Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This...Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking.A total of 17 bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified.The KEGG pathway analysis showed that the PI3K/Akt signaling pathway,MAPK signaling pathway,AMPK signaling pathway,and nuclear factor kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi.According to molecular docking analysis,the phytochemicals of Chenpi can bind to central anti-obesity targets.Based on the ADMET analysis and network pharmacology results,tangeretin exhibited the lowest predicted toxicity and potential for anti-obesity effects.In the in vitro lipid accumulation model,tangeretin effectively suppressed the free fatty acid-induced lipid in Hep G2 cells by upregulating the PI3K/Akt/GSK3βsignaling pathway based on the result of q-PCR and Western blotting.The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi,also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.展开更多
CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identif...CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identifying protospacer adjacent motif(PAM)sequences.Due to the limitations of experimental methods,bioinformatics approaches have become essential.However,existing PAM prediction programs are limited by the small number of spacers in CRISPR-Cas systems,resulting in low accuracy.To address this,we develop PAMPHLET,a pipeline that uses homology searches to identify additional spacers,significantly increasing the number of spacers up to 18-fold.PAMPHLET is validated on 20 CRISPR-Cas systems and successfully predicts PAM sequences for 18 protospacers.These predictions are further validated using the DocMF platform,which characterizes protein-DNA recognition patterns via next-generation sequencing.The high consistency between PAMPHLET predictions and DocMF results for Cas proteins demonstrates the potential of PAMPHLET to enhance PAM sequence prediction accuracy,expedite the discovery process,and accelerate the development of CRISPR tools.展开更多
Active disturbance-rejection methods are effective in estimating and rejecting disturbances in both transient and steady-state responses.This paper presents a deep observation on and a comparison between two of those ...Active disturbance-rejection methods are effective in estimating and rejecting disturbances in both transient and steady-state responses.This paper presents a deep observation on and a comparison between two of those methods:the generalized extended-state observer(GESO)and the equivalent input disturbance(EID)from assumptions,system configurations,stability conditions,system design,disturbance-rejection performance,and extensibility.A time-domain index is introduced to assess the disturbance-rejection performance.A detailed observation of disturbance-suppression mechanisms reveals the superiority of the EID approach over the GESO method.A comparison between these two methods shows that assumptions on disturbances are more practical and the adjustment of disturbance-rejection performance is easier for the EID approach than for the GESO method.展开更多
A uniform experimental design(UED)is an extremely used powerful and efficient methodology for designing experiments with high-dimensional inputs,limited resources and unknown underlying models.A UED enjoys the followi...A uniform experimental design(UED)is an extremely used powerful and efficient methodology for designing experiments with high-dimensional inputs,limited resources and unknown underlying models.A UED enjoys the following two significant advantages:(i)It is a robust design,since it does not require to specify a model before experimenters conduct their experiments;and(ii)it provides uniformly scatter design points in the experimental domain,thus it gives a good representation of this domain with fewer experimental trials(runs).Many real-life experiments involve hundreds or thousands of active factors and thus large UEDs are needed.Constructing large UEDs using the existing techniques is an NP-hard problem,an extremely time-consuming heuristic search process and a satisfactory result is not guaranteed.This paper presents a new effective and easy technique,adjusted Gray map technique(AGMT),for constructing(nearly)UEDs with large numbers of four-level factors and runs by converting designs with s two-level factors and n runs to(nearly)UEDs with 2^(t−1)s four-level factors and 2tn runs for any t≥0 using two simple transformation functions.Theoretical justifications for the uniformity of the resulting four-level designs are given,which provide some necessary and/or sufficient conditions for obtaining(nearly)uniform four-level designs.The results show that the AGMT is much easier and better than the existing widely used techniques and it can be effectively used to simply generate new recommended large(nearly)UEDs with four-level factors.