BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence r...BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.展开更多
DNA nanotubes(DNTs)with user-defined shapes and functionalities have potential applications in many fields.So far,compared with numerous experimental studies,there have been only a handful of models on the mechanical ...DNA nanotubes(DNTs)with user-defined shapes and functionalities have potential applications in many fields.So far,compared with numerous experimental studies,there have been only a handful of models on the mechanical properties of such DNTs.This paper aims at presenting a multiscale model to quantify the correlations among the pre-tension states,tensile properties,encapsulation structures of DNTs,and the surrounding factors.First,by combining a statistical worm-like-chain(WLC)model of single DNA deformation and Parsegian's mesoscopic model of DNA liquid crystal free energy,a multiscale tensegrity model is established,and the pre-tension state of DNTs is characterized theoretically for the first time.Then,by using the minimum potential energy principle,the force-extension curve and tensile rigidity of pre-tension DNTs are predicted.Finally,the effects of the encapsulation structure and surrounding factors on the tensile properties of DNTs are studied.The predictions for the tensile behaviors of DNTs can not only reproduce the existing experimental results,but also reveal that the competition of DNA intrachain and interchain interactions in the encapsulation structures determines the pre-tension states of DNTs and their tensile properties.The changes in the pre-tension states and environmental factors make the monotonic or non-monotonic changes in the tensile properties of DNTs under longitudinal loads.展开更多
Electrostatic layer-by-layer self-assembly multilayer films were successfully fabricated from C-60-ethylenediamine adduct (C-60-EDA) and DNA. Under visible light irradiation, DNA is ready to be cleaved and the films a...Electrostatic layer-by-layer self-assembly multilayer films were successfully fabricated from C-60-ethylenediamine adduct (C-60-EDA) and DNA. Under visible light irradiation, DNA is ready to be cleaved and the films are destroyed.展开更多
Understanding the dynamic assembly process of DNA nanostructures is important for developing novel strategy to design and construct functional devices.In this work,temperature-controlled dynamic light scattering(DLS)s...Understanding the dynamic assembly process of DNA nanostructures is important for developing novel strategy to design and construct functional devices.In this work,temperature-controlled dynamic light scattering(DLS)strategy has been applied to study the global assembly process of DNA origami and DNA bricks.Through the temperature dependent size and intensity profiles,the self-assembly process of various DNA nanostructures with different morphologies have been well-studied and the temperature transition ranges could be observed.Taking advantage of the DLS information,rapid preparation of the DNA origami and the brick assembly has been realized through a constant temperature annealing.Our results demonstrate that the DLS-based strategy provides a convenient and robust tool to study the dynamic process of forming hieratical DNA structures,which will benefit understanding the mechanism of self-assembly of DNA nanostructures.展开更多
Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients ...Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.展开更多
Chaos game representation （CGR） is an iterative mapping technique that processes sequences of units, such as nucleotides in a DNA sequence or amino acids in a protein, in order to determine the coordinates of their ...Chaos game representation （CGR） is an iterative mapping technique that processes sequences of units, such as nucleotides in a DNA sequence or amino acids in a protein, in order to determine the coordinates of their positions in a continuous space. This distribution of positions has two features： one is unique, and the other is source sequence that can be recovered from the coordinates so that the distance between positions may serve as a measure of similarity between the corresponding sequences. A CGR-walk model is proposed based on CGR coordinates for the DNA sequences. The CGR coordinates are converted into a time series, and a long-memory ARFIMA （p, d, q） model, where ARFIMA stands for autoregressive fractionally integrated moving average, is introduced into the DNA sequence analysis. This model is applied to simulating real CGR-walk sequence data of ten genomic sequences. Remarkably long-range correlations are uncovered in the data, and the results from these models are reasonably fitted with those from the ARFIMA （p, d, q） model.展开更多
