In many applications,flow measurements are usually sparse and possibly noisy.The reconstruction of a high-resolution flow field from limited and imperfect flow information is significant yet challenging.In this work,w...In many applications,flow measurements are usually sparse and possibly noisy.The reconstruction of a high-resolution flow field from limited and imperfect flow information is significant yet challenging.In this work,we propose an innovative physics-constrained Bayesian deep learning approach to reconstruct flow fields from sparse,noisy velocity data,where equationbased constraints are imposed through the likelihood function and uncertainty of the reconstructed flow can be estimated.Specifically,a Bayesian deep neural network is trained on sparse measurement data to capture the flow field.In the meantime,the violation of physical laws will be penalized on a large number of spatiotemporal points where measurements are not available.A non-parametric variational inference approach is applied to enable efficient physicsconstrained Bayesian learning.Several test cases on idealized vascular flows with synthetic measurement data are studied to demonstrate the merit of the proposed method.展开更多
Considering the complexity of the networks and the need for telecommunication operators （Telco） to present innovations to their clients, the quickest possible, one of the solutions for this complexity could be to ce...Considering the complexity of the networks and the need for telecommunication operators （Telco） to present innovations to their clients, the quickest possible, one of the solutions for this complexity could be to centralize its configuration. Thus the SDN （software-defmed networking） concept may be an important solution. This paper suggests the implementation of a tool to support the development and testing of networks and services before they are put into production. The use of a tool that simplifies the configuration of a network service makes the networks and services to be less susceptible to errors and failures by those who set them up, thus allowing telecom operators, among others, to be able to create new services, improve the monitorization of their human resources and, above all, improve their fmancial results. In the end, success will be achieved because with a simple interaction and basic knowledge we are able to manage network services.展开更多
Tooth decay affects most of the population in developed countries. The multifactorial etiology of the disease includes multiple bacterial species, S. mutans is the main pathogen associated with the disease. This bacte...Tooth decay affects most of the population in developed countries. The multifactorial etiology of the disease includes multiple bacterial species, S. mutans is the main pathogen associated with the disease. This bacterium adheres to the tooth surface and allows the colonization of other microorganisms resulting in dental biofilm. Several therapeutic agents are available to treat or prevent tooth decay, but none, with the exception of fluoride, has significantly influenced the disease’s global burden. Moreover, the probable development of resistance of microorganisms to existing antibacterial agents and the scarcity of good antimicrobial agents motivates this effort for innovation. The detailed knowledge obtained in recent years on the S. mutans allowed the identification of potential targets in this microorganism, enabling the development of specific drugs to combat tooth decay. Thus, the identification of potential targets in these pathogens is the first step in the discovery process of new therapeutic agents. Currently, the experimental assays used for this purpose are expensive and time consuming. In contrast, bioinformatics methods to predict drug targets are cheap, quick and workaday in the biotechnology. This article will review the potential drug targets in S. mutans, as well as the bioinformatics methods used to identify these targets and effective drugs for specific pharmacological treatment of dental caries.展开更多
Background:Studies have shown that heart rate variability(HRV)is a predictor of the prognosis of cardiovascular diseases.Contact heartbeat monitoring equipment is widely used,especially in hospitals,and benefits from ...Background:Studies have shown that heart rate variability(HRV)is a predictor of the prognosis of cardiovascular diseases.Contact heartbeat monitoring equipment is widely used,especially in hospitals,and benefits from the rapidity and accuracy of the detection of physiological health indicators.However,long-term contact with equipment has many adverse effects.The purpose of this study was to improve the accuracy of HRV detection via noncontact equipment,thus enabling HRV to be assessed in various scenarios.Methods:A novel deep learning approach was proposed for measuring heartbeats through camera videos.First,we performed facial segmentation and divided the face into 16 grid cells with different light balance scores.After the trend is filtered by the Hamming window,a transformer-based neural network is used to further filter the signal.Finally,heart rate(HR)and HRV are estimated.Results:We used 1 million synthetic data points for pretraining and a public dataset in combination with a dataset that we constructed for task training.The final results were obtained on a test dataset that we constructed.The accuracy for HR with a low light balance score(0.867-0.983)was greater than that with a high score(0.667-0.750).Our method had higher accuracy in estimating HR than traditional filtering methods(0.167-0.417)and state-of-the-art neural network filtering methods(0.783-0.917)did.The root mean square error of the HRV from the time domain was the lowest,and the correlation index score was the highest for the HRV from the frequency domain estimated by our method compared with those estimated by two neural networks.Conclusions:Light balance,large sample training,and two-stage training can improve the accuracy of HRV estimation.展开更多
AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP).METHODS: Serum levels of interleukin (I...AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP).METHODS: Serum levels of interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM-1), soluble tumor necrosis factor receptor II (sTNF-RII), proteasome, and β-catenin were measured in 479 subjects categorized into four groups: (1) HCC concurrent with hepatitis C virus (HCV) infection (n = 192); (2) HCV related liver cirrhosis (LC) (n = 96); (3) Chronic hepatitis C (CHC) (n = 96); and (4) Healthy controls (n = 95). The R package and different modules for binary and multi-class classifiers based on generalized linear models were used to model the data. Predictive power was used to evaluate the performance of the model. Receiver operating characteristic curve analysis over pairs of groups was used to identify the best cutoffs differentiating the different groups.RESULTS: We revealed mathematical models, based on a binary classifier, made up of a unique panel of serum proteins that improved the individual performance of AFP in discriminating HCC patients from patients with chronic liver disease either with or without cirrhosis. We discriminated the HCC group from the cirrhotic liver group using a mathematical model (-11.3 + 7.38 × Prot + 0.00108 × sICAM + 0.2574 × β-catenin + 0.01597 × AFP) with a cutoff of 0.6552, which achieved 98.8% specificity and 89.1% sensitivity. For the discrimination of the HCC group from the CHC group, we used a mathematical model [-10.40 + 1.416 × proteasome + 0.002024 × IL + 0.004096 × sICAM-1 + (4.251 × 10<sup>-4</sup>) × sTNF + 0.02567 × β-catenin + 0.02442 × AFP] with a cutoff 0.744 and achieved 96.8% specificity and 89.7% sensitivity. Additionally, we derived an algorithm, based on a binary classifier, for resolving the multi-class classification problem by using three successive mathematical model predictions of liver disease status.CONCLUSION: Our proposed mathematical model may be a useful method for the early detection of different statuses of liver disease co-occurring with HCV infection.展开更多
Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are c...Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are closely associated with a range of diseases,including neurodegenerative disorders,cancer and infectious diseases,highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis,and exploring potential therapeutic interventions.In this review,we delineate recent advancements in LLPS research,emphasizing its pathological relevance,therapeutic considerations,and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations.Additionally,we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability.By providing comprehensive insights into current LLPS-related bioinformatics resources,this review highlights its implications for human health and disease.展开更多
