Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containin...Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.展开更多
Extensive research attentions have been devoted to studying cooperative cognitive radio networks(CCRNs),where secondary users(SU)providing cooperative transmissions can be permitted by primary users(PU)to use spectrum...Extensive research attentions have been devoted to studying cooperative cognitive radio networks(CCRNs),where secondary users(SU)providing cooperative transmissions can be permitted by primary users(PU)to use spectrum.In order to maximize SU’s utility,SU may transmit its own information during the period of cooperative transmission,which stimulates the use of covert transmission against PU’s monitoring.For this sake,this article reviews the motivations of studying covert communications in CCRN.In particular,three intelligent covert transmission approaches are developed for maximizing SU’s utility in CCRNs,namely,intelligent parasitic covert transmission(IPCT),intelligent jammer aided covert transmission(IJCT)and intelligent reflecting surface assisted covert transmission(IRSC).Further,some raw performance evaluations are discussed,and a range of potential research directions are also provided.展开更多
The accuracy of laser-induced breakdown spectroscopy(LIBS) quantitative method is greatly dependent on the amount of certified standard samples used for training. However, in practical applications, only limited stand...The accuracy of laser-induced breakdown spectroscopy(LIBS) quantitative method is greatly dependent on the amount of certified standard samples used for training. However, in practical applications, only limited standard samples with labeled certified concentrations are available. A novel semi-supervised LIBS quantitative analysis method is proposed, based on co-training regression model with selection of effective unlabeled samples. The main idea of the proposed method is to obtain better regression performance by adding effective unlabeled samples in semisupervised learning. First, effective unlabeled samples are selected according to the testing samples by Euclidean metric. Two original regression models based on least squares support vector machine with different parameters are trained by the labeled samples separately, and then the effective unlabeled samples predicted by the two models are used to enlarge the training dataset based on labeling confidence estimation. The final predictions of the proposed method on the testing samples will be determined by weighted combinations of the predictions of two updated regression models. Chromium concentration analysis experiments of 23 certified standard high-alloy steel samples were carried out, in which 5 samples with labeled concentrations and 11 unlabeled samples were used to train the regression models and the remaining 7 samples were used for testing. With the numbers of effective unlabeled samples increasing, the root mean square error of the proposed method went down from 1.80% to 0.84% and the relative prediction error was reduced from 9.15% to 4.04%.展开更多
Myc belongs to a family of proto-oncogenes that encode transcription factors.The overexpression of c-Myc causes many types of cancers.Recently,we established a system for screening c-Myc inhibitors and identified anti...Myc belongs to a family of proto-oncogenes that encode transcription factors.The overexpression of c-Myc causes many types of cancers.Recently,we established a system for screening c-Myc inhibitors and identified antimycin A by screening the RIKEN NPDepo chemical library.The specific mechanism of promoting tumor cell metastasis by high c-Myc expression remains to be explained.In this study,we screened approximately 5,600 microbial extracts using this system and identified a broth prepared from Streptomyces sp.RK19-A0402 strongly inhibits c-Myc transcriptional activity.After purification of the hit broth,we identified compounds closely related to the aglycone of cytovaricin and had a structure similar to that of oligomycin A.Similar to oligomycin A,the hit compounds inhibited mitochondrial complex V.The mitochondria dysfunction caused by the compounds induced the production of reactive oxygen species(ROS),and the ROS activated GSK3α/βthat phosphorylated c-Myc for ubiquitination.This study provides a successful screening strategy for identifying natural products as potential c-Myc inhibitors as potential anticancer agents.展开更多
Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Th...Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.展开更多
The biosecurity hazards caused by pathogenic fungus have been widely concerned.Given the long-term coexistence of eukaryotic pathogens and quorum sensing bacteria in different habitats in environments,we hypothesized ...The biosecurity hazards caused by pathogenic fungus have been widely concerned.Given the long-term coexistence of eukaryotic pathogens and quorum sensing bacteria in different habitats in environments,we hypothesized that they have social interactions via signal molecules.In this work,we firstly discovered the well-known bacterial signal molecules play an adverse role in the cell morphology and metabolism in a model pathogen Trichosporon asahii.N-Tetradecanoyl-L-homoserine lactone(C14-HSL)was discovered to increase pathogen hazards of T.asahii,which limited mycelium by 52%,but enhanced cell aggregation by 93%.Higher fluorescence intensity of tryptophan(59%)and aromatic protein(2-fold)contents after the treatment of C14-HSL,indicating that aromatic proteins helped aggregate Trichosporon and showed hydrophobicity.Transcriptome analysis revealed that C14-HSL upregulated the shikimate pathway(above1-fold)located in downstream of tricarboxylic acid cycle,which contributed to the synthesis of more aromatic proteins and the formation of larger flocs.The limited mycelial growth of T.asahii attributed to the up-regulated expressions of cell cycle process.The fungal transboundary response to bacterial C14-HSL was controlled by signal transduction pathways.This study provides new insights into the co-evolution of bacterial and pathogenic fungi in microecosystems.展开更多