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide.Glycolysis has been demonstrated to be pivotal for the carcinogenesis of GC.AIM To develop a glycolysis-based gene signature for prognostic...BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide.Glycolysis has been demonstrated to be pivotal for the carcinogenesis of GC.AIM To develop a glycolysis-based gene signature for prognostic evaluation in GC patients.METHODS Differentially expressed genes correlated with glycolysis were identified in stomach adenocarcinoma data(STAD).A risk score was established through a univariate Cox and least absolute shrinkage and selection operator analysis.The model was evaluated using the area under the receiver operating characteristic curves.RNA-sequencing data from high-and low-glycolysis groups of STAD patients were analyzed using Cibersort algorithm and Spearman correlation to analyze the interaction of immune cell infiltration and glycolysis.Multiomics characteristics in different glycolysis status were also analyzed.RESULTS A five-gene signature comprising syndecan 2,versican,malic enzyme 1,pyruvate carboxylase and SRY-box transcription factor 9 was constructed.Patients were separated to high-or low-glycolysis groups according to risk scores.Overall survival of patients with high glycolysis was poorer.The sensitivity and specificity of the model in prediction of survival of GC patients were also observed by receiver operating characteristic curves.A nomogram including clinicopathological characteristics and the risk score also showed good prediction for 3-and 5-year overall survival.Gene set variation analysis showed that high-glycolysis patients were related to dysregulation of pancreas beta cells and estrogen late pathways,and low-glycolysis patients were related to Myc targets,oxidative phosphorylation,mechanistic target of rapamycin complex 1 signaling and G2M checkpoint pathways.Tumor-infiltrating immune cells and multiomics analysis suggested that the different glycolysis status was significantly correlated with multiple immune cell infiltration.The patients with high glycolysis had lower tumor mutational burden and neoantigen load,higher incidence of microsatellite instability and lower chemosensitivity.High glycolysis status was often found among patients with grade 2/3 cancer or poor prognosis.CONCLUSION The genetic characteristics revealed by glycolysis could predict the prognosis of GC.High glycolysis significantly affects GC phenotype,but the detailed mechanism needs to be further studied.展开更多
For prognosis and therapeutic response,colorectal cancer(CRC)patients are highly variable across stages,correlated to high inter-tumor heterogeneity at the molecular level.1 Therefore,molecular subtyping needs to be d...For prognosis and therapeutic response,colorectal cancer(CRC)patients are highly variable across stages,correlated to high inter-tumor heterogeneity at the molecular level.1 Therefore,molecular subtyping needs to be determined for stratifying patients into distinct prognostic subgroups according to tumor biology.展开更多
Wu functions are a class of positive definite compactly supported radial basis functions in terms of piecewise polynomials.They are similar to Wendland functions that came up shortly later and they still require furth...Wu functions are a class of positive definite compactly supported radial basis functions in terms of piecewise polynomials.They are similar to Wendland functions that came up shortly later and they still require further investigation.Here,we prove that the native space of a Wu function is a dense subspace of a Sobolev space and give an explicit characterization of the native spaces of Wu functions.In addition,three definitions of Wu functions are introduced and proven to be equivalent.Based on these new equivalent definitions and the so-called f-form,we can generalize the Wu functions for the even-dimensional spaces,while the original Wu functions are proven to have odd maximal possible dimensions on which they are positive definite.Such functions in even-dimensional spaces will be called the“missing Wu functions”.Furthermore,we can generalize the Wu functions to“fractional”-dimensional spaces.We call all these Wu functions the generalized Wu functions.The closed form of the generalized Wu functions is given in terms of hypergeometric functions.Finally,we prove that the Wu functions and the missing Wu functions can be written as linear combinations of the generalized Wendland functions.展开更多