Background:Anthrax is a zoonotic infectious disease caused by Bacillus anthracis.Investigating the spatiotemporal characteristics of anthrax and the impact of meteorological factors on the incidence of anthrax is help...Background:Anthrax is a zoonotic infectious disease caused by Bacillus anthracis.Investigating the spatiotemporal characteristics of anthrax and the impact of meteorological factors on the incidence of anthrax is helpful for the prevention and control of anthrax.Methods:At first,we applied the Granger causality test to explore the spatiotemporal characteristics of anthrax transmission between the counties and cities of Gannan Tibetan Autonomous Prefecture,Gansu Province of China.Then,we constructed three generalized linear models to analyze the impact of meteorological factors on the monthly number of anthrax cases in Gannan Tibetan Autonomous Prefecture.Finally,we developed an easy-to-use online web server that integrates the above functions.Results:This study developed an online service website(ASTM,http://www.combio-lezhang.online/anthrax/index.html)for the analysis and visualization of anthrax,which not only can investigate the correlation of anthrax among different regions in Gannan Tibetan Autonomous Prefecture,but also can analyze the correlation between meteorological factors and!the number of anthrax cases.Conclusions:Our study not only explored spatiotemporal characteristics of anthrax transmission,but also analyzed the impact of seven meteorological factors on the monthly number of anthrax cases.Meanwhile,the online service website which integrates the above functions is useful for the prevention and control of anthrax.展开更多
Making time-series forecasting in a robust way is a difficult task only based on the observed data of a non-linear system.In this work,a neural network computing framework,the spatiotemporal information conver-sion ma...Making time-series forecasting in a robust way is a difficult task only based on the observed data of a non-linear system.In this work,a neural network computing framework,the spatiotemporal information conver-sion machine(STICM),was developed to efficiently and accurately render a forecasting of a time series by employing a spatial-temporal information(STI)transformation.STICM combines the advantages of both the STI equation and the temporal convolutional network,which maps the high-dimensional/spatial data to the future temporal values of a target variable,thus naturally providing the forecasting of the target variable.From the observed variables,the STICM also infers the causal factors of the target variable in the sense of Granger causality,which are in turn selected as effective spatial information to improve the robustness of time-series forecasting.The STICM was successfully applied to both benchmark systems and real-world datasets,all of which show superior and robust performance in timeseries forecasting,even when the data were perturbed by noise.From both theoretical and computational viewpoints,the STICM has great potential in practical applications in artificial intelligence or as a model-free method based only on the observed data,and also opens a new way to explore the observed high-dimensional data in a dynamical manner for machine learning.展开更多
Background:Chronic kidney disease(CKD)is a global health issue,with renal fibrosis being a common pathway in CKD development.Histone modification plays crucial roles in transcriptional regulation,but their pathologica...Background:Chronic kidney disease(CKD)is a global health issue,with renal fibrosis being a common pathway in CKD development.Histone modification plays crucial roles in transcriptional regulation,but their pathological functions and mechanisms in CKD are not well understood.Methods:We utilized chromatin immunoprecipitation with next-generation DNA sequencing(ChIP-seq)and RNA-seq to evaluate the states and functions of H3 lysine 27 acetylation(H3K27ac)and H3 lysine 4 trimethylation(H3K4me3)in kidney of CKD mice.We identified epigenetic factors regulating H3K27ac through motif analysis.Expression of activating transcription factor 3(ATF3)in CKD mouse models and patients’kidneys was validated via immunofluorescence staining or Western blot.We further generated the Atf3 deficient(Atf3^(-/-)) mice to explore its effect in kidney function and fibrosis.ChIP-seq of H3K27ac from Atf3-/-CKD mice was employed to validate ATF3’s regulatory effects.We explored how ATF3 maintains the state of H3K27ac by integrating the data sources from multiple databases.Results:The states of H3K27ac and H3K4me3 were changed during CKD,and positively correlated with differential gene expression.ATF3 was highly expressed in kidney of both patients and mice with CKD,and co-localized with H3K27ac in genome,epigenetically regulating H3K27ac state.Atf3 deficient in CKD mice significantly ameliorated kidney dysfunction and fibrotic phenotype,and reduced H3K27ac levels at the ATF3 binding sites.Mechanically,ATF3 may facilitate H3K27ac maintenance by corrodinating histone acetyltransferase(HATs)-associated regulatory machinery during CKD.Conclusion:ATF3 promotes kidney injury and fibrosis in CKD by maintaining the state of H3k27ac via coordinating HATs regulatory machinery.展开更多
To the Editor:Sarcopenia,defined by the European Working Group on Sarcopenia in Older People(EWGSOP)as the presence of both low muscle mass and low muscle strength or performance,has emerged as a critical public healt...To the Editor:Sarcopenia,defined by the European Working Group on Sarcopenia in Older People(EWGSOP)as the presence of both low muscle mass and low muscle strength or performance,has emerged as a critical public health concern in aging populations.[1]Moreover,sarcopenic obesity(SO),first characterized by Baumgartner as the coexistence of sarcopenia and obesity,was another high-risk geriatric syndrome.[2]Obesity and sarcopenia often coexist in the aging population and exhibit strong bidirectional associations.A recent meta-analysis encompassing 106 clinical studies(N=167,151 older individuals)reported a pooled SO prevalence of 9%in both sexes.[3]Importantly,it revealed a 51%increased risk of all-cause mortality(pooled hazard ratio[HR]=1.51,95%confidence intetal[CI]1.14–2.02,P<0.001)among individuals with SO compared to their healthy counterparts.[3]Given its adverse health implications,emerging research underscores the need to approach SO as a distinct,multifactorial phenotype.Consequently,identifying robust predictors of SO is imperative for targeted interventions.展开更多
Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic disorder characterized by gastrointestinal inflammation.Cigarette smoke is a well-established risk factor for ...Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic disorder characterized by gastrointestinal inflammation.Cigarette smoke is a well-established risk factor for the development and exacerbation of CD while exerting a paradoxical protective effect against the onset of UC.The exact mechanisms by which cigarette smoke influences IBD,as well as the opposite effects in UC and CD,have long remained unexplained.Here,we demonstrated the detrimental impact of cigarette smoke on CD progression while highlighting its beneficial effects on UC,as evidenced by analyses of human sample data.Mouse models of CD and UC exposed to cigarette smoke presented phenotypes consistent with those observed in human disease.GPR15,previously reported to direct regulatory T(Treg)cell colon homing,was upregulated in the colon tissues of both chemically induced colitis models after smoke exposure.Importantly,Gpr15 deletion ameliorated smoke-induced CD while increasing UC severity in mice.Furthermore,our study revealed that cigarette smoke mediated GPR15 to amplify colonic T helper type 17(Th17)cell populations,thereby worsening the adverse effects of smoking on CD in mouse models.Moreover,cigarette smoke induced an increase in Treg cells through GPR15,which contributed to mitigating its impact on UC in mouse models.Moreover,in cigarette smoke-exposed CD and UC model mice,C57BL/6JGpt-Tg(human GPR15)transgenic mice presented phenotypes opposite those of Gpr15-deficient mice.Overall,our study offers mechanistic insights into the role of cigarette smokeinduced GPR15+T cells in mediating the divergent effects of smoking on UC and CD.展开更多