β-transducin repeat-containing protein(β-TrCP)is an F-box protein subunit of the E3 Skp1-Cullin-F box(SCF)type ubiquitin-ligase complex,and provides the substrate specificity for the ligase.To find potent ligands of...β-transducin repeat-containing protein(β-TrCP)is an F-box protein subunit of the E3 Skp1-Cullin-F box(SCF)type ubiquitin-ligase complex,and provides the substrate specificity for the ligase.To find potent ligands ofβ-TrCP useful for the proteolysis targeting chimera(PROTAC)system usingβ-TrCP in the future,we developed a high-throughput screening system for small moleculeβ-TrCP ligands.We screened the chemical library utilizing the system and obtained several hit compounds.The effects of the hit compounds on in vitro ubiquitination activity of SCFβ-TrCP1 and on downstream signaling pathways were examined.Hit compounds NPD5943,NPL62020-01,and NPL42040-01 inhibited the TNFα-induced degradation of IκBαand its phosphorylated form.Hence,they inhibited the activation of the transcription activity of NF-κB,indicating the effective inhibition ofβ-TrCP by the hit compounds in cells.Next,we performed an in silico analysis of the hit compounds to determine the important moieties of the hit compounds.Carboxyl groups of NPL62020-01 and NPL42040-01 and hydroxyl groups of NPD5943 created hydrogen bonds withβ-TrCP similar to those created by intrinsic target phosphopeptides ofβ-TrCP.Our findings enhance our knowledge of useful small molecule ligands ofβ-TrCP and the importance of residues that can be ligands ofβ-TrCP.展开更多
Background:Alzheimer's disease(AD)and lung cancer are leading causes of mortality among the older population.Epidemiological evidence suggests an antagonistic relationship between them,whereby patients with AD exh...Background:Alzheimer's disease(AD)and lung cancer are leading causes of mortality among the older population.Epidemiological evidence suggests an antagonistic relationship between them,whereby patients with AD exhibit a reduced risk of developing cancer and vice versa.However,the precise mechanism by which AD antagonizes lung cancer progression warrants further elucidation.Methods:To this end,we established a co-morbidity model using 5xFAD transgenic mice induced with the carcinogen urethane.We visualized and quantified surface lung tumor colonies,assessed pathological parameters associated with lung cancer and AD using histopathological analysis,and employed single-cell sequencing and molecular pathological analyses to explore the mechanisms by which AD confers resistance to lung cancer.Results:Our findings revealed a significant reduction in lung tumor incidence in the AD group compared with that in the wild-type(WT)group.The results indicated a close association between AD-induced inhibition of lung tumor progression and iron homeostasis imbalance and increased oxidative stress.Moreover,greater CD8^(+)T cytotoxic lymphocyte and effector natural killer cell infiltration in the lung tumor tissues of AD mice and enhanced CD8^(+)T cytotoxic lymphocyte-mediated killing of target cells may be the primary factors contributing to the inhibition of lung tumor growth in the presence of AD.Conclusion:This study identified essential mechanisms through which AD suppresses lung tumorigenesis,thereby providing targets for potential therapeutic interventions in these diseases.展开更多
开花时间对植物的繁殖成功至关重要。广泛分布的物种经常发生开花时间的分化,从而能够更好地适应不同的环境条件。为了探索植物开花行为发生适应性分化的分子机制,首先要明确调控开花行为的遗传通路。本文梳理了植物各类群调控开花时间...开花时间对植物的繁殖成功至关重要。广泛分布的物种经常发生开花时间的分化,从而能够更好地适应不同的环境条件。为了探索植物开花行为发生适应性分化的分子机制,首先要明确调控开花行为的遗传通路。本文梳理了植物各类群调控开花时间的遗传通路,以期为开花时间适应性分化的分子机制研究提供依据。植物从营养生长向繁殖转变时,其开花行为主要受到光照、温度、水分等外界环境因子和赤霉素等内在因素的影响。通过对模式植物拟南芥(Arabidopsis thaliana)和其他类群的研究,总结出了调控植物开花时间的6条通路,包括日照长度和光质影响开花的光依赖通路,长时间冷暴露后促进植物开花的春化通路,高温或低温环境影响开花的温度通路,以及赤霉素通路、年龄通路和自主通路3条内部调节过程。植物开花时间调控的6条上游通路信号传递到下游的开花整合基因FT(FLOWERING LOCUS T)和SOC1(SUPPRESSOR OF OVER-EXPRESSION OF CONSTANS 1),整合基因将这些复杂的调节因子整合后进一步传递到下游花分生组织,从而启动开花。此外,非编码RNA、转座子对开花时间的调控也具有重要作用。部分遗传通路被证实在植物适应环境的过程中起到了重要作用。目前对植物开花调控的研究已经有一百多年历史,理论相对成熟。然而,仍然存在许多具有争议和未解决的问题,如开花基因的表达方式、开花行为的特殊调控机制、开花时间变异的适应性意义等等,需要更进一步的研究。展开更多
Collective cells are organized to form specific patterns which play important roles in various physiological and pathological processes,such as tissue morphogenesis,wound healing,and cancer invasion.Compared to single...Collective cells are organized to form specific patterns which play important roles in various physiological and pathological processes,such as tissue morphogenesis,wound healing,and cancer invasion.Compared to single cell behaviors,which has been intensively studied from many aspects(cell migration,adhesion,polarization,proliferation,etc.)and at various scales(molecular,subcellular,and cellular),the multiple cell behaviors are relatively less understood,particularly in a quantitative manner.In this paper,we will present our recent studies of collective polarization and orientation of multiple cells through both experimental measurement and theoretical modeling,including those cell behaviors on/in 2D and 3D substrate/tissue.We find that the collective cell behaviors,including polarization,alignment and migration are closely related to local stress states in cell layer or tissue,which demonstrate the crucial roles of mechanical forces in the living organisms.Specifically,the cells prefer to polarize and align along the maximum principal stress in the cell layer,and the aspect ratio of cell increases with the in-plane maximum shear stress,suggesting that the maximum shear stress is the underlying driving force of cell polarization and orientation.This theory of stress-driven cell behaviors of polarization and orientation provides a new perspective for understanding cell behaviors in living organisms and the guideline for tissue engineering in biomedical applications.展开更多
The prolonged mei-yu/baiu system with anomalous precipitation in the year 2020 has swollen many rivers and lakes,caused flash flooding,urban flooding and landslides,and consistently wreaked havoc across large swathes ...The prolonged mei-yu/baiu system with anomalous precipitation in the year 2020 has swollen many rivers and lakes,caused flash flooding,urban flooding and landslides,and consistently wreaked havoc across large swathes of China,particularly in the Yangtze River basin.Significant precipitation and flooding anomalies have already been seen in magnitude and extension so far this year,which have been exerting much higher pressure on emergency responses in flood control and mitigation than in other years,even though a rainy season with multiple ongoing serious flood events in different provinces is not that uncommon in China.Instead of delving into the causes of the uniqueness of this year’s extreme precipitation-flooding situation,which certainly warrants in-depth exploration,in this article we provide a short view toward a more general hydrometeorological solution to this annual nationwide problem.A“glocal”(global to local)hydrometeorological solution for floods(GHS-F)is considered to be critical for better preparedness,mitigation,and management of different types of significant precipitation-caused flooding,which happen extensively almost every year in many countries such as China,India and the United States.Such a GHS-F model is necessary from both scientific and operational perspectives,with the strength in providing spatially consistent flood definitions and spatially distributed flood risk classification considering the heterogeneity in vulnerability and resilience across the entire domain.Priorities in the development of such a GHS-F are suggested,emphasizing the user’s requirements and needs according to practical experiences with various flood response agencies.展开更多
