion scRNA-Seq database

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Combining genome-wide association study and transcriptome analysis to identify molecular markers and genetic basis of population-asynchronous ovarian development in Coilia nasus

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Zoological Research 2024年第3期45卷 491-505页

作者： Yue Yu Shi-Ming Wan cheng-You Huang Shuang-Meng Zhang ai-li Sun Jun-Qi liu Shun-Yao li Yong-Fu Zhu Shu-Xin Gu Ze-Xia Gao College of Fisheries Hubei Hongshan Laboratory/Key Lab of Freshwater Animal BreedingMinistry of Agriculture and Rural Affairs/Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic BeltMinistry of EducationHuazhong Agricultural UniversityWuhanHubei 430070China Laboratory for Marine Biology and Biotechnology Qingdao Marine Science and Technology CenterQingdaoShandong 266237China Wuhan Hengyuxin Technology Breeding Professional Cooperative WuhanHubei 430117China Hubei Provincial Aquatic Science Research Institute WuhanHubei 430208China Zhenjiang Jiangzhiyuan Fishery Technology Co. Ltd.ZhenjiangJiangsu 212213China

Coilia nasus,a migratory fish species found in the middle and lower reaches of the Yangtze River and along offshore areas of China,possesses considerable aquacultural and economic potential.However,the species faces challenges due to significant variation in the gonadal development rate among females,resulting in inconsistent ovarian maturation times at the population level,an extended reproductive period,and limitations on fish growth rate due to ovarian prematurity.In the present study,we combined genome-wide association study(GWAS)and comparative transcriptome analysis to investigate the potential single nucleotide polymorphisms(SNPs)and candidate genes associated with population-asynchronous ovarian development in C.nasus.Genotyping of the female population based on whole-genome resequencing yielded 2120695 high-quality SNPs,39 of which were suggestively associated with ovarian development.Of note,a significant SNP peak on LG21 containing 30 suggestively associated SNPs was identified,with cpne5a determined as the causal gene of the peak.Therefore,single-marker and haplotype association analyses were performed on cpne5a,revealing four genetic markers(P0.9)significantly associated with the phenotype.Comparative transcriptome analysis of precociously and normally maturing individuals screened out 29 and 426 overlapping differentially expressed genes in the brain and ovary,respectively,between individuals of different body sizes.Integrating the GWAS and transcriptome analysis results,this study identified genes and pathways related to hypothalamic-pituitary-gonadal axis hormone secretion,extracellular matrix,angiogenesis,and gap junctions involved in population-asynchronous ovarian development.The insights gained from this study provide a basis for a deeper understanding of the molecular mechanisms underlying ovarian development in fish and may facilitate the genetic breeding of C.nasus strains exhibiting population-synchronous ovarian development in the future.

关键词： Coilia nasus GWAS Transcriptome Ovarian development SNP

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Complex-frequency waves:beat loss and win sensitivity

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light(Science & Applications) 2024年第2期13卷 181-183页

作者： Qingqing cheng Tao L School of Optical-Electrical and Computer Engineering University of Shanghai for Science and TechnologyShanghai200093China Department of Respiratory Diseases and Critical Medicine Quzhou Hospital Affiliated to Wenzhou Medical UniversityQuzhou324000China National Laboratory of Solid State Microstructures College of Engineering and Applied SciencesNanjing UniversityNanjing210093China

Recent experiments have demonstrated that synthesized complex-frequency waves can impart a virtual gain to molecule sensing systems,which can effectively restore information lost due to intrinsic molecular damping.The enhancement notably amplifies the signal of trace molecular vibrational fingerprints,thereby substantially improving the upper limit of sensitivity.

关键词： thereby Complex limit

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Current status of early gastric cancer screening research

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Cancer Biology & Medicine 2024年第3期21卷 218-222页

作者： Can Hu li Yuan Xiangdong cheng Department of Gastric surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiang 310022China Key Laboratory of Prevention Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang ProvinceHangzhou 310022China Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer Zhejiang Cancer HospitalHangzhou 310022China

Gastric cancer is a predominant threat to the health and well-being of China's residents. Data from the World Health Organization(WHO) in 2020 revealed that gastric cancer in China notably accounted for 44.0% of new c... 详细信息

关键词： cancer Gastric gastric

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