The variational method is applied to the study of charge transfer in dry DNA by using an extended Holstein small polaron model in two cases： the site-dependent flnite-chain discrete case and the site-independent cont...The variational method is applied to the study of charge transfer in dry DNA by using an extended Holstein small polaron model in two cases： the site-dependent flnite-chain discrete case and the site-independent continuous one. The treatments in the two cases are proven to be consistent in theory and calculation. Discrete and continuous treatments of Holstein model both can yield a nonlinear equation to describe the charge migration in an actual long-range DNA chain. Our theoretical results of binding energy Eb, probability amplitude of charge carrier Ф and the relation between energy and charge-lattice coupling strength are in accordance with the available experimental results and recent theoretical calculations.展开更多
Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damag...Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.展开更多
The molecular biomechanics of DNA ejection from bacteriophage is of interest to not only fundamental biological understandings but also practical applications such as the design of advanced site-specific and controlla...The molecular biomechanics of DNA ejection from bacteriophage is of interest to not only fundamental biological understandings but also practical applications such as the design of advanced site-specific and controllable drug delivery systems. In this paper, we analyze the viscous motion of a semiflexible polymer chain coming out of a strongly confined space as a model to investigate the effects of various structure confinements and frictional resistances encountered during the DNA ejection process. The theoretically predicted relations between the ejection speed, ejection time, ejection length, and other physical parameters, such as the phage type, total genome length and ionic state of external buffer solutions, show excellent agreement with in vitro experimental observations in the literature.展开更多
Alzheimer’s disease（AD）is the most common type of dementia in elderly population.With a growing aging population not only in the United States but also in the worldwide,AD constitutes an emergent public health prob...Alzheimer’s disease（AD）is the most common type of dementia in elderly population.With a growing aging population not only in the United States but also in the worldwide,AD constitutes an emergent public health problem.展开更多
The exact solutions of the general nonlinear dynamic system in a new double-chain model of DNA are studiedkink shape excitations can be found in both the Conte's truncation expansion and the Pickering's trunca...The exact solutions of the general nonlinear dynamic system in a new double-chain model of DNA are studiedkink shape excitations can be found in both the Conte's truncation expansion and the Pickering's truncation expansion.Three types of new localized excitations, the asymmetric kink-kink excitations, the soliton-kink excitation, and thekink-soliton excitations, are found by using the Pickering's nonstandard truncation expansion.展开更多
The paper presents a multi-scale modelling approach for simulating macromolecules in fluid flows. Macromolecule transport at low number densities is frequently encountered in biomedical devices, such as separators, de...The paper presents a multi-scale modelling approach for simulating macromolecules in fluid flows. Macromolecule transport at low number densities is frequently encountered in biomedical devices, such as separators, detection and analysis systems. Accurate modelling of this process is challenging due to the wide range of physical scales involved. The continuum approach is not valid for low solute concentrations, but the large timescales of the fluid flow make purely molecular simulations prohibitively expensive. A promising multi-scale modelling strategy is provided by the meta-modelling approach considered in this paper. Meta-models are based on the coupled solution of fluid flow equations and equations of motion for a simplified mechanical model of macromolecules. The approach enables simulation of individual macromolecules at macroscopic time scales. Meta-models often rely on particle-corrector algorithms, which impose length constraints on the mechanical model. Lack of robustness of the particle-corrector algorithm employed can lead to slow convergence and numerical instability. A new FAst Linear COrrector （FALCO） algorithm is introduced in this paper, which significantly improves computational efficiency in comparison with the widely used SHAKE algorithm. Validation of the new particle corrector against a simple analytic solution is performed and improved convergence is demonstrated for ssDNA motion in a lid-driven micro-cavity.展开更多