There is limited understanding regarding the formation of multiple tropical cyclones(MTCs).This study explores the environmental conditions conducive to MTC formation by objectively determining the atmospheric circula...There is limited understanding regarding the formation of multiple tropical cyclones(MTCs).This study explores the environmental conditions conducive to MTC formation by objectively determining the atmospheric circulation patterns favorable for MTC formation over the western North Pacific.Based on 199 MTC events occurring from June to October 1980–2020,four distinct circulation patterns are identified:the monsoon trough(MT)pattern,accounting for 40.3%of occurrences,the confluence zone(CON)pattern at 26.2%,the easterly wave(EW)pattern at 17.8%,and the monsoon gyre(MG)pattern at 15.7%.The MT pattern mainly arises from the interaction between the subtropical high and the monsoon trough,with MTCs forming along the monsoon trough and its flanks.The CON pattern is affected by the subtropical high,the South Asian high,and the monsoon trough,with MTCs emerging at the confluence zone where the prevailing southwesterly and southeasterly flows converge.The EW pattern is dominated by easterly flows,with MTCs developing along the easterly wave train.MTCs in the MG pattern arise within a monsoon vortex characterized by strong southwesterly flows.A quantitative analysis further indicates that MTC formation in the MT pattern is primarily governed by mid-level vertical velocity and low-level vorticity,while mid-level humidity and vertical velocity are significantly important in the other patterns.The meridional shear and convergence of zonal winds are essential in converting barotropic energy from the basic flows to disturbance kinetic energy,acting as the primary source for eddy kinetic energy growth.展开更多
The development of tin-based devices with low toxicity is critical for the commercial viability of perovskite solar cells.However because tin halide is a stronger Lewis acid,its crystallization rate is extremely fast,...The development of tin-based devices with low toxicity is critical for the commercial viability of perovskite solar cells.However because tin halide is a stronger Lewis acid,its crystallization rate is extremely fast,resulting in the formation of numerous defects that affect the device performance of tin-based perovskite solar cells.Herein,propylamine hydrobromide(PABr)was added to the perovskite precursor solution as an additive to passivate defects and fabricate more uniform and dense perovskite films.Because propylamine cations are too large to enter the perovskite lattices,they only exist at the grain boundary to passivate surface defects and promote crystal growth in a preferred orientation.The PABr additive raises the average short-circuit current density from 19.45 to 25.47 mA·cm^(-2)by reducing carrier recombination induced by defects.Furthermore,the device’s long-term illumination stability is improved after optimization,and the hysteresis effect is negligible.The addition of PABr results in a power conversion efficiency of 9.35%.展开更多
Differentiation of human bone marrow-derived mesenchymal stem cells(hMSCs)is regulated by a variety of cues of their surrounding microenvironments.In particular,mechanical properties of cell culture matrices have been...Differentiation of human bone marrow-derived mesenchymal stem cells(hMSCs)is regulated by a variety of cues of their surrounding microenvironments.In particular,mechanical properties of cell culture matrices have been recently disclosed to play a pivotal role in stem cell differentiation.However,it remains elusive how viscosity affects the chondrogenic differentiation of hMSCs during three-dimensional(3 D)culture.In this study,a 3 D culture system that was established by embedding viscous gelatin solution in chemically cross-linked gelatin hydrogels was used for 3 D culture of hMSCs in gelatin solutions with different viscosities.The influence of solution viscosity on chondrogenic differentiation of hMSCs was investigated.Viscous gelatin solutions promoted cell proliferation in the order of low,middle and high viscosity while elastic hydrogels restricted cell proliferation.High viscosity gelatin solution led to increased production of the cartilaginous matrix.Under the synergistic stimulation of chondrogenic induction factors,high viscosity was beneficial for the chondrogenic differentiation of hMSCs.The results suggested the role of viscosity should be considered as one of the dominant mechanical cues affecting stem cell differentiation.展开更多
We report on a new type of amperometric glucose biosensor that was made by integration of glucose oxidase (GOD) with palladium nanoparticles/reduce graphene oxide (Pd/RGO) nanocomposite. The Pd/RGO was prepared by a o...We report on a new type of amperometric glucose biosensor that was made by integration of glucose oxidase (GOD) with palladium nanoparticles/reduce graphene oxide (Pd/RGO) nanocomposite. The Pd/RGO was prepared by a one-step reduction method in which the palladium nanoparticles and the reduced graphene oxide (RGO) were simultaneously accomplished from the reduction of dispersed solution of PdCl2 and graphite oxide (GO) with hydrazine. The asprepared nanocomposite exhibits favorable electrocatalytic activities towards the oxidation of H2O2, which makes it a good platform for the construction of the glucose biosensor. The analytical performance of the glucose biosensor is fully evaluated. It shows good analytical properties in terms of a short response time (3 s), high sensitivity (14.1 μA/mM), and low detection limit (0.034 mM). In addition, the effects of pH value, applied potential, electroactive interference and the stability of the biosensor were discussed as well.展开更多