Background Birth defects constitute a significant public health issue worldwide,yet there is a lack of comprehensive population-based data for the Chinese population.Methods We analyzed data from the China National Po...Background Birth defects constitute a significant public health issue worldwide,yet there is a lack of comprehensive population-based data for the Chinese population.Methods We analyzed data from the China National Population-based Birth Defects Surveillance System from 2007 to 2021,we calculated the prevalence rates of selected birth defects,stratified by maternal residence,geographic region,maternal age,and infant sex.The Joinpoint regression model was utilized to assess trends and annual percent changes in prevalence.Results From 2007 to 2021,significant downward trends in prevalence were observed for neural tube defects(NTDs),hydrocephalus,cleft lip with or without palate(CL/P),limb reduction defects(LRD),omphalocele,Down syndrome,and tetralogy of Fallot(TOF).Conversely,upward trends were identified for hypospadias,cleft palate(CP),microtia/anotia,polydactyly,syndactyly,ventricular septal defect(VSD),atrial septal defect/patent foramen ovale(ASD/PFO),and patent ductus arteriosus(PDA).Younger mothers exhibited a higher prevalence of hydrocephalus,gastroschisis,CL/P,and polydactyly,while anotia/microtia,Down syndrome,and congenital heart diseases(CHDs)were more common in mothers aged 35 years or older.Significant variations in the prevalence of anencephalus,spina bifida,CL/P,anorectal atresia/stenosis,hypospadias,polydactyly,syndactyly,VSD,ASD/PFO,and PDA were found across different maternal residences and geographic regions.Conclusion This study highlights the diverse trends and prevalence patterns of major birth defects,underscoring the necessity for defect-specific public health interventions.展开更多
Background:The risk for chronic kidney disease(CKD)is influenced by genetic predisposition,sex,and lifestyle.Previous research indicates that coffee is a potentially protective factor in CKD.The current study aims to ...Background:The risk for chronic kidney disease(CKD)is influenced by genetic predisposition,sex,and lifestyle.Previous research indicates that coffee is a potentially protective factor in CKD.The current study aims to investigate whether sex disparity exists in the coffee–CKD association,and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.Methods:A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study,which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model.Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data(n=255,343).Analyses stratified by genetic predisposition,comorbidities,and sex hormones were performed.Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results.Results:Coffee was inversely associated with CKD in a dose-dependent manner.The effects of coffee did not differ across different strata of genetic risk for CKD,but were more evident among slower genetically predicted caffeine metabolizers.Significant sex disparity was observed(P value for interaction=0.013),in that coffee drinking was only associated with the risk reduction of CKD in females.Subgroup analysis revealed that testosterone and sex hormone-binding globulin(SHBG),but not estradiol,modified the coffee–CKD association.Conclusions:In addition to the overall inverse coffee–CKD association that was observed in the general population,we could also establish that a sex disparity existed,in that females were more likely to experience the benefit of the association.Testosterone and SHBG may partly account for the sex disparity.展开更多
Kawasaki Disease(KD)patients with co-occurrent coronary artery aneurysms(CAAs)are prone to thrombosis.This study explores the thrombotic influence of morphology and hemodynamics in KD patients with CAAs.Patient-specif...Kawasaki Disease(KD)patients with co-occurrent coronary artery aneurysms(CAAs)are prone to thrombosis.This study explores the thrombotic influence of morphology and hemodynamics in KD patients with CAAs.Patient-specific computed tomography angiogram images of 9 patients were used to rebuild coronary models(including 23 aneurysms;10 in thrombosed group,and 13 in non-thrombosed group)and perform computational simulations to obtain the hemodynamic parameters.The thrombosed and non-thrombosed groups were compared in terms of six parameters,namely,the maximum diameter(D_(max)),aspect ratio(R_(l/d)),shape,time-averaged wall shear stress(TAWSS),oscillatory shear index(OSI),and relative residence time(RRT).The results showed that:(1)In thrombosed aneurysms,there were several vortex structures(eddy zone),of which the position changed continuously in a cardiac cycle.In non-thrombosed aneurysms,the streamlines showed a large streaming zone.(2)Abnormal hemodynamic areas of aneurysms with thrombosis tended to appear in the same region(especially the proximal and near myocardial side of aneurysms).(3)In the non-thrombosed group,there was a correlation between the morphological and hemodynamic parameters.In thrombosed aneurysms,the flow pulsatility has a significant impact on the flow pattern.The thrombosed coronary aneurysms exhibited more risk factors and the co-location of hemodynamic abnormalities was consistent with the position of thrombosis.A score of risk factors could provide the thrombotic information of coronary aneurysms,which might be helpful for long-term clinical management of KD patients.展开更多
Background The prevalence of congenital diaphragmatic hernia(CDH)varies across countries,with limited information available on its epidemiology in China.Our study aimed to investigate the prevalence,time trends,and pe...Background The prevalence of congenital diaphragmatic hernia(CDH)varies across countries,with limited information available on its epidemiology in China.Our study aimed to investigate the prevalence,time trends,and perinatal outcomes of CDH in China,as well as its associated malformations and potential associations with maternal and infant characteristics.Methods This study included all birth and CDH cases from the Chinese Birth Defects Monitoring Network between 2007 and 2019,with CDH cases classified as either isolated or associated.We employed the joinpoint regression model to calculate the trends of prevalence and the annual percent change,with Poisson regression used for adjusted prevalence rate ratios.A P value≤0.05 was considered statistically significant.Results A total of 4397 CDH cases were identified among 24,158,029 births in the study period,yielding prevalence rates of 1.82,1.13 and 0.69 per 10,000 for overall,isolated,and associated CDH,respectively.The prevalence of each type of CDH increased over time.The prevalence of overall CDH varied significantly by infant sex(male vs.female,1.91/10,000 vs.1.63/10,000),maternal residence(urban vs.rural,2.13/10,000 vs.1.45/10,000),maternal age(<20 years,1.31/10,000;20-24 years,1.63/10,000;25-29 years,1.80/10,000;30-34 years,1.87/10,000;≥35 years,2.22/10,000),and geographic region(central,1.64/10,000;east,2.45/10,000;west,1.37/10,000).Cardiovascular anomalies were the most common malformations associated with CDH.Infants with associated CDH had a higher risk of premature birth and perinatal death than those with isolated CDH.Conclusion The increasing prevalence and high perinatal mortality rate of CDH highlight the need for further etiological,epidemiological,and clinical studies among the Chinese population.展开更多
Background:Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus(T2DM)conferred on patients a broader tendency for complications beyond vascular ones,a comprehensive analysis of patterns...Background:Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus(T2DM)conferred on patients a broader tendency for complications beyond vascular ones,a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.Method:We prospectively studied 1777 early-onset(age at diagnosis≤45 years)and 35889 late-onset(>45 years)T2DM patients with matched unexposed individuals from the UK Biobank.Diabetes-specific and-related complications were examined using phenomewide association analysis,with patterns identified by comorbidity network analysis.We also evaluated the effect of lifestyle modifications and glycemic control on complication development.Results:The median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years,respectively.Compared to late-onset T2DM patients,patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs[hazard ratio(HR)3.46 vs.1.72],the endocrine/metabolic system(HR 3.08 vs.2.01),and the neurological system(HR 2.70 vs.1.81).Despite large similarities in comorbidity patterns,a more complex and well-connected network was observed for early-onset T2DM.Furthermore,while patients with early-onset T2DM got fewer benefits(12.67%reduction in pooled HR for all studied complications)through fair glycemic control(median HbA1c≤53 mmol/mol)compared to late-onset T2DM patients(18.01%reduction),they seemed to benefit more from favorable lifestyles,including weight control,healthy diet,and adequate physical activity.Conclusions:Our analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM.Aggressive glucose-lowering intervention,complemented by lifestyle modifications,are feasible strategies for controlling early-onset T2DM-related complications.展开更多