Environmental contamination of food is a worldwide public health problem. Folate mediated one- carbon metabolism plays an important role in epigenetic regulation of gene expression and mutagenesis. Many contaminants i...Environmental contamination of food is a worldwide public health problem. Folate mediated one- carbon metabolism plays an important role in epigenetic regulation of gene expression and mutagenesis. Many contaminants in food cause cancer through epigenetic mechanisms and/or DNA instability i.e. default methylation of uracil to thymine, subsequent to the decrease of 5-methylte- trahydrofolate (5 mTHF) pool in the one-carbon metabolism network. Evaluating consequences of an exposure to food contaminants based on systems biology approaches is a promising alternative field of investigation. This report presents a dynamic mathematical modeling for the study of the alteration in the one-carbon metabolism network by environmental factors. It provides a model for predicting “the impact of arbitrary contaminants that can induce the 5 mTHF deficiency. The model allows for a given experimental condition, the analysis of DNA methylation activity and dumping methylation in the de novo pathway of DNA synthesis.展开更多
A three-dimensional dynamic model for nano/micro-fabrications of silicon was presented. With the developed model, the fabrication process of silicon on nothing（SON） structure was quantitatively investigated. We empl...A three-dimensional dynamic model for nano/micro-fabrications of silicon was presented. With the developed model, the fabrication process of silicon on nothing（SON） structure was quantitatively investigated. We employ a diffuse interface model that incorporates the mechanism of surface diffusion. The mechanism of the fabrication is systematically integrated for high reliability of computational analysis. A semi-implicit Fourier spectral scheme is applied for high efficiency and numerical stability. Moreover, the theoretical analysis provides the guidance that is ordered by the fundamental geometrical design parameters to guide different fabrications of SON structures. The performed simulations suggest a substantial potential of the presented model for a reliable design technology of nano/micro-fabrications.展开更多
BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition an...BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition and multi-target stool DNA(MT-sDNA)test in the diagnosis of CRC.METHODS We assessed the performance of the MT-sDNA test based on a hospital clinical trial.The intestinal microbiota was tested using 16S rRNA gene sequencing.This case-control study enrolled 54 CRC patients and 51 healthy controls.We identified biomarkers of bacterial structure,analyzed the relationship between different tumor markers and the relative abundance of related flora components,and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size,redundancy analysis,and random forest analysis.RESULTS MT-sDNA was associated with Bacteroides.MT-sDNA and carcinoembryonic antigen(CEA)were positively correlated with the existence of Parabacteroides,and alpha-fetoprotein(AFP)was positively associated with Faecalibacterium and Megamonas.In the random forest model,the existence of Streptococcus,Escherichia,Chitinophaga,Parasutterella,Lachnospira,and Romboutsia can distinguish CRC from health controls.The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%,with a sensitivity and specificity of 98.1%and 92.3%,respectively.CONCLUSION There is a positive correlation of MT-sDNA,CEA,and AFP with intestinal microbiome.Eight biomarkers including six genera of gut microbiota,MT-sDNA,and CEA showed a prominent sensitivity and specificity for CRC prediction,which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.展开更多
文摘BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.
基金Project supported by the National Natural Science Foundation of China(Nos.12172204,11772182,11272193,and 10872121)the Program of Shanghai Municipal Education Commission(No.2019-01-07-00-09-E00018)the Natural Science Foundation of Shanghai of China(No.22Z00142)。
文摘DNA nanotubes(DNTs)with user-defined shapes and functionalities have potential applications in many fields.So far,compared with numerous experimental studies,there have been only a handful of models on the mechanical properties of such DNTs.This paper aims at presenting a multiscale model to quantify the correlations among the pre-tension states,tensile properties,encapsulation structures of DNTs,and the surrounding factors.First,by combining a statistical worm-like-chain(WLC)model of single DNA deformation and Parsegian's mesoscopic model of DNA liquid crystal free energy,a multiscale tensegrity model is established,and the pre-tension state of DNTs is characterized theoretically for the first time.Then,by using the minimum potential energy principle,the force-extension curve and tensile rigidity of pre-tension DNTs are predicted.Finally,the effects of the encapsulation structure and surrounding factors on the tensile properties of DNTs are studied.The predictions for the tensile behaviors of DNTs can not only reproduce the existing experimental results,but also reveal that the competition of DNA intrachain and interchain interactions in the encapsulation structures determines the pre-tension states of DNTs and their tensile properties.The changes in the pre-tension states and environmental factors make the monotonic or non-monotonic changes in the tensile properties of DNTs under longitudinal loads.