Introduction:This study protocol specifies the primary research line and theoretical framework of the 2023 Survey of the Psychology and Behavior of the Chinese Population.It aims to establish a consistent database of ...Introduction:This study protocol specifies the primary research line and theoretical framework of the 2023 Survey of the Psychology and Behavior of the Chinese Population.It aims to establish a consistent database of Chinese residents'psychological and behavioral surveys through multi-center and large-sample cross-sectional surveys to provide robust data support for developing research in related fields.It will track the public's physical and psychological health more comprehensively and systematically.Methods:The study was conducted from June 20,2023 to August 31,2023,using stratified and quota sampling methods.A total of 150 cities across 800 communities/villages were surveyed,selected from China(Despite extensive coordination,we have been unable to contact our counterparts in the Taiwan region of China to obtain relevant statistical data).The questionnaires were distributed to the public one-on-one and face-to-face by trained surveyors.The questionnaires included basic information about the individual,personal health status,basic information about the family,the social environment in which the individual lives,psychological condition scales,behavioral level scales,other scales,and attitudes towards topical social issues.Supervisors conducted quality control during the distribution process and returned questionnaires,logically checked and cleaned for data analysis.Discussion:Data collection has been finished,and scientific outputs based on this data will support the development of health promotion strategies in China and globally.In the aftermath of the pandemic,it will guide policymakers and healthcare organizations to improve their existing policies and services to maximize the physical and mental health of the Chinese population.Trial Registration:This study was filed in the National Health Security Information Platform(Record No.:MR-37-23-017876)and officially registered in the China Clinical Trials Registry(Registration No.:ChiCTR2300072573).展开更多
Anas poecilorhyncha is one of improved variety of mallards, which was the protected bird species listed by International Union for Conservation of Nature （1UCN）. Little is known until now about behavioral characteri...Anas poecilorhyncha is one of improved variety of mallards, which was the protected bird species listed by International Union for Conservation of Nature （1UCN）. Little is known until now about behavioral characteristics of the mallard. The objective of this study was to compare the behavioral differentials between A. poecilorhyncha and domestic duck in order to make a strategy to manage A. poecilorhyncha under the condition of animal welfare. A total of 180 birds were distributed into six groups with 30 birds for each group. They were placed in a room of 3 m ~ 4 m and fed for one year old. Sansui ducks, a kind of native domestic duck （Sansui laying duck） were used for behavioral comparison. Two different rooms in the same building were applied, one room for A. poecilorhyncha and another one for Sansui ducks. All behaviors for A. poecilorhyncha and Sansui ducks were coded using the program The Observer XT 11.5 （Noldus Information Technology, Beijing）. The duration of observation was from 8：00 am to 18：00 pm daily and lasted 5 d. The results showed that there were similar behavioral percentages between A. poecilorhyncha and domestic duck. Percentages of standing activity spent for A. poecilorhyncha and Sansui duck were 34.59% and 30.25%, respectively. Accordingly, the activities, such as wing plugging, preening and head stretching, were more than 5.51%. The other activities, including walking, drinking and tail wagging, occupied less proportions （〈 3%）. While the specific behaviors, like aggression, alerting, wing dithering, clawing, nodding, pendulum clawing and crawling, took less than 1% of percentage. There were large differences between A. poecilorhyncha and domestic duck when comparing eight behavioral peaks. Lag sequential analysis was used to calculate frequency of transition between a pair of activities. Some parameters were very significant, like the frequency value from foraging converted to drinking in Sansui duck was 369-515, but 37-65 in A. poecilorhyncha. The best explaining could be given that Sansui duck was better domesticated than spot-billed duck. This study provides the basic data to study and develop spot-billed duck.展开更多
基金supported by the Jilin Province Health Science and Technology Ability Improvement Project(2023JL057).
文摘Objective:Triple-negative breast cancer(TNBC)is highly aggressive and lacks an effective targeted therapy.This study aimed to elucidate the functions and possible mechanisms of action of zinc finger miz-type containing 2(ZMIZ2)and minichromosome maintenance complex component 3(MCM3)in TNBC progression.Methods:The relationship between ZMIZ2 expression and clinical characteristics of TNBC was investigated.In vitro and in vivo experiments were performed to investigate the role of ZMIZ2 dysregulation in TNBC cell malignant behaviors.The regulatory relationship between ZMIZ2 and MCM3 was also explored.Transcriptome sequencing was performed to elucidate possible mechanisms underlying the ZMIZ2/MCM3 axis in TNBC.Results:High ZMIZ2 expression levels were associated with the malignant degree of TNBC.ZMIZ2 overexpression promoted TNBC cell proliferation,migration,and invasion;inhibited apoptosis;and induced G1 phase cell cycle arrest,whereas knockdown of ZMIZ2 had the opposite effect.ZMIZ2 directly targeted and positively regulated MCM3 expression.MCM3 knockdown reversed the effect of ZMIZ2 overexpression on TNBC tumor growth both in vitro and in vivo.High MCM3 expression levels were linked to the degree of malignancy and poor prognosis in TNBC.The differentially expressed genes associated with the ZMIZ2/MCM3 axis were significantly enriched in multiple pathways,such as the mitogen-activated protein kinase(MAPK),mechanistic target of rapamycin(mTOR),Wnt,and Ras signaling pathways,as verified by The Cancer Genome Atlas data.Conclusions:ZMIZ2 and MCM3 were highly expressed in TNBC.ZMIZ2 promoted the development by positively regulating MCM3 expression.Key pathways,such as the Ras/MAPK,phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mTOR,and Wnt signaling pathways,may be key downstreammechanisms.