In this study, the evolution of C60F18 molecules on a Cu（001） surface was studied by means of scanning tunneling microscopy and density functional theory calculations. The results showed that fluorinated fuUerenes ...In this study, the evolution of C60F18 molecules on a Cu（001） surface was studied by means of scanning tunneling microscopy and density functional theory calculations. The results showed that fluorinated fuUerenes （tortoise-shaped polar C60F18） decay on Cu（001） surfaces by a step-by-step detachment of F atoms from the C60 cage. The most favorable adsorption configuration was realized when the F atoms of C60F18 pointed towards the Cu surface and six F atoms were detached from it. The results also showed that a further decay of C60F12 molecules strongly depended on the initial C60F18 coverage. The detached F atoms initially formed a two-dimensional （2D） gas phase which then slowly transformed into F-induced surface structures. The degree of contact between the C60F12 molecules and the Cu（001） surface depended on the density of the 2D gas phase. Hence, the life-time of fluorinated fullerenes was determined by the density of the 2D gas phase, which was affected by the formation of new F-induced structures and the decay of C60F12 molecules.展开更多
Background:Tyrosine phosphorylation of intracellular proteins is a posttranslational modification that plays a regulatory role in signal transduction during cellular events.Dephosphorylation of signal transduction pro...Background:Tyrosine phosphorylation of intracellular proteins is a posttranslational modification that plays a regulatory role in signal transduction during cellular events.Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases(PTPs)contributed their role as a convergent node to mediate cross-talk between signaling pathways.In the context of cancer,PTP-mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy.This is achieved by the promotion of constitutive activation of growth-stimulatory signaling pathways or modulation of the immune-suppressive tumor microenvironment.Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors,reversing drug resistance that was responsible for clinical failures during cancer therapy.Areas covered:This review aimed to elaborate recent insights that supported the involvement of PTP-mediated pathways in the development of resistance to targeted therapy and immune-checkpoint therapy.Expert opinion:This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long-term tumor regression.Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced-stage tumors.展开更多
Our study sought to investigate the blood flow pattern in the superior vena cava(SVC)of healthy adults and to describe the development and characteristics of the flow pattern using 4D flow magnetic resonance imaging(M...Our study sought to investigate the blood flow pattern in the superior vena cava(SVC)of healthy adults and to describe the development and characteristics of the flow pattern using 4D flow magnetic resonance imaging(MRI).4D flow MRI data with full coverage of SVC and brachiocephalic veins(BVs)were acquired with a 3-Testa MRI in thirty healthy adults(age:28.70±9.09).Hemodynamic parameters in the SVC,including velocity,velocity vector,flow visualization(pathlines,streamlines),flow waveform and energy loss,were obtained with specialized commercial post-processing software based on 4D flow MRI data.This study found that:(1)The SVC has a pulsating flow waveform with double peaks.(2)Based on BVs flow of the SVC pathline visualization,flow patterns could be divided into three development types:twining(n=14),untwining(n=)and no helical flow(n=7).(3)With the decreasing blood velocity,helical flow areas tended to gradually extend.(4)There were no significant differences in most hemodynamic parameters among the three types.The exploration of the blood flow characteristics of normal SVC may be the first step for capturing pathogenic features before the patients develop symptoms with a certain positive significance.The potential physiological significance of these phenomena deserves more exploration in future studies.展开更多
Despite the established associations between sleep-related traits and major diseases,comprehensive assessment on affected disease modules and their genetic determinants is lacking.Using multiple correspondence analysi...Despite the established associations between sleep-related traits and major diseases,comprehensive assessment on affected disease modules and their genetic determinants is lacking.Using multiple correspondence analysis and the k-means clus-tering algorithm,235,826 eligible participants were clustered into distinct unfavorable sleep patterns[short sleep duration(n=10,073),snoring(22,419),insomnia(102,771),insomnia and snoring(62,909)]and favorable sleep pattern groups(37,654).The associations of unfavorable sleep patterns with 134 diseases were estimated using Cox regression models;and comorbidity network analyses were applied for disease module identification.Genetic determinants associated with each disease module were identified by genome-wide association studies(GWAS).During an average follow-up of 10.80 years,unfavorable sleep patterns featured by‘short sleep duration’,‘snoring’,‘insomnia’,and‘insomnia and snoring’were associated with increased risk of 0,9,10,and 19 diseases,respectively.Furthermore,comorbidity network analyses categorized these affected diseases into three disease modules,characterized by predominant diseases related to digestive system,circulatory and endocrine systems(snoring-related patterns only),and musculoskeletal system(insomnia-related patterns only).Using the number of affected diseases,as an index of a person's susceptibility to each disease module[i.e.,susceptible score(SS)],GWAS analyses identified five,one,and three significant loci associated with the residual SS of these aforementioned disease modules,respectively,which mapped to several potential biological pathways,including those related to hormone regulation and catecholamine uptake.In conclusion,individuals with unfavorable sleep patterns,particularly snoring and insomnia,had increased risk of multiple diseases.The identification of three major disease modules with their relevant genetic determinants may facilitate strategy development for precision prevention of future health decline.展开更多
基金support from the National Science Foundation (Grant CMMI-1934300)Defense Advanced Research Projects Agency (DARPA) under the Physics of Artificial Intelligence (PAI) program (Grant HR00111890034)partial funding support by graduate fellowship from China Scholarship Council (CSC) in this effort
文摘In many applications,flow measurements are usually sparse and possibly noisy.The reconstruction of a high-resolution flow field from limited and imperfect flow information is significant yet challenging.In this work,we propose an innovative physics-constrained Bayesian deep learning approach to reconstruct flow fields from sparse,noisy velocity data,where equationbased constraints are imposed through the likelihood function and uncertainty of the reconstructed flow can be estimated.Specifically,a Bayesian deep neural network is trained on sparse measurement data to capture the flow field.In the meantime,the violation of physical laws will be penalized on a large number of spatiotemporal points where measurements are not available.A non-parametric variational inference approach is applied to enable efficient physicsconstrained Bayesian learning.Several test cases on idealized vascular flows with synthetic measurement data are studied to demonstrate the merit of the proposed method.
文摘Considering the complexity of the networks and the need for telecommunication operators （Telco） to present innovations to their clients, the quickest possible, one of the solutions for this complexity could be to centralize its configuration. Thus the SDN （software-defmed networking） concept may be an important solution. This paper suggests the implementation of a tool to support the development and testing of networks and services before they are put into production. The use of a tool that simplifies the configuration of a network service makes the networks and services to be less susceptible to errors and failures by those who set them up, thus allowing telecom operators, among others, to be able to create new services, improve the monitorization of their human resources and, above all, improve their fmancial results. In the end, success will be achieved because with a simple interaction and basic knowledge we are able to manage network services.
