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Black holes as the source of dark energy:A stringent test with high-redshift JWST AGNs

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Science China(Physics,Mechanics & Astronomy) 2024年第2期67卷 181-188页

作者： lei lei lei Zu Guan-Wen Yuan Zhao-Qiang Shen Yi-Ying Wang Yuan-Zhu Wang Zhen-Bo Su Wen-Ke Ren Shao-Peng Tang Hao Zhou Chi Zhang Zhi-Ping Jin lei Feng Yi-Zhong Fan Da-Ming Wei Key Laboratory of Dark Matter and Space Astronomy Purple Mountain ObservatoryChinese Academy of SciencesNanjing 210023China School of Astronomy and Space Science University of Science and Technology of ChinaHefei 230026China CAS Key Laboratory for Research in Galaxies and Cosmology Department of AstronomyUniversity of Science and Technology of ChinaHefei 230026China

Studies have proposed that there is evidence for cosmological coupling of black holes(BHs)with an index of k≈3;hence,BHs serve as the astrophysical source of dark energy.However,the data sample is limited for the redshifts of≤2.5.In recent years,the James Webb Space Telescope(JWST)has detected many high-redshift active galactic nuclei(AGNs)and quasars.Among the JWST NIRSpec-/NIRCam-resolved AGNs,three are determined to be in early-type host galaxies with a redshift of z~4.5-7.However,their M_(*)and MBH are in tension with the predicted cosmological coupling of black holes with k=3 at a confidence level of~2σ,which challenges the hypothesis that BHs serve as the origin of dark energy.Future work on high-redshift AGNs using the JWST will further assess such a hypothesis by identifying more early-type host galaxies in the higher mass range.

关键词： dark energy supermassive black hole active galactic nuclei James Webb Space Telescope

Sorafenib plus transarterial chemoembolization vs sorafenib alone for patients with advanced hepatocellular carcinoma: A systematic review and meta-analysis

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World Journal of Hepatology 2024年第1期16卷 91-102页

作者： Hong-Jie Yang Bin Ye Jia-Xu Liao lei lei Kai Chen Department of Radiology The Sixth People's Hospital of ChengduChengdu 610000Sichuan ProvinceChina Department of Oncology The Sixth People's Hospital of ChengduChengdu 610000Sichuan ProvinceChina Department of Pharmacy The Affiliated Taizhou People's Hospital of Nanjing Medical UniversityTaizhou 225300Jiangsu ProvinceChina

BACKGROUND Although the past decade has seen remarkable advances in treatment options for hepatocellular carcinoma(HCC),the dismal overall prognosis still envelops HCC patients.Several comparative trials have been conducted to study whether transarterial chemoembolization(TACE)could improve clinical outcomes in patients receiving sorafenib for advanced HCC;however,the findings have been inconsistent.AIM To study the potential synergies and safety of sorafenib plus TACE vs sorafenib alone for treating advanced HCC,by performing a systematic review and metaanalysis.METHODS This study was conducted following the PRISMA statement.A systematic literature search was conducted using the Cochrane Library,Embase,PubMed,and Web of Science databases.Data included in the present work were collected from patients diagnosed with advanced HCC receiving sorafenib plus TACE or sorafenib alone.Data synthesis and meta-analysis were conducted using Review Manager software.RESULTS The present study included 2780 patients from five comparative clinical trials(1 was randomized control trial and 4 were retrospective studies).It was found that patients receiving sorafenib plus TACE had better prognoses in terms of overall survival(OS),with a combined hazard ratio(HR)of 0.65[95%confidence interval(95%CI):0.46–0.93,P=0.02,n=2780].Consistently,progression free survival(PFS)and time to progression(TTP)differed significantly between the sorafenib plus TACE arm and sorafenib arm(PFS:HR=0.62,95%CI:0.40–0.96,P=0.03,n=443;TTP:HR=0.73,95%CI:0.64-0.83,P<0.00001,n=2451).Disease control rate(DCR)was also significantly increased by combination therapy(risk ratio=1.36,95%CI:1.02-1.81,P=0.04,n=641).Regarding safety,the incidence of any adverse event(AE)was increased due to the addition of TACE;however,no significant difference was found in grade≥3 AEs.CONCLUSION The combination of sorafenib with TACE has superior efficacy to sorafenib monotherapy,as evidenced by prolonged OS,PFS,and TTP,as well as increased DCR.Additional high-quality trials are essenti