基金supported by the National Natural Science Foundation of China under Grant 61825104, in part by the National Natural Science Foundation of China under Grants 61801518, 62201582in part by the National Key R&D Program of China under Grant 2022YFC3301300+3 种基金in part by the Key Research and Development Program of Shaanxi under Grant 2022KW-03in part by the Young Talent fund of University Association for Science and Technology in Shaanxi under Grant 20210111in part by the Natural Science Basic Research Program of Shaanxi under Grant 2022JQ-632in part by Innovative Cultivation Project of School of Information and Communication of National University of Defense Technology under Grant YJKT-ZD-2202
文摘Extensive research attentions have been devoted to studying cooperative cognitive radio networks(CCRNs),where secondary users(SU)providing cooperative transmissions can be permitted by primary users(PU)to use spectrum.In order to maximize SU’s utility,SU may transmit its own information during the period of cooperative transmission,which stimulates the use of covert transmission against PU’s monitoring.For this sake,this article reviews the motivations of studying covert communications in CCRN.In particular,three intelligent covert transmission approaches are developed for maximizing SU’s utility in CCRNs,namely,intelligent parasitic covert transmission(IPCT),intelligent jammer aided covert transmission(IJCT)and intelligent reflecting surface assisted covert transmission(IRSC).Further,some raw performance evaluations are discussed,and a range of potential research directions are also provided.
基金supported by National Natural Science Foundation of China (No. 51674032)
文摘The accuracy of laser-induced breakdown spectroscopy(LIBS) quantitative method is greatly dependent on the amount of certified standard samples used for training. However, in practical applications, only limited standard samples with labeled certified concentrations are available. A novel semi-supervised LIBS quantitative analysis method is proposed, based on co-training regression model with selection of effective unlabeled samples. The main idea of the proposed method is to obtain better regression performance by adding effective unlabeled samples in semisupervised learning. First, effective unlabeled samples are selected according to the testing samples by Euclidean metric. Two original regression models based on least squares support vector machine with different parameters are trained by the labeled samples separately, and then the effective unlabeled samples predicted by the two models are used to enlarge the training dataset based on labeling confidence estimation. The final predictions of the proposed method on the testing samples will be determined by weighted combinations of the predictions of two updated regression models. Chromium concentration analysis experiments of 23 certified standard high-alloy steel samples were carried out, in which 5 samples with labeled concentrations and 11 unlabeled samples were used to train the regression models and the remaining 7 samples were used for testing. With the numbers of effective unlabeled samples increasing, the root mean square error of the proposed method went down from 1.80% to 0.84% and the relative prediction error was reduced from 9.15% to 4.04%.
基金supported by grants from JSPS/MEXT KAKENHI(JP19H05302 and JP21H00295 to N.W.)the MOST-RIKEN Collaboration Project(2021YFE0108000 to J.L.and N.W.)Translation Research Programs from Fukushima Prefecture(to K.S.).
文摘Myc belongs to a family of proto-oncogenes that encode transcription factors.The overexpression of c-Myc causes many types of cancers.Recently,we established a system for screening c-Myc inhibitors and identified antimycin A by screening the RIKEN NPDepo chemical library.The specific mechanism of promoting tumor cell metastasis by high c-Myc expression remains to be explained.In this study,we screened approximately 5,600 microbial extracts using this system and identified a broth prepared from Streptomyces sp.RK19-A0402 strongly inhibits c-Myc transcriptional activity.After purification of the hit broth,we identified compounds closely related to the aglycone of cytovaricin and had a structure similar to that of oligomycin A.Similar to oligomycin A,the hit compounds inhibited mitochondrial complex V.The mitochondria dysfunction caused by the compounds induced the production of reactive oxygen species(ROS),and the ROS activated GSK3α/βthat phosphorylated c-Myc for ubiquitination.This study provides a successful screening strategy for identifying natural products as potential c-Myc inhibitors as potential anticancer agents.
基金This work was supported by the Beijing Natural Science Foundation(M23008)the National Key Research and Development Program of China(2018YFE0207300)+2 种基金Beijing Municipal Science&Technology Commission(Z211100002521021)the National High Level Hospital Clinical Research Funding(2022-PUMCH-B-124)Key Research and Development Plan of Hebei Province,Special Health Innovation Project(22377744D).
文摘Chronic liver disease(CLD)entails elevated risk of COVID-19 severity and mortality.The effectiveness of the booster dose of inactivated SARS-CoV-2 vaccine in stimulating antibody response in CLD patients is unclear.Therefore,we conducted a cross-sectional study involving 237 adult CLD patients and 170 healthy controls(HC)to analyze neutralizing antibodies(NAbs)against SARS-CoV-2 prototype and BA.4/5 variant,anti-receptor binding domain(RBD)IgG,and total anti-SARS-CoV-2 antibodies.Serum levels of the total anti-SARS-CoV-2 antibodies,anti-RBD IgG and inhibition efficacy of NAbs were significantly elevated in CLD patients after the booster dose compared with the pre-booster dose,but were relatively lower than those of HCs.Induced humoral responses decreased over time after booster vaccination.The neutralization efficiency of the serum against BA.4/5 increased but remained below the inhibition threshold.All four SARS-CoV-2 antibodies,including total anti-SARS-CoV-2 antibodies,anti-RBD IgG and NAbs against prototype and BA.4/5,were lower in patients with severe CLD than those with non-severe CLD.After booster shot,age and time after the last vaccine were the risk factors for seropositivity of NAb against BA.4/5 in CLD patients.Additionally,white blood cell counts and hepatitis B core antibodies were the protective factors,and severe liver disease was the risk factor associated with seropositivity of total anti-SARS-CoV-2 antibodies.Overall,our data uncovered that antibody responses were improved in CLD patients and peaked at 120 days after the booster vaccines.All antibodies excepting total anti-SARS-CoV-2 antibodies declined after peak.CLD patients exhibited impaired immunologic responses to vaccination and weakened NAbs against BA.4/5,which hindered the protective effect of the booster shot against Omicron prevalence.Cellular immune responses should be further evaluated to determine the optimal vaccine regimen for CLD patients.