基金The National Natural Science Foundation of China (Grant No. 29774036 and 29904007) and PPLAS Foundation of Chinese Academy of Sciences (Grant No. 01-B-06) are gratefully acknowledged for their financial support of this work.
文摘Electrostatic layer-by-layer self-assembly multilayer films were successfully fabricated from C-60-ethylenediamine adduct (C-60-EDA) and DNA. Under visible light irradiation, DNA is ready to be cleaved and the films are destroyed.
基金supported by the National Natural Science Foundation of China(No.21971248)。
文摘Understanding the dynamic assembly process of DNA nanostructures is important for developing novel strategy to design and construct functional devices.In this work,temperature-controlled dynamic light scattering(DLS)strategy has been applied to study the global assembly process of DNA origami and DNA bricks.Through the temperature dependent size and intensity profiles,the self-assembly process of various DNA nanostructures with different morphologies have been well-studied and the temperature transition ranges could be observed.Taking advantage of the DLS information,rapid preparation of the DNA origami and the brick assembly has been realized through a constant temperature annealing.Our results demonstrate that the DLS-based strategy provides a convenient and robust tool to study the dynamic process of forming hieratical DNA structures,which will benefit understanding the mechanism of self-assembly of DNA nanostructures.
基金supported by Grants from the National Natural Science Foundation of China(Nos.81372409,81402532)the Sun Yat-sen University Clinical Research 5010 Program(No.2012011)
文摘Background: According to the 7 th edition of the American Joint Committee on Cancer(AJCC) staging system, over50% of patients with nasopharyngeal carcinoma(NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node(GTVnd) and pretreatment serum copy number of Epstein-Barr virus(EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.Methods: The medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic(ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.Results: The 5-year distant metastasis-free survival(DMFS) rates for patients with GTVnd > 18.9 vs.≤ 18.9 mL were82.2% vs. 93.2%(P < 0.001), and for patients with EBV DNA copy number > 4000 vs. < 4000 copies/mL were 83.5% vs.93.9%(P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis(both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-,moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1,87.4, and 73.8%, respectively(P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification(hazard ratio [HR],4.17; 95% confidence interval [CI] 2.34-7.59; P < 0.001).Conclusions: GTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.
基金Project supported by the National Natural Science Foundation of China (Grant No 60575038)the Natural Science Foundation of Jiangnan University,China (Grant No 20070365)
文摘Chaos game representation （CGR） is an iterative mapping technique that processes sequences of units, such as nucleotides in a DNA sequence or amino acids in a protein, in order to determine the coordinates of their positions in a continuous space. This distribution of positions has two features： one is unique, and the other is source sequence that can be recovered from the coordinates so that the distance between positions may serve as a measure of similarity between the corresponding sequences. A CGR-walk model is proposed based on CGR coordinates for the DNA sequences. The CGR coordinates are converted into a time series, and a long-memory ARFIMA （p, d, q） model, where ARFIMA stands for autoregressive fractionally integrated moving average, is introduced into the DNA sequence analysis. This model is applied to simulating real CGR-walk sequence data of ten genomic sequences. Remarkably long-range correlations are uncovered in the data, and the results from these models are reasonably fitted with those from the ARFIMA （p, d, q） model.
基金Project supported by the National Nature Science Foundation of China （Grant No 50272063） and the Foundation for Excellent Talents of Anhui Province, China （Grant No 2001Z016）.