文摘Tooth decay affects most of the population in developed countries. The multifactorial etiology of the disease includes multiple bacterial species, S. mutans is the main pathogen associated with the disease. This bacterium adheres to the tooth surface and allows the colonization of other microorganisms resulting in dental biofilm. Several therapeutic agents are available to treat or prevent tooth decay, but none, with the exception of fluoride, has significantly influenced the disease’s global burden. Moreover, the probable development of resistance of microorganisms to existing antibacterial agents and the scarcity of good antimicrobial agents motivates this effort for innovation. The detailed knowledge obtained in recent years on the S. mutans allowed the identification of potential targets in this microorganism, enabling the development of specific drugs to combat tooth decay. Thus, the identification of potential targets in these pathogens is the first step in the discovery process of new therapeutic agents. Currently, the experimental assays used for this purpose are expensive and time consuming. In contrast, bioinformatics methods to predict drug targets are cheap, quick and workaday in the biotechnology. This article will review the potential drug targets in S. mutans, as well as the bioinformatics methods used to identify these targets and effective drugs for specific pharmacological treatment of dental caries.
基金National Natural Science Foundation of China,Grant/Award Number:72204169Department of Science and Technology of Sichuan Province,Grant/Award Number:2021YFS0393。
文摘Background:Studies have shown that heart rate variability(HRV)is a predictor of the prognosis of cardiovascular diseases.Contact heartbeat monitoring equipment is widely used,especially in hospitals,and benefits from the rapidity and accuracy of the detection of physiological health indicators.However,long-term contact with equipment has many adverse effects.The purpose of this study was to improve the accuracy of HRV detection via noncontact equipment,thus enabling HRV to be assessed in various scenarios.Methods:A novel deep learning approach was proposed for measuring heartbeats through camera videos.First,we performed facial segmentation and divided the face into 16 grid cells with different light balance scores.After the trend is filtered by the Hamming window,a transformer-based neural network is used to further filter the signal.Finally,heart rate(HR)and HRV are estimated.Results:We used 1 million synthetic data points for pretraining and a public dataset in combination with a dataset that we constructed for task training.The final results were obtained on a test dataset that we constructed.The accuracy for HR with a low light balance score(0.867-0.983)was greater than that with a high score(0.667-0.750).Our method had higher accuracy in estimating HR than traditional filtering methods(0.167-0.417)and state-of-the-art neural network filtering methods(0.783-0.917)did.The root mean square error of the HRV from the time domain was the lowest,and the correlation index score was the highest for the HRV from the frequency domain estimated by our method compared with those estimated by two neural networks.Conclusions:Light balance,large sample training,and two-stage training can improve the accuracy of HRV estimation.
基金Supported by National Cancer InstituteCairo University,Cairo,Egypt
文摘AIM: To develop a mathematical model for the early detection of hepatocellular carcinoma (HCC) with a panel of serum proteins in combination with α-fetoprotein (AFP).METHODS: Serum levels of interleukin (IL)-8, soluble intercellular adhesion molecule-1 (sICAM-1), soluble tumor necrosis factor receptor II (sTNF-RII), proteasome, and β-catenin were measured in 479 subjects categorized into four groups: (1) HCC concurrent with hepatitis C virus (HCV) infection (n = 192); (2) HCV related liver cirrhosis (LC) (n = 96); (3) Chronic hepatitis C (CHC) (n = 96); and (4) Healthy controls (n = 95). The R package and different modules for binary and multi-class classifiers based on generalized linear models were used to model the data. Predictive power was used to evaluate the performance of the model. Receiver operating characteristic curve analysis over pairs of groups was used to identify the best cutoffs differentiating the different groups.RESULTS: We revealed mathematical models, based on a binary classifier, made up of a unique panel of serum proteins that improved the individual performance of AFP in discriminating HCC patients from patients with chronic liver disease either with or without cirrhosis. We discriminated the HCC group from the cirrhotic liver group using a mathematical model (-11.3 + 7.38 × Prot + 0.00108 × sICAM + 0.2574 × β-catenin + 0.01597 × AFP) with a cutoff of 0.6552, which achieved 98.8% specificity and 89.1% sensitivity. For the discrimination of the HCC group from the CHC group, we used a mathematical model [-10.40 + 1.416 × proteasome + 0.002024 × IL + 0.004096 × sICAM-1 + (4.251 × 10<sup>-4</sup>) × sTNF + 0.02567 × β-catenin + 0.02442 × AFP] with a cutoff 0.744 and achieved 96.8% specificity and 89.7% sensitivity. Additionally, we derived an algorithm, based on a binary classifier, for resolving the multi-class classification problem by using three successive mathematical model predictions of liver disease status.CONCLUSION: Our proposed mathematical model may be a useful method for the early detection of different statuses of liver disease co-occurring with HCV infection.
基金funded by grants from the Natural Science Foundation of Guangdong Province,China(No.2023A1515010148)the Postdoctoral Fellowship Program of CPSF(No.GZC20241143)+2 种基金the China Postdoctoral Science Foundation(No.2024M752202)the National Natural Youth Science Foundation of China(No.32100927)the National Natural Science Foundation of China(No.81970481).
文摘Biomolecular aggregation within cellular environments via liquid-liquid phase separation(LLPS)spontaneously forms droplet-like structures,which play pivotal roles in diverse biological processes.These structures are closely associated with a range of diseases,including neurodegenerative disorders,cancer and infectious diseases,highlighting the significance of understanding LLPS mechanisms for elucidating disease pathogenesis,and exploring potential therapeutic interventions.In this review,we delineate recent advancements in LLPS research,emphasizing its pathological relevance,therapeutic considerations,and the pivotal role of bioinformatic tools and databases in facilitating LLPS investigations.Additionally,we undertook a comprehensive analysis of bioinformatic resources dedicated to LLPS research in order to elucidate their functionality and applicability.By providing comprehensive insights into current LLPS-related bioinformatics resources,this review highlights its implications for human health and disease.
基金supported by grants fiom the National Natural Science and Technology Major Project(No.2018ZX10201002)China Postdoctoral Science Foundation(No.2020M673221)the Fundamental Research Funds for the Central Universities(No.2020SCU12056).
文摘Background:Anthrax is a zoonotic infectious disease caused by Bacillus anthracis.Investigating the spatiotemporal characteristics of anthrax and the impact of meteorological factors on the incidence of anthrax is helpful for the prevention and control of anthrax.Methods:At first,we applied the Granger causality test to explore the spatiotemporal characteristics of anthrax transmission between the counties and cities of Gannan Tibetan Autonomous Prefecture,Gansu Province of China.Then,we constructed three generalized linear models to analyze the impact of meteorological factors on the monthly number of anthrax cases in Gannan Tibetan Autonomous Prefecture.Finally,we developed an easy-to-use online web server that integrates the above functions.Results:This study developed an online service website(ASTM,http://www.combio-lezhang.online/anthrax/index.html)for the analysis and visualization of anthrax,which not only can investigate the correlation of anthrax among different regions in Gannan Tibetan Autonomous Prefecture,but also can analyze the correlation between meteorological factors and!the number of anthrax cases.Conclusions:Our study not only explored spatiotemporal characteristics of anthrax transmission,but also analyzed the impact of seven meteorological factors on the monthly number of anthrax cases.Meanwhile,the online service website which integrates the above functions is useful for the prevention and control of anthrax.