基金the National Natural Science Foundation of China(Nos.52070036,U20A20322)the Fundamental Research Funds for the Central Universities(No.2412018ZD042)for their financial support。
文摘The biosecurity hazards caused by pathogenic fungus have been widely concerned.Given the long-term coexistence of eukaryotic pathogens and quorum sensing bacteria in different habitats in environments,we hypothesized that they have social interactions via signal molecules.In this work,we firstly discovered the well-known bacterial signal molecules play an adverse role in the cell morphology and metabolism in a model pathogen Trichosporon asahii.N-Tetradecanoyl-L-homoserine lactone(C14-HSL)was discovered to increase pathogen hazards of T.asahii,which limited mycelium by 52%,but enhanced cell aggregation by 93%.Higher fluorescence intensity of tryptophan(59%)and aromatic protein(2-fold)contents after the treatment of C14-HSL,indicating that aromatic proteins helped aggregate Trichosporon and showed hydrophobicity.Transcriptome analysis revealed that C14-HSL upregulated the shikimate pathway(above1-fold)located in downstream of tricarboxylic acid cycle,which contributed to the synthesis of more aromatic proteins and the formation of larger flocs.The limited mycelial growth of T.asahii attributed to the up-regulated expressions of cell cycle process.The fungal transboundary response to bacterial C14-HSL was controlled by signal transduction pathways.This study provides new insights into the co-evolution of bacterial and pathogenic fungi in microecosystems.
基金supported by research grants from the JSPS/MEXT KAKENHI(JP19H05302 and JP21H00295 to N.W.)the MOSTRIKEN Collaboration Project(2021YFE0108000 to J.L.and N.W.).
文摘β-transducin repeat-containing protein(β-TrCP)is an F-box protein subunit of the E3 Skp1-Cullin-F box(SCF)type ubiquitin-ligase complex,and provides the substrate specificity for the ligase.To find potent ligands ofβ-TrCP useful for the proteolysis targeting chimera(PROTAC)system usingβ-TrCP in the future,we developed a high-throughput screening system for small moleculeβ-TrCP ligands.We screened the chemical library utilizing the system and obtained several hit compounds.The effects of the hit compounds on in vitro ubiquitination activity of SCFβ-TrCP1 and on downstream signaling pathways were examined.Hit compounds NPD5943,NPL62020-01,and NPL42040-01 inhibited the TNFα-induced degradation of IκBαand its phosphorylated form.Hence,they inhibited the activation of the transcription activity of NF-κB,indicating the effective inhibition ofβ-TrCP by the hit compounds in cells.Next,we performed an in silico analysis of the hit compounds to determine the important moieties of the hit compounds.Carboxyl groups of NPL62020-01 and NPL42040-01 and hydroxyl groups of NPD5943 created hydrogen bonds withβ-TrCP similar to those created by intrinsic target phosphopeptides ofβ-TrCP.Our findings enhance our knowledge of useful small molecule ligands ofβ-TrCP and the importance of residues that can be ligands ofβ-TrCP.
基金CAMS Innovation Fund for Medical Science,Grant/Award Number:2021-I2M-1-034The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01。
文摘Background:Alzheimer's disease(AD)and lung cancer are leading causes of mortality among the older population.Epidemiological evidence suggests an antagonistic relationship between them,whereby patients with AD exhibit a reduced risk of developing cancer and vice versa.However,the precise mechanism by which AD antagonizes lung cancer progression warrants further elucidation.Methods:To this end,we established a co-morbidity model using 5xFAD transgenic mice induced with the carcinogen urethane.We visualized and quantified surface lung tumor colonies,assessed pathological parameters associated with lung cancer and AD using histopathological analysis,and employed single-cell sequencing and molecular pathological analyses to explore the mechanisms by which AD confers resistance to lung cancer.Results:Our findings revealed a significant reduction in lung tumor incidence in the AD group compared with that in the wild-type(WT)group.The results indicated a close association between AD-induced inhibition of lung tumor progression and iron homeostasis imbalance and increased oxidative stress.Moreover,greater CD8^(+)T cytotoxic lymphocyte and effector natural killer cell infiltration in the lung tumor tissues of AD mice and enhanced CD8^(+)T cytotoxic lymphocyte-mediated killing of target cells may be the primary factors contributing to the inhibition of lung tumor growth in the presence of AD.Conclusion:This study identified essential mechanisms through which AD suppresses lung tumorigenesis,thereby providing targets for potential therapeutic interventions in these diseases.
文摘开花时间对植物的繁殖成功至关重要。广泛分布的物种经常发生开花时间的分化,从而能够更好地适应不同的环境条件。为了探索植物开花行为发生适应性分化的分子机制,首先要明确调控开花行为的遗传通路。本文梳理了植物各类群调控开花时间的遗传通路,以期为开花时间适应性分化的分子机制研究提供依据。植物从营养生长向繁殖转变时,其开花行为主要受到光照、温度、水分等外界环境因子和赤霉素等内在因素的影响。通过对模式植物拟南芥(Arabidopsis thaliana)和其他类群的研究,总结出了调控植物开花时间的6条通路,包括日照长度和光质影响开花的光依赖通路,长时间冷暴露后促进植物开花的春化通路,高温或低温环境影响开花的温度通路,以及赤霉素通路、年龄通路和自主通路3条内部调节过程。植物开花时间调控的6条上游通路信号传递到下游的开花整合基因FT(FLOWERING LOCUS T)和SOC1(SUPPRESSOR OF OVER-EXPRESSION OF CONSTANS 1),整合基因将这些复杂的调节因子整合后进一步传递到下游花分生组织,从而启动开花。此外,非编码RNA、转座子对开花时间的调控也具有重要作用。部分遗传通路被证实在植物适应环境的过程中起到了重要作用。目前对植物开花调控的研究已经有一百多年历史,理论相对成熟。然而,仍然存在许多具有争议和未解决的问题,如开花基因的表达方式、开花行为的特殊调控机制、开花时间变异的适应性意义等等,需要更进一步的研究。
基金the National Natural Science Foundation of China(Grants 11772055,11532009,11521062,11372042).