关键词： Hepatocellular carcinoma Sorafenib Transarterial chemoembolization Systematic review Meta-analysis

Combination losartan with hyaluronic acid modified diethyldithiocarbamate loaded hollow copper sulfide nanoparticles for the treatment of breast cancer and metastasis

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Chinese Chemical Letters 2024年第3期35卷 406-414页

作者： Haili Hu Weiwei Zhang lei lei Fan Tong Huilin Zhang Yiwei Zhang Wenqin Yang Yilu Tang Ruyi Lin Xue Xia Jiamei Li Shiyong Song Huile Gao Key Laboratory of Drug Targeting and Drug Delivery Systems West China School of PharmacySichuan UniversityChengdu 610041China School of Pharmacy Henan UniversityKaifeng 475004China Department of Public Health Chengdu Medical CollegeChengdu 610500China

The application of photothermal therapy(PTT)is greatly limited by the low accumulation of photothermal agents,uneven photothermal distribution,and heat endurance of cancer cells.Worse still,despite PTT enhances immunogenicity,the anti-tumor immune efficacy is still unsatisfactory due to the inefficient immunogenic cell death(ICD)induction and poor infiltration of immune cells.To solve the above problems of PTT,we developed hyaluronic acid(HA)modified hollow copper sulfide nanoparticles encapsulating diethyldithiocarbamate(DDTC)to construct a breast tumor targeting and near infrared(NIR)photo-responsive drug delivery system(D-HCuS@HA),which further combined with losartan to improve the accumulation and penetration in the tumor site.Upon irradiation,D-HCuS@HA realized enhanced PTT and released cytotoxic Cu(DDTC)_(2)to eliminate heat endurance tumor cells,thereby enhancing antitumor effect and inducing effective ICD.Moreover,the combination with losartan could remodel the tumor microenvironment,allowing more T cells to infiltrate into the tumor,and significantly inhibiting the occurrence and development of metastatic tumors.In vitro/vivo results revealed the great potential of D-HCuS@HA combined with losartan,which provides a new paradigm for anti-tumor and anti-metastases.

关键词： Targeted drug delivery system Hollow copper sulfide nanoparticles Photothermal therapy Hyaluronic acid Breast cancer Anti-metastasis

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed–1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2567-2580页

作者： Hongying Li Jianrui Li Jiayu Li Hu Li Xuekai Wang Jing Jiang lei lei Han Sun Mei Tang Biao Dong Weiqing He Shuyi Si Bin Hong Yinghong Li Danqing Song Zonggen Peng Yongsheng Che Jian-Dong Jiang CAMS Key Laboratory of Antiviral Drug Research Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Key Laboratory of Biotechnology of Antibiotics the National Health and Family Planning Commission(NHFPC)Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials,decreases the efficiency of programmed–1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion.Carrimycin binds directly to the coronaviral frameshift-stimulatory element(FSE)RNA pseudoknot,interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes.Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses.Because the FSE mechanism is essential in all coronaviruses,carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA.This finding may open a new direction in antiviral drug discovery for coronavirus variants.