基金supported by the National Natural Science Foundation of China(T2341022,T2350003,T2341007,12322119,62172164,12271180,12131020,and 31930022)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38040400)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2024A1515011797)the Special Fund for Science and Technology Innovation Strategy of Guangdong Province(2021B0909050004,2021B0909060002)the Major Key Project of Peng Cheng Laboratory(PCL2021A12)JST Moonshot R&D(JPMJMS2021).
文摘Making time-series forecasting in a robust way is a difficult task only based on the observed data of a non-linear system.In this work,a neural network computing framework,the spatiotemporal information conver-sion machine(STICM),was developed to efficiently and accurately render a forecasting of a time series by employing a spatial-temporal information(STI)transformation.STICM combines the advantages of both the STI equation and the temporal convolutional network,which maps the high-dimensional/spatial data to the future temporal values of a target variable,thus naturally providing the forecasting of the target variable.From the observed variables,the STICM also infers the causal factors of the target variable in the sense of Granger causality,which are in turn selected as effective spatial information to improve the robustness of time-series forecasting.The STICM was successfully applied to both benchmark systems and real-world datasets,all of which show superior and robust performance in timeseries forecasting,even when the data were perturbed by noise.From both theoretical and computational viewpoints,the STICM has great potential in practical applications in artificial intelligence or as a model-free method based only on the observed data,and also opens a new way to explore the observed high-dimensional data in a dynamical manner for machine learning.
基金supported by grants from the 1.3.5 project for disciplines of excellence from West China Hospital of Sichuan University(No.ZYGD23015)National Natural Science Foundation of China(No.32100927)+1 种基金Sichuan Science and Technology Program(No.2023NSFSC1598)Chengdu Municipal Science and Technology Bureau Program(No.2022-YF05-01538-SN).
文摘Background:Chronic kidney disease(CKD)is a global health issue,with renal fibrosis being a common pathway in CKD development.Histone modification plays crucial roles in transcriptional regulation,but their pathological functions and mechanisms in CKD are not well understood.Methods:We utilized chromatin immunoprecipitation with next-generation DNA sequencing(ChIP-seq)and RNA-seq to evaluate the states and functions of H3 lysine 27 acetylation(H3K27ac)and H3 lysine 4 trimethylation(H3K4me3)in kidney of CKD mice.We identified epigenetic factors regulating H3K27ac through motif analysis.Expression of activating transcription factor 3(ATF3)in CKD mouse models and patients’kidneys was validated via immunofluorescence staining or Western blot.We further generated the Atf3 deficient(Atf3^(-/-)) mice to explore its effect in kidney function and fibrosis.ChIP-seq of H3K27ac from Atf3-/-CKD mice was employed to validate ATF3’s regulatory effects.We explored how ATF3 maintains the state of H3K27ac by integrating the data sources from multiple databases.Results:The states of H3K27ac and H3K4me3 were changed during CKD,and positively correlated with differential gene expression.ATF3 was highly expressed in kidney of both patients and mice with CKD,and co-localized with H3K27ac in genome,epigenetically regulating H3K27ac state.Atf3 deficient in CKD mice significantly ameliorated kidney dysfunction and fibrotic phenotype,and reduced H3K27ac levels at the ATF3 binding sites.Mechanically,ATF3 may facilitate H3K27ac maintenance by corrodinating histone acetyltransferase(HATs)-associated regulatory machinery during CKD.Conclusion:ATF3 promotes kidney injury and fibrosis in CKD by maintaining the state of H3k27ac via coordinating HATs regulatory machinery.
基金supported by grants from the Sichuan Science and Technology Program(No.2024NSFSC1489)the National Natural Science Foundation of China(No.82101653)+8 种基金Major Science&Technology Program of Sichuan Province(No.2022ZDZX0021)the National Clinical Research Center for Geriatric,West China Hospital,Sichuan University(No.Z2024JC008)the National Natural Science Foundation of China(No.92248304)“Project of Max Cynader Academy of Brain Workstation,WCHSCU”(No.HXYS19005)“Sichuan Province science and technology innovation base project”(No.2023ZYD0173)the Postdoctor Research Fund of West China Hospital,Sichuan University(No.2024HXBH154)the State Key Laboratory of Robotics(No.2023-O07)Sichuan Province science and technology innovation base project(No.2023ZYD0173)Sichuan Provincial Regional Innovation Cooperation Project(No.2024YFHZ0072).
文摘To the Editor:Sarcopenia,defined by the European Working Group on Sarcopenia in Older People(EWGSOP)as the presence of both low muscle mass and low muscle strength or performance,has emerged as a critical public health concern in aging populations.[1]Moreover,sarcopenic obesity(SO),first characterized by Baumgartner as the coexistence of sarcopenia and obesity,was another high-risk geriatric syndrome.[2]Obesity and sarcopenia often coexist in the aging population and exhibit strong bidirectional associations.A recent meta-analysis encompassing 106 clinical studies(N=167,151 older individuals)reported a pooled SO prevalence of 9%in both sexes.[3]Importantly,it revealed a 51%increased risk of all-cause mortality(pooled hazard ratio[HR]=1.51,95%confidence intetal[CI]1.14–2.02,P<0.001)among individuals with SO compared to their healthy counterparts.[3]Given its adverse health implications,emerging research underscores the need to approach SO as a distinct,multifactorial phenotype.Consequently,identifying robust predictors of SO is imperative for targeted interventions.
基金National Safe Haven,as part of the Data and Connectivity National Core Study,led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation(grant ref:MC_PC_20029 and MC_PC_20058)supported by grants from the National Natural Science Foundation of China(32270438 to C.D.,32170498 to S.S.L.,32400574 to X.L.)+6 种基金the National Key R&D Program of China(2021YFF0702000 to C.D.)the National Science and Technology Major Project(2023ZD0506800 to C.D.)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYYC21011 to C.D.)the National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(Z2023JC003 to C.D.)the Science and Technology Department of Sichuan Province(2022YFH0116 to C.D.)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD to C.D.)the China Postdoctoral Science Foundation(2024M752193 to H.D.C.,2024M752198 to X.L.),the Sichuan Science and Technology Program(2025ZNSFSC0984 to H.D.C.,2024NSFSC1178 to X.L.,2023NSFSC2420 to H.P.Z.).
文摘Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic disorder characterized by gastrointestinal inflammation.Cigarette smoke is a well-established risk factor for the development and exacerbation of CD while exerting a paradoxical protective effect against the onset of UC.The exact mechanisms by which cigarette smoke influences IBD,as well as the opposite effects in UC and CD,have long remained unexplained.Here,we demonstrated the detrimental impact of cigarette smoke on CD progression while highlighting its beneficial effects on UC,as evidenced by analyses of human sample data.Mouse models of CD and UC exposed to cigarette smoke presented phenotypes consistent with those observed in human disease.GPR15,previously reported to direct regulatory T(Treg)cell colon homing,was upregulated in the colon tissues of both chemically induced colitis models after smoke exposure.Importantly,Gpr15 deletion ameliorated smoke-induced CD while increasing UC severity in mice.Furthermore,our study revealed that cigarette smoke mediated GPR15 to amplify colonic T helper type 17(Th17)cell populations,thereby worsening the adverse effects of smoking on CD in mouse models.Moreover,cigarette smoke induced an increase in Treg cells through GPR15,which contributed to mitigating its impact on UC in mouse models.Moreover,in cigarette smoke-exposed CD and UC model mice,C57BL/6JGpt-Tg(human GPR15)transgenic mice presented phenotypes opposite those of Gpr15-deficient mice.Overall,our study offers mechanistic insights into the role of cigarette smokeinduced GPR15+T cells in mediating the divergent effects of smoking on UC and CD.