文摘Collective cells are organized to form specific patterns which play important roles in various physiological and pathological processes,such as tissue morphogenesis,wound healing,and cancer invasion.Compared to single cell behaviors,which has been intensively studied from many aspects(cell migration,adhesion,polarization,proliferation,etc.)and at various scales(molecular,subcellular,and cellular),the multiple cell behaviors are relatively less understood,particularly in a quantitative manner.In this paper,we will present our recent studies of collective polarization and orientation of multiple cells through both experimental measurement and theoretical modeling,including those cell behaviors on/in 2D and 3D substrate/tissue.We find that the collective cell behaviors,including polarization,alignment and migration are closely related to local stress states in cell layer or tissue,which demonstrate the crucial roles of mechanical forces in the living organisms.Specifically,the cells prefer to polarize and align along the maximum principal stress in the cell layer,and the aspect ratio of cell increases with the in-plane maximum shear stress,suggesting that the maximum shear stress is the underlying driving force of cell polarization and orientation.This theory of stress-driven cell behaviors of polarization and orientation provides a new perspective for understanding cell behaviors in living organisms and the guideline for tissue engineering in biomedical applications.
基金This study was supported by the National Key R&D Program of China(Grant No.2017YFA0604300)the National Natural Science Foundation of China(Grant Nos.41861144014,41775106 and U1811464)+1 种基金the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(Grant No.2017ZT07X355)the project of the Chinese Ministry of Emergency Management on“Catastrophe Evaluation Modeling Study”.
文摘The prolonged mei-yu/baiu system with anomalous precipitation in the year 2020 has swollen many rivers and lakes,caused flash flooding,urban flooding and landslides,and consistently wreaked havoc across large swathes of China,particularly in the Yangtze River basin.Significant precipitation and flooding anomalies have already been seen in magnitude and extension so far this year,which have been exerting much higher pressure on emergency responses in flood control and mitigation than in other years,even though a rainy season with multiple ongoing serious flood events in different provinces is not that uncommon in China.Instead of delving into the causes of the uniqueness of this year’s extreme precipitation-flooding situation,which certainly warrants in-depth exploration,in this article we provide a short view toward a more general hydrometeorological solution to this annual nationwide problem.A“glocal”(global to local)hydrometeorological solution for floods(GHS-F)is considered to be critical for better preparedness,mitigation,and management of different types of significant precipitation-caused flooding,which happen extensively almost every year in many countries such as China,India and the United States.Such a GHS-F model is necessary from both scientific and operational perspectives,with the strength in providing spatially consistent flood definitions and spatially distributed flood risk classification considering the heterogeneity in vulnerability and resilience across the entire domain.Priorities in the development of such a GHS-F are suggested,emphasizing the user’s requirements and needs according to practical experiences with various flood response agencies.
基金supported by the National Natural Science Foundation of China(Grant No.42075015)the Science and Technology Commission of Shanghai Municipality,China(23DZ1204703).
文摘There is limited understanding regarding the formation of multiple tropical cyclones(MTCs).This study explores the environmental conditions conducive to MTC formation by objectively determining the atmospheric circulation patterns favorable for MTC formation over the western North Pacific.Based on 199 MTC events occurring from June to October 1980–2020,four distinct circulation patterns are identified:the monsoon trough(MT)pattern,accounting for 40.3%of occurrences,the confluence zone(CON)pattern at 26.2%,the easterly wave(EW)pattern at 17.8%,and the monsoon gyre(MG)pattern at 15.7%.The MT pattern mainly arises from the interaction between the subtropical high and the monsoon trough,with MTCs forming along the monsoon trough and its flanks.The CON pattern is affected by the subtropical high,the South Asian high,and the monsoon trough,with MTCs emerging at the confluence zone where the prevailing southwesterly and southeasterly flows converge.The EW pattern is dominated by easterly flows,with MTCs developing along the easterly wave train.MTCs in the MG pattern arise within a monsoon vortex characterized by strong southwesterly flows.A quantitative analysis further indicates that MTC formation in the MT pattern is primarily governed by mid-level vertical velocity and low-level vorticity,while mid-level humidity and vertical velocity are significantly important in the other patterns.The meridional shear and convergence of zonal winds are essential in converting barotropic energy from the basic flows to disturbance kinetic energy,acting as the primary source for eddy kinetic energy growth.
基金supported by the Talent Fund of Beijing Jiaotong University (No.2019RC058)the National Natural Science Foundation of China (Nos.62205013,62075009,62275013,and 12274020)。
文摘The development of tin-based devices with low toxicity is critical for the commercial viability of perovskite solar cells.However because tin halide is a stronger Lewis acid,its crystallization rate is extremely fast,resulting in the formation of numerous defects that affect the device performance of tin-based perovskite solar cells.Herein,propylamine hydrobromide(PABr)was added to the perovskite precursor solution as an additive to passivate defects and fabricate more uniform and dense perovskite films.Because propylamine cations are too large to enter the perovskite lattices,they only exist at the grain boundary to passivate surface defects and promote crystal growth in a preferred orientation.The PABr additive raises the average short-circuit current density from 19.45 to 25.47 mA·cm^(-2)by reducing carrier recombination induced by defects.Furthermore,the device’s long-term illumination stability is improved after optimization,and the hysteresis effect is negligible.The addition of PABr results in a power conversion efficiency of 9.35%.