关键词： Carrimycin Coronavirus Broad-spectrum antiviral activity Programmed-1 ribosomal frameshifting RNA pseudoknot Antiviral agent RNA target Synergistic inhibitory effect

Rapidly growing primordial black holes as seeds of the massive high-redshift JWST Galaxies

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Science China(Physics,Mechanics & Astronomy) 2024年

作者： Guan-Wen Yuan lei lei Yuan-Zhu Wang Bo Wang Yi-Ying Wang Chao Chen Zhao-Qiang Shen Yi-Fu Cai Yi-Zhong Fan Key Laboratory of Dark Matter and Space Astronomy Purple Mountain ObservatoryChinese Academy of Sciences School of Astronomy and Space Science University of Science and Technology of China Institute of High Energy Physics Chinese Academy of Sciences Deep Space Exploration Laboratory/Department of Astronomy School of Physical SciencesUniversity of Science and Technology of China Jockey Club Institute for Advanced Study The Hong Kong University of Science and Technology

A group of massive galaxies at redshifts of z 7 have been recently detected by the James Webb Space Telescope (JWST),which were unexpected to form at such an early time within the standard Big Bang cosmology.In this work,we propose that this puzzle can be explained by the presence of some primordial black holes (PBHs) with a mass of～1000M⊙.These PBHs act as seeds for early galaxy formation with masses of～108-1010M⊙at high redshift,hence accounting for the JWST observations.We use a hierarchical Bayesian inference framework to constrain the PBH mass distribution models,and find that the Lognormal model with the Mc～750M⊙is preferred over other hypotheses.These rapidly growing BHs are expected to have strong radiation and may appear as high-redshift compact objects,similar to those recently discovered by JWST.Although we focused on PBHs in this work,the bound on the initial mass of the seed black holes remains robust even if they were formed through astrophysical channels.

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NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1421-1436页

作者： Yu-Jie Xu Ya-Chang Huo Qi-Tai Zhao Jin-Yan Liu Yi-Jun Tian lei-lei Yang Yi Zhang Biotherapy Center and Cancer Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Oncology Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityPeople’s Hospital of Henan UniversityZhengzhou 450003Henan ProvinceChina

BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.AIM To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of CRC.METHODS We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Consensus clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic genes.Sphere formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC.mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells.In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth.RESULTS We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes.Among these genes,NOX4 was highly expressed in tumor tissues and correlated with worse survival.In vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC cells.Furthermore,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway.Trametinib,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor progression.In vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the metastasis.CONCLUSION Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

关键词： Colorectal cancer Metabolic reprogramming Metastasis Nicotinamide adenine dinucleotide phosphate oxidase 4 Mitogen-activated protein kinase signaling

Inter-stage performance and energy characteristics analysis of electric submersible pump based on entropy production theory

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Petroleum Science 2024年第2期21卷 1354-1368页

作者： Hui Wang Yang Yang Bin Xi Wei-Dong Shi Chuan Wang lei-lei Ji Xiang-Yu Song Zhao-Ming He College of Hydraulic Science and Engineering Yangzhou UniversityYangzhou225009JiangsuChina College of Electrical and Mechanical Engineering Nanchang Institute of TechnologyNanchang330044JiangxiChina College of Mechanical Engineering Nantong UniversityNantong226019JiangsuChina National Research Center of Pumps Jiangsu UniversityZhenjiang212013JiangsuChina Zhejiang Zhenxing Petrochemical Machinery Co. Ltd.Ruian325204ZhejiangChina Department of Mechanical Engineering of Texas Tech University Lubbock79411TXUSA