基金supported by National Health Commission of China(23H1094 and 23H1095).
文摘Background Birth defects constitute a significant public health issue worldwide,yet there is a lack of comprehensive population-based data for the Chinese population.Methods We analyzed data from the China National Population-based Birth Defects Surveillance System from 2007 to 2021,we calculated the prevalence rates of selected birth defects,stratified by maternal residence,geographic region,maternal age,and infant sex.The Joinpoint regression model was utilized to assess trends and annual percent changes in prevalence.Results From 2007 to 2021,significant downward trends in prevalence were observed for neural tube defects(NTDs),hydrocephalus,cleft lip with or without palate(CL/P),limb reduction defects(LRD),omphalocele,Down syndrome,and tetralogy of Fallot(TOF).Conversely,upward trends were identified for hypospadias,cleft palate(CP),microtia/anotia,polydactyly,syndactyly,ventricular septal defect(VSD),atrial septal defect/patent foramen ovale(ASD/PFO),and patent ductus arteriosus(PDA).Younger mothers exhibited a higher prevalence of hydrocephalus,gastroschisis,CL/P,and polydactyly,while anotia/microtia,Down syndrome,and congenital heart diseases(CHDs)were more common in mothers aged 35 years or older.Significant variations in the prevalence of anencephalus,spina bifida,CL/P,anorectal atresia/stenosis,hypospadias,polydactyly,syndactyly,VSD,ASD/PFO,and PDA were found across different maternal residences and geographic regions.Conclusion This study highlights the diverse trends and prevalence patterns of major birth defects,underscoring the necessity for defect-specific public health interventions.
基金Zeng X was supported by the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYJC18010)funding was also obtained fromthe National Natural Science Foundation of China(No.81900614)+1 种基金the Science and Technology Department of Sichuan Province(No.2021YF0035)the Chengdu Science and TechnologyBureau(No.2020-YF09-00117-GX).
文摘Background:The risk for chronic kidney disease(CKD)is influenced by genetic predisposition,sex,and lifestyle.Previous research indicates that coffee is a potentially protective factor in CKD.The current study aims to investigate whether sex disparity exists in the coffee–CKD association,and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.Methods:A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study,which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model.Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data(n=255,343).Analyses stratified by genetic predisposition,comorbidities,and sex hormones were performed.Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results.Results:Coffee was inversely associated with CKD in a dose-dependent manner.The effects of coffee did not differ across different strata of genetic risk for CKD,but were more evident among slower genetically predicted caffeine metabolizers.Significant sex disparity was observed(P value for interaction=0.013),in that coffee drinking was only associated with the risk reduction of CKD in females.Subgroup analysis revealed that testosterone and sex hormone-binding globulin(SHBG),but not estradiol,modified the coffee–CKD association.Conclusions:In addition to the overall inverse coffee–CKD association that was observed in the general population,we could also establish that a sex disparity existed,in that females were more likely to experience the benefit of the association.Testosterone and SHBG may partly account for the sex disparity.
基金This work was supported by the National Natural Science Foundation of China[12072214]the Key Research&Development Project of Science and Technology of Sichuan Province[2021YFS0142]1⋅3⋅5 project for disciplines of excellence,West China Hospital,Sichuan University[ZYGD18013].
文摘Kawasaki Disease(KD)patients with co-occurrent coronary artery aneurysms(CAAs)are prone to thrombosis.This study explores the thrombotic influence of morphology and hemodynamics in KD patients with CAAs.Patient-specific computed tomography angiogram images of 9 patients were used to rebuild coronary models(including 23 aneurysms;10 in thrombosed group,and 13 in non-thrombosed group)and perform computational simulations to obtain the hemodynamic parameters.The thrombosed and non-thrombosed groups were compared in terms of six parameters,namely,the maximum diameter(D_(max)),aspect ratio(R_(l/d)),shape,time-averaged wall shear stress(TAWSS),oscillatory shear index(OSI),and relative residence time(RRT).The results showed that:(1)In thrombosed aneurysms,there were several vortex structures(eddy zone),of which the position changed continuously in a cardiac cycle.In non-thrombosed aneurysms,the streamlines showed a large streaming zone.(2)Abnormal hemodynamic areas of aneurysms with thrombosis tended to appear in the same region(especially the proximal and near myocardial side of aneurysms).(3)In the non-thrombosed group,there was a correlation between the morphological and hemodynamic parameters.In thrombosed aneurysms,the flow pulsatility has a significant impact on the flow pattern.The thrombosed coronary aneurysms exhibited more risk factors and the co-location of hemodynamic abnormalities was consistent with the position of thrombosis.A score of risk factors could provide the thrombotic information of coronary aneurysms,which might be helpful for long-term clinical management of KD patients.
基金supported by National Health Commission of China.
文摘Background The prevalence of congenital diaphragmatic hernia(CDH)varies across countries,with limited information available on its epidemiology in China.Our study aimed to investigate the prevalence,time trends,and perinatal outcomes of CDH in China,as well as its associated malformations and potential associations with maternal and infant characteristics.Methods This study included all birth and CDH cases from the Chinese Birth Defects Monitoring Network between 2007 and 2019,with CDH cases classified as either isolated or associated.We employed the joinpoint regression model to calculate the trends of prevalence and the annual percent change,with Poisson regression used for adjusted prevalence rate ratios.A P value≤0.05 was considered statistically significant.Results A total of 4397 CDH cases were identified among 24,158,029 births in the study period,yielding prevalence rates of 1.82,1.13 and 0.69 per 10,000 for overall,isolated,and associated CDH,respectively.The prevalence of each type of CDH increased over time.The prevalence of overall CDH varied significantly by infant sex(male vs.female,1.91/10,000 vs.1.63/10,000),maternal residence(urban vs.rural,2.13/10,000 vs.1.45/10,000),maternal age(<20 years,1.31/10,000;20-24 years,1.63/10,000;25-29 years,1.80/10,000;30-34 years,1.87/10,000;≥35 years,2.22/10,000),and geographic region(central,1.64/10,000;east,2.45/10,000;west,1.37/10,000).Cardiovascular anomalies were the most common malformations associated with CDH.Infants with associated CDH had a higher risk of premature birth and perinatal death than those with isolated CDH.Conclusion The increasing prevalence and high perinatal mortality rate of CDH highlight the need for further etiological,epidemiological,and clinical studies among the Chinese population.