文摘The variational method is applied to the study of charge transfer in dry DNA by using an extended Holstein small polaron model in two cases： the site-dependent flnite-chain discrete case and the site-independent continuous one. The treatments in the two cases are proven to be consistent in theory and calculation. Discrete and continuous treatments of Holstein model both can yield a nonlinear equation to describe the charge migration in an actual long-range DNA chain. Our theoretical results of binding energy Eb, probability amplitude of charge carrier Ф and the relation between energy and charge-lattice coupling strength are in accordance with the available experimental results and recent theoretical calculations.
基金Project supported by the National Natural Science Foundation of China (Grant No. 10875049)the Key Project of Chinese Ministry of Education (Grant No. 108096)the Programme of Introducing Talents of Discipline to Universities (Grant No. B08033)
文摘Taking the interaction between a DNA damage repair module, an ATM module, and a P53--MDM2 oscillation module into account, this paper presents a mathematical model of a P53 oscillation network triggered by a DNA damage signal in individual cells. The effects of the DNA damage signal and the delay time of P53-induced MDM2 expression on the behaviours of the P53 oscillation network are studied. In the oscillatory state of the P53--MDM2 oscillator, it is found that the pulse number of P53--P oscillation increases with the increase of the initial DNA damage signal, whereas the amplitude and the period of P53--P oscillation are fixed for different initial DNA damage signals, and the period numbers of P53--P oscillations decrease with the increase of time delay of MDM2 expression induced by P53. These theoretical predictions are consistent with previous experimental results. The combined negative feedback of P53--MDM2 with the time delay of P53-induced MDM2 expression causes oscillation behaviour in the P53 network.
基金supported by the National Natural Science Foundation of China (11032006, 11072094, and 11121202)the PhD Program Foundation of the Ministry of Education of China (20100211110022)+1 种基金New Century Excellent Talents in University (NCET-10-0445)supported by the National Science Foundation through grant CMMI-1028530 to Brown University
文摘The molecular biomechanics of DNA ejection from bacteriophage is of interest to not only fundamental biological understandings but also practical applications such as the design of advanced site-specific and controllable drug delivery systems. In this paper, we analyze the viscous motion of a semiflexible polymer chain coming out of a strongly confined space as a model to investigate the effects of various structure confinements and frictional resistances encountered during the DNA ejection process. The theoretically predicted relations between the ejection speed, ejection time, ejection length, and other physical parameters, such as the phage type, total genome length and ionic state of external buffer solutions, show excellent agreement with in vitro experimental observations in the literature.
基金supported by the Brazilian funding agencies:CNPq(Conselho Nacional de Desenvolvimento Científico e Tecnológico)CAPES(Coordenacao de Aperfeicoamento de Pessoal de Nível Superior)-No:5614112Student Agreement Program for post graduation–PEC-PG.
文摘Alzheimer’s disease（AD）is the most common type of dementia in elderly population.With a growing aging population not only in the United States but also in the worldwide,AD constitutes an emergent public health problem.
基金国家杰出青年科学基金，the Research Fund for the Doctoral Program of Higher Education of China，国家自然科学基金
文摘The exact solutions of the general nonlinear dynamic system in a new double-chain model of DNA are studiedkink shape excitations can be found in both the Conte's truncation expansion and the Pickering's truncation expansion.Three types of new localized excitations, the asymmetric kink-kink excitations, the soliton-kink excitation, and thekink-soliton excitations, are found by using the Pickering's nonstandard truncation expansion.
基金supported in part by the European Commission under the 6th Framework Program (Project: DINAMICS, NMP4-CT-2007-026804).