In this article,we study the energy dissipation property of time-fractional Allen–Cahn equation.On the continuous level,we propose an upper bound of energy that decreases with respect to time and coincides with the o...In this article,we study the energy dissipation property of time-fractional Allen–Cahn equation.On the continuous level,we propose an upper bound of energy that decreases with respect to time and coincides with the original energy at t=0 and as t tends to∞.This upper bound can also be viewed as a nonlocal-in-time modified energy which is the summation of the original energy and an accumulation term due to the memory effect of time-fractional derivative.In particular,the decrease of the modified energy indicates that the original energy indeed decays w.r.t.time in a small neighborhood at t=0.We illustrate the theory mainly with the time-fractional Allen-Cahn equation but it could also be applied to other time-fractional phase-field models such as the Cahn-Hilliard equation.On the discrete level,the decreasing upper bound of energy is useful for proving energy dissipation of numerical schemes.First-order L1 and second-order L2 schemes for the time-fractional Allen-Cahn equation have similar decreasing modified energies,so that stability can be established.Some numerical results are provided to illustrate the behavior of this modified energy and to verify our theoretical results.展开更多
Background:Autophagy death of cancer cells is detrimental to apoptosis induced by therapeutic drugs,which promotes tumor progression to a certain extent.Increasing reports have demonstrated the regulatory role of circ...Background:Autophagy death of cancer cells is detrimental to apoptosis induced by therapeutic drugs,which promotes tumor progression to a certain extent.Increasing reports have demonstrated the regulatory role of circular RNAs(circRNAs)in autophagy.Here,we aimed to determine the role of hsa_circ_0009109 in autophagy in gastric cancer(GC).Methods:The effects of hsa_circ_0009109 on autophagy were examined using quantitative real-time polymerase chain reaction(qPCR),transmission electron microscopy,Western blot,and immunofluorescence.The mechanism of hsa_circ_0009109 regulating the miR-544a-3p/bcl-2 axis was analysed using fluorescence in situ hybridization,dual-luciferase reporter,and rescue experiments.Results:Functional testing indicated that hsa_circ_0009109 was significantly down-expressed in GC tissues and cell lines.A reduction in cytoplasmic-derived hsa_circ_0009109 could promote GC progression by accelerating cell proliferation,enhancing migration and invasion,inhibiting apoptosis,and accelerating the cell cycle progression.Besides,hsa_circ_0009109 was found to exert the effect of an autophagy inhibitor such as 3-Methyladenine(3-MA),which was manifested by the weakening of the immunofluorescence of LC3B and the reduction in autophagy-related proteins after overexpression of hsa_circ_0009109,while increased autophagosomes were observed after interference with hsa_circ_0009109.Subsequently,the crosstalk between hsa_circ_0009109 and miR-544a-3p/bcl-2 was verified using dual-luciferase reporter assay.The autophagy status was altered under the regulation of the hsa_circ_0009109-targeted miR-544a-3p/bcl-2 axis.Conclusions:The hsa_circ_0009109 mediated a novel autophagy regulatory network through targeting the miR-544a-3p/bcl-2 axis,which may shed new light on the exploration of therapeutic targets for the clinical treatment of GC.展开更多
The numerical integration of phase-field equations is a delicate task which needs to recover at the discrete level intrinsic properties of the solution such as energy dissipation and maximum principle.Although the the...The numerical integration of phase-field equations is a delicate task which needs to recover at the discrete level intrinsic properties of the solution such as energy dissipation and maximum principle.Although the theory of energy dissipation for classical phase field models is well established,the corresponding theory for time-fractional phase-field models is still incomplete.In this article,we study certain nonlocal-in-time energies using the first-order stabilized semi-implicit L1 scheme.In particular,we will establish a discrete fractional energy law and a discrete weighted energy law.The extension for a(2-α)-order L1 scalar auxiliary variable scheme will be investigated.Moreover,we demonstrate that the energy bound is preserved for the L1 schemes with nonuniform time steps.Several numerical experiments are carried to verify our theoretical analysis.展开更多
Enhancer of Zeste homolog 2(EzH2),a histone methyltransferase within polycomb repressive complex 2(PRC2),plays a crucial role in epigenetic regulation by silencing gene expression through trimethylation of histone 3 a...Enhancer of Zeste homolog 2(EzH2),a histone methyltransferase within polycomb repressive complex 2(PRC2),plays a crucial role in epigenetic regulation by silencing gene expression through trimethylation of histone 3 at lysine 27(H3K27me3).Beyond its well-documented oncogenic functions,emerging research has revealed EZH2's involvement in various non-cancerous pathologies.For instance,EZH2 is critical in regulating immune responses,particularly in modulating T cell differentiation and cytokine production,which affects inflammation and immune homeostasis.EzH2 also controls fibroblast activation and extracellular matrix(ECM)remodeling,influencing critical processes such as cell differentiation,tissue repair and energy homeostasis.Additionally,EzH2's epigenetic regulation of neuroinflammatory processes is linked to neuronal health and survival.Recent advancements in EZH2 inhibitor therapies demonstrate promising potential for treating a range of non-cancerous conditions,with preclinical trials suggesting efficacy in mitigating disease progression.This review highlights the expanding functional scope of EZH2,emphasizing its epigenetic mechanisms and the therapeutic opportunities for targeting EZH2 in non-cancerous diseases.展开更多