基金supported by 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(Grant No.ZYYC21005 to HS)by the National Natural Science Foundation of China(Grant No.81971262 to H.S.)。
文摘Background:Although cumulating evidence has suggested that early-onset type 2 diabetes mellitus(T2DM)conferred on patients a broader tendency for complications beyond vascular ones,a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.Method:We prospectively studied 1777 early-onset(age at diagnosis≤45 years)and 35889 late-onset(>45 years)T2DM patients with matched unexposed individuals from the UK Biobank.Diabetes-specific and-related complications were examined using phenomewide association analysis,with patterns identified by comorbidity network analysis.We also evaluated the effect of lifestyle modifications and glycemic control on complication development.Results:The median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years,respectively.Compared to late-onset T2DM patients,patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs[hazard ratio(HR)3.46 vs.1.72],the endocrine/metabolic system(HR 3.08 vs.2.01),and the neurological system(HR 2.70 vs.1.81).Despite large similarities in comorbidity patterns,a more complex and well-connected network was observed for early-onset T2DM.Furthermore,while patients with early-onset T2DM got fewer benefits(12.67%reduction in pooled HR for all studied complications)through fair glycemic control(median HbA1c≤53 mmol/mol)compared to late-onset T2DM patients(18.01%reduction),they seemed to benefit more from favorable lifestyles,including weight control,healthy diet,and adequate physical activity.Conclusions:Our analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM.Aggressive glucose-lowering intervention,complemented by lifestyle modifications,are feasible strategies for controlling early-onset T2DM-related complications.
文摘In this study, the evolution of C60F18 molecules on a Cu（001） surface was studied by means of scanning tunneling microscopy and density functional theory calculations. The results showed that fluorinated fuUerenes （tortoise-shaped polar C60F18） decay on Cu（001） surfaces by a step-by-step detachment of F atoms from the C60 cage. The most favorable adsorption configuration was realized when the F atoms of C60F18 pointed towards the Cu surface and six F atoms were detached from it. The results also showed that a further decay of C60F12 molecules strongly depended on the initial C60F18 coverage. The detached F atoms initially formed a two-dimensional （2D） gas phase which then slowly transformed into F-induced surface structures. The degree of contact between the C60F12 molecules and the Cu（001） surface depended on the density of the 2D gas phase. Hence, the life-time of fluorinated fullerenes was determined by the density of the 2D gas phase, which was affected by the formation of new F-induced structures and the decay of C60F12 molecules.
基金National Natural Science Foundation of China,Grant/Award Numbers:82273770,22177083Natural Science Foundation of Sichuan Province,Grant/Award Number:2022NSFSC1290+3 种基金135 Project for Disciplines of Excellence–Clinical Research Incubation ProjectWest China HospitalWest China Nursing Discipline Development Special Fund ProjectSichuan University,Grant/Award Numbers:ZYJC21016,HXHL21011。
文摘Background:Tyrosine phosphorylation of intracellular proteins is a posttranslational modification that plays a regulatory role in signal transduction during cellular events.Dephosphorylation of signal transduction proteins caused by protein tyrosine phosphatases(PTPs)contributed their role as a convergent node to mediate cross-talk between signaling pathways.In the context of cancer,PTP-mediated pathways have been identified as signaling hubs that enabled cancer cells to mitigate stress induced by clinical therapy.This is achieved by the promotion of constitutive activation of growth-stimulatory signaling pathways or modulation of the immune-suppressive tumor microenvironment.Preclinical evidences suggested that anticancer drugs will release their greatest therapeutic potency when combined with PTP inhibitors,reversing drug resistance that was responsible for clinical failures during cancer therapy.Areas covered:This review aimed to elaborate recent insights that supported the involvement of PTP-mediated pathways in the development of resistance to targeted therapy and immune-checkpoint therapy.Expert opinion:This review proposed the notion of PTP inhibition in anticancer combination therapy as a potential strategy in clinic to achieve long-term tumor regression.Ongoing clinical trials are currently underway to assess the safety and efficacy of combination therapy in advanced-stage tumors.
基金This work was supported by the Key Research&Development Project of Science and Technology of Sichuan Province(2021YFS0142)the National Natural Science Foundation of China(81601462)+1 种基金the National Natural Science Foundation of China(12072214)the 1⋅3⋅5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD18013).
文摘Our study sought to investigate the blood flow pattern in the superior vena cava(SVC)of healthy adults and to describe the development and characteristics of the flow pattern using 4D flow magnetic resonance imaging(MRI).4D flow MRI data with full coverage of SVC and brachiocephalic veins(BVs)were acquired with a 3-Testa MRI in thirty healthy adults(age:28.70±9.09).Hemodynamic parameters in the SVC,including velocity,velocity vector,flow visualization(pathlines,streamlines),flow waveform and energy loss,were obtained with specialized commercial post-processing software based on 4D flow MRI data.This study found that:(1)The SVC has a pulsating flow waveform with double peaks.(2)Based on BVs flow of the SVC pathline visualization,flow patterns could be divided into three development types:twining(n=14),untwining(n=)and no helical flow(n=7).(3)With the decreasing blood velocity,helical flow areas tended to gradually extend.(4)There were no significant differences in most hemodynamic parameters among the three types.The exploration of the blood flow characteristics of normal SVC may be the first step for capturing pathogenic features before the patients develop symptoms with a certain positive significance.The potential physiological significance of these phenomena deserves more exploration in future studies.
基金funded by UK Research and Innovation(Grant ref:MC_PC_20029 and MC_PC_20058)supported by the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYYC21005 to HS)+1 种基金the Ministry of Science and Technology of the People’s Republic of China(No.2021ZD0201900 to XT)We thank the team members involved in West China Biomedical Big Data Center for their support.
文摘Despite the established associations between sleep-related traits and major diseases,comprehensive assessment on affected disease modules and their genetic determinants is lacking.Using multiple correspondence analysis and the k-means clus-tering algorithm,235,826 eligible participants were clustered into distinct unfavorable sleep patterns[short sleep duration(n=10,073),snoring(22,419),insomnia(102,771),insomnia and snoring(62,909)]and favorable sleep pattern groups(37,654).The associations of unfavorable sleep patterns with 134 diseases were estimated using Cox regression models;and comorbidity network analyses were applied for disease module identification.Genetic determinants associated with each disease module were identified by genome-wide association studies(GWAS).During an average follow-up of 10.80 years,unfavorable sleep patterns featured by‘short sleep duration’,‘snoring’,‘insomnia’,and‘insomnia and snoring’were associated with increased risk of 0,9,10,and 19 diseases,respectively.Furthermore,comorbidity network analyses categorized these affected diseases into three disease modules,characterized by predominant diseases related to digestive system,circulatory and endocrine systems(snoring-related patterns only),and musculoskeletal system(insomnia-related patterns only).Using the number of affected diseases,as an index of a person's susceptibility to each disease module[i.e.,susceptible score(SS)],GWAS analyses identified five,one,and three significant loci associated with the residual SS of these aforementioned disease modules,respectively,which mapped to several potential biological pathways,including those related to hormone regulation and catecholamine uptake.In conclusion,individuals with unfavorable sleep patterns,particularly snoring and insomnia,had increased risk of multiple diseases.The identification of three major disease modules with their relevant genetic determinants may facilitate strategy development for precision prevention of future health decline.