文摘The paper presents a multi-scale modelling approach for simulating macromolecules in fluid flows. Macromolecule transport at low number densities is frequently encountered in biomedical devices, such as separators, detection and analysis systems. Accurate modelling of this process is challenging due to the wide range of physical scales involved. The continuum approach is not valid for low solute concentrations, but the large timescales of the fluid flow make purely molecular simulations prohibitively expensive. A promising multi-scale modelling strategy is provided by the meta-modelling approach considered in this paper. Meta-models are based on the coupled solution of fluid flow equations and equations of motion for a simplified mechanical model of macromolecules. The approach enables simulation of individual macromolecules at macroscopic time scales. Meta-models often rely on particle-corrector algorithms, which impose length constraints on the mechanical model. Lack of robustness of the particle-corrector algorithm employed can lead to slow convergence and numerical instability. A new FAst Linear COrrector （FALCO） algorithm is introduced in this paper, which significantly improves computational efficiency in comparison with the widely used SHAKE algorithm. Validation of the new particle corrector against a simple analytic solution is performed and improved convergence is demonstrated for ssDNA motion in a lid-driven micro-cavity.
文摘Environmental contamination of food is a worldwide public health problem. Folate mediated one- carbon metabolism plays an important role in epigenetic regulation of gene expression and mutagenesis. Many contaminants in food cause cancer through epigenetic mechanisms and/or DNA instability i.e. default methylation of uracil to thymine, subsequent to the decrease of 5-methylte- trahydrofolate (5 mTHF) pool in the one-carbon metabolism network. Evaluating consequences of an exposure to food contaminants based on systems biology approaches is a promising alternative field of investigation. This report presents a dynamic mathematical modeling for the study of the alteration in the one-carbon metabolism network by environmental factors. It provides a model for predicting “the impact of arbitrary contaminants that can induce the 5 mTHF deficiency. The model allows for a given experimental condition, the analysis of DNA methylation activity and dumping methylation in the de novo pathway of DNA synthesis.
基金the National Natural Science Foundation of China(No.51775154)the ZheJiang Provincial Natural Science Foundation of China(No.LZ15E050004)
文摘A three-dimensional dynamic model for nano/micro-fabrications of silicon was presented. With the developed model, the fabrication process of silicon on nothing（SON） structure was quantitatively investigated. We employ a diffuse interface model that incorporates the mechanism of surface diffusion. The mechanism of the fabrication is systematically integrated for high reliability of computational analysis. A semi-implicit Fourier spectral scheme is applied for high efficiency and numerical stability. Moreover, the theoretical analysis provides the guidance that is ordered by the fundamental geometrical design parameters to guide different fabrications of SON structures. The performed simulations suggest a substantial potential of the presented model for a reliable design technology of nano/micro-fabrications.
基金Supported by the Medical and Health Research Project of Zhejiang Province,No.2021KY1048 and 2022KY1142Ningbo Health Young Technical Backbone Talents Training Program,No.2020SWSQNGG-02the Key Science and Technology Project of Ningbo City,No.2021Z133.
文摘BACKGROUND Colorectal cancer(CRC)is a major global health burden.The current diagnostic tests have shortcomings of being invasive and low accuracy.AIM To explore the combination of intestinal microbiome composition and multi-target stool DNA(MT-sDNA)test in the diagnosis of CRC.METHODS We assessed the performance of the MT-sDNA test based on a hospital clinical trial.The intestinal microbiota was tested using 16S rRNA gene sequencing.This case-control study enrolled 54 CRC patients and 51 healthy controls.We identified biomarkers of bacterial structure,analyzed the relationship between different tumor markers and the relative abundance of related flora components,and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size,redundancy analysis,and random forest analysis.RESULTS MT-sDNA was associated with Bacteroides.MT-sDNA and carcinoembryonic antigen(CEA)were positively correlated with the existence of Parabacteroides,and alpha-fetoprotein(AFP)was positively associated with Faecalibacterium and Megamonas.In the random forest model,the existence of Streptococcus,Escherichia,Chitinophaga,Parasutterella,Lachnospira,and Romboutsia can distinguish CRC from health controls.The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%,with a sensitivity and specificity of 98.1%and 92.3%,respectively.CONCLUSION There is a positive correlation of MT-sDNA,CEA,and AFP with intestinal microbiome.Eight biomarkers including six genera of gut microbiota,MT-sDNA,and CEA showed a prominent sensitivity and specificity for CRC prediction,which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.