The electric submersible pump(ESP) is a crucial apparatus utilized for lifting in the oil extraction process.Its lifting capacity is enhanced by the multi-stage tandem structure, but variations in energy characteristics and internal flow across stages are also introduced. In this study, the inter-stage variability of energy characteristics in ESP hydraulic systems is investigated through entropy production(EP) analysis,which incorporates numerical simulations and experimental validation. The EP theory facilitates the quantification of energy loss in each computational subdomain at all ESP stages, establishing a correlation between microscopic flow structure and energy dissipation within the system. Furthermore, the underlying causes of inter-stage variability in ESP hydraulic systems are examined, and the advantages and disadvantages of applying the EP theory in this context are evaluated. Consistent energy characteristics within the ESP, aligned with the distribution of internal flow structure, are provided by the EP theory, as demonstrated by our results. The EP theory also enables the quantitative analysis of internal flow losses and complements existing performance analysis methods to map the internal flow structure to hydraulic losses. Nonetheless, an inconsistency between the energy characterization based on EP theory and the traditional efficiency index when reflecting inter-stage differences is identified. This inconsistency arises from the exclusive focus of the EP theory on flow losses within the flow field, disregarding the quantification of external energy input to the flow field. This study provides a reference for the optimization of EP theory in rotating machinery while deeply investigating the energy dissipation characteristics of multistage hydraulic system, which has certain theoretical and practical significance.

关键词： Electric submersible pump(ESP) Entropy production theory Energy characteristics Inter-stage differences

The nanohertz stochastic gravitational wave background from cosmic string loops and the abundant high redshift massive galaxies

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Science China(Physics,Mechanics & Astronomy) 2023年第12期66卷 11-19页

作者： Ziwei Wang lei lei Hao Jiao lei Feng Yi-Zhong Fan Key Laboratory of Dark Matter and Space Astronomy Purple Mountain ObservatoryChinese Academy of SciencesNanjing 210023China School of Astronomy and Space Science University of Science and Technology of ChinaHefei 230026China Department of Physics McGill UniversityMontreal H3A 2T8Canada

Recently,pulsar timing array(PTA)experiments have provided compelling evidence for the existence of the nanohertz stochastic gravitational wave background(SGWB).In this work,we demonstrated that cosmic string loops generated from cosmic global strings offer a viable explanation for the observed nanohertz SGWB data,requiring a cosmic string tension parameter of log(Gμ)~-12 and a loop number density of log N~4.Additionally,we revisited the impact of cosmic string loops on the abundance of massive galaxies at high redshifts.However,our analysis revealed challenges in identifying a consistent parameter space that can concurrently explain both the SGWB data and observations from the James Webb Space Telescope.This indicates the necessity for either extending the existing model employed in this research or acknowledging distinct physical origins for these two phenomena.

关键词： nanohertz stochastic gravitational-wave background cosmic string loop JamesWebb Space Telescope galaxy formation

Influence of two polyphenols on the structure and lubrication of salivary pellicle:An in vitro study on astringency mechanism

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Friction 2022年第1期10卷 167-178页

作者： lei lei Yue TANG Jing ZHENG Genlei MA Zhongrong ZHOU Tribology Research Institute Key Laboratory of Advanced Technologies of MaterialsMinistry of EducationSouthwest Jiaotong UniversityChengdu 610031China

This study investigated the influence of two polyphenols on the structure and lubrication of the salivary pellicle,aiming to extend the understanding of astringency mechanisms.The salivary pellicle was prepared by the adsorption of human whole saliva on the enamel substrate.Low-astringency catechin and high-astringency tannic acid were used as astringents.The changes induced by the two polyphenols in the structure and lubrication of the salivary pellicle were examined using quartz crystal microbalance with dissipation(QCM-D)and nano-indentation/scratch technique.The salivary pellicle suffers from changes in structure and physical properties owing to protein dehydration and protein-polyphenol complexation when encountering polyphenolic molecules,causing increases in the roughness and contact angle but a decrease in the load-bearing capacity.Therefore,the lubrication performance of the salivary pellicle is impaired,leading to an increase and fluctuation of the friction coefficient.The intensity of astringency has a strong positive correlation with the water contact angle,surface roughness,and friction coefficient of the salivary pellicle.In summary,astringency is a tactile perception driven by the roughness and wettability of the salivary pellicle rather than oral lubrication,and increased intraoral friction is an inevitable consequence of astringency.The findings of this study will help promote and assist the objective evaluation of astringency.

关键词： salivary impaired string