基金financially supported by JSPS KAKENHI(Nos.18K19947,18K19945 and 19H04475)。
文摘Differentiation of human bone marrow-derived mesenchymal stem cells(hMSCs)is regulated by a variety of cues of their surrounding microenvironments.In particular,mechanical properties of cell culture matrices have been recently disclosed to play a pivotal role in stem cell differentiation.However,it remains elusive how viscosity affects the chondrogenic differentiation of hMSCs during three-dimensional(3 D)culture.In this study,a 3 D culture system that was established by embedding viscous gelatin solution in chemically cross-linked gelatin hydrogels was used for 3 D culture of hMSCs in gelatin solutions with different viscosities.The influence of solution viscosity on chondrogenic differentiation of hMSCs was investigated.Viscous gelatin solutions promoted cell proliferation in the order of low,middle and high viscosity while elastic hydrogels restricted cell proliferation.High viscosity gelatin solution led to increased production of the cartilaginous matrix.Under the synergistic stimulation of chondrogenic induction factors,high viscosity was beneficial for the chondrogenic differentiation of hMSCs.The results suggested the role of viscosity should be considered as one of the dominant mechanical cues affecting stem cell differentiation.
文摘We report on a new type of amperometric glucose biosensor that was made by integration of glucose oxidase (GOD) with palladium nanoparticles/reduce graphene oxide (Pd/RGO) nanocomposite. The Pd/RGO was prepared by a one-step reduction method in which the palladium nanoparticles and the reduced graphene oxide (RGO) were simultaneously accomplished from the reduction of dispersed solution of PdCl2 and graphite oxide (GO) with hydrazine. The asprepared nanocomposite exhibits favorable electrocatalytic activities towards the oxidation of H2O2, which makes it a good platform for the construction of the glucose biosensor. The analytical performance of the glucose biosensor is fully evaluated. It shows good analytical properties in terms of a short response time (3 s), high sensitivity (14.1 μA/mM), and low detection limit (0.034 mM). In addition, the effects of pH value, applied potential, electroactive interference and the stability of the biosensor were discussed as well.
基金Research project of China Medical Education Association,Grant/Award Number:CMEA[2023]:No.0003。
文摘Introduction:This study protocol specifies the primary research line and theoretical framework of the 2023 Survey of the Psychology and Behavior of the Chinese Population.It aims to establish a consistent database of Chinese residents'psychological and behavioral surveys through multi-center and large-sample cross-sectional surveys to provide robust data support for developing research in related fields.It will track the public's physical and psychological health more comprehensively and systematically.Methods:The study was conducted from June 20,2023 to August 31,2023,using stratified and quota sampling methods.A total of 150 cities across 800 communities/villages were surveyed,selected from China(Despite extensive coordination,we have been unable to contact our counterparts in the Taiwan region of China to obtain relevant statistical data).The questionnaires were distributed to the public one-on-one and face-to-face by trained surveyors.The questionnaires included basic information about the individual,personal health status,basic information about the family,the social environment in which the individual lives,psychological condition scales,behavioral level scales,other scales,and attitudes towards topical social issues.Supervisors conducted quality control during the distribution process and returned questionnaires,logically checked and cleaned for data analysis.Discussion:Data collection has been finished,and scientific outputs based on this data will support the development of health promotion strategies in China and globally.In the aftermath of the pandemic,it will guide policymakers and healthcare organizations to improve their existing policies and services to maximize the physical and mental health of the Chinese population.Trial Registration:This study was filed in the National Health Security Information Platform(Record No.:MR-37-23-017876)and officially registered in the China Clinical Trials Registry(Registration No.:ChiCTR2300072573).
文摘Anas poecilorhyncha is one of improved variety of mallards, which was the protected bird species listed by International Union for Conservation of Nature （1UCN）. Little is known until now about behavioral characteristics of the mallard. The objective of this study was to compare the behavioral differentials between A. poecilorhyncha and domestic duck in order to make a strategy to manage A. poecilorhyncha under the condition of animal welfare. A total of 180 birds were distributed into six groups with 30 birds for each group. They were placed in a room of 3 m ~ 4 m and fed for one year old. Sansui ducks, a kind of native domestic duck （Sansui laying duck） were used for behavioral comparison. Two different rooms in the same building were applied, one room for A. poecilorhyncha and another one for Sansui ducks. All behaviors for A. poecilorhyncha and Sansui ducks were coded using the program The Observer XT 11.5 （Noldus Information Technology, Beijing）. The duration of observation was from 8：00 am to 18：00 pm daily and lasted 5 d. The results showed that there were similar behavioral percentages between A. poecilorhyncha and domestic duck. Percentages of standing activity spent for A. poecilorhyncha and Sansui duck were 34.59% and 30.25%, respectively. Accordingly, the activities, such as wing plugging, preening and head stretching, were more than 5.51%. The other activities, including walking, drinking and tail wagging, occupied less proportions （〈 3%）. While the specific behaviors, like aggression, alerting, wing dithering, clawing, nodding, pendulum clawing and crawling, took less than 1% of percentage. There were large differences between A. poecilorhyncha and domestic duck when comparing eight behavioral peaks. Lag sequential analysis was used to calculate frequency of transition between a pair of activities. Some parameters were very significant, like the frequency value from foraging converted to drinking in Sansui duck was 369-515, but 37-65 in A. poecilorhyncha. The best explaining could be given that Sansui duck was better domesticated than spot-billed duck. This study provides the basic data to study and develop spot-billed duck.