Lipid droplets, which are conserved across almost all species, are cytoplasmic organelles used to store neutral lipids. Identification of lipid droplet regulators will be conducive to resolving obesity and other fat-a...Lipid droplets, which are conserved across almost all species, are cytoplasmic organelles used to store neutral lipids. Identification of lipid droplet regulators will be conducive to resolving obesity and other fat-associated diseases. In this paper, we selected 11 candidates that might be associated with lipid metabolism in Caenorhabditis elegans . Using a BODIPY 493/503-based flow cytometry screen, 6 negative and 3 positive regulators of fat content were identified. We selected one negative regulator of lipid content, C13C4.5 , for future study. C13C4.5 was mainly expressed in the worm intestine. We found that this gene was important for maintaining the metabolism of lipid droplets. Biochemical results revealed that 50% of triacylglycerol (TAG) was lost in C13C4.5 knockout worms. Stimulated Raman scattering (SRS) signals in C13C4.5 mutants showed only 49.6% of the fat content in the proximal intestinal region and 86.3% in the distal intestinal region compared with wild type animals. The mean values of lipid droplet size and intensity in C13C4.5 knockout animals were found to be significantly decreased compared with those in wild type worms. The LMP-1-labeled membrane structures in worm intestines were also enlarged in C13C4.5 mutant animals. Finally, fertility defects were found in C13C4.5 ( ok2087 ) mutants. Taken together, these results indicate that C13C4.5 may regulate the fertility of C. elegans by changing the size and fat content of lipid droplets by interfering with lysosomal morphology and function.展开更多
By comprehensive utilizing of the geometry structure of 2D Burgers equation and the stochastic noise,we find the decay properties of the solution to the stochastic 2D Burgers equation with Dirichlet boundary condition...By comprehensive utilizing of the geometry structure of 2D Burgers equation and the stochastic noise,we find the decay properties of the solution to the stochastic 2D Burgers equation with Dirichlet boundary conditions.Consequently,the expected ergodicity for this turbulence model is established.展开更多
In this paper,we propose and analyze high order energy dissipative time-stepping schemes for time-fractional molecular beam epitaxial(MBE)growth model on the nonuniform mesh.More precisely,(2−α)-order,secondorder and...In this paper,we propose and analyze high order energy dissipative time-stepping schemes for time-fractional molecular beam epitaxial(MBE)growth model on the nonuniform mesh.More precisely,(2−α)-order,secondorder and(3−α)-order time-stepping schemes are developed for the timefractional MBE model based on the well known L1,L2-1σ,and L2 formulations in discretization of the time-fractional derivative,which are all proved to be unconditional energy dissipation in the sense of a modified discrete nonlocalenergy on the nonuniform mesh.In order to reduce the computational storage,we apply the sum of exponential technique to approximate the history part of the time-fractional derivative.Moreover,the scalar auxiliary variable(SAV)approach is introduced to deal with the nonlinear potential function and the history part of the fractional derivative.Furthermore,only first order method is used to discretize the introduced SAV equation,which will not affect high order accuracy of the unknown thin film height function by using some proper auxiliary variable functions V(ξ).To our knowledge,it is the first time to unconditionally establish the discrete nonlocal-energy dissipation law for the modified L1-,L2-1σ-,and L2-based high-order schemes on the nonuniform mesh,which is essentially important for such time-fractional MBE models with low regular solutions at initial time.Finally,a series of numerical experiments are carried out to verify the accuracy and efficiency of the proposed schemes.展开更多
基金supported by the Guangdong Provincial Key Laboratory IRADS(2022B1212010006,R0400001-22)。
文摘Obesity has become a significant global public health issue.Previous studies have found that the Chenpi has the anti-obesity activity.However,the anti-obesity phytochemicals and their mechanisms are still unclear.This study investigated the anti-obesity phytochemicals and molecular mechanisms involved in treating obesity by Chenpi through network pharmacology and molecular docking.A total of 17 bioactive phytochemicals from Chenpi and its 475 related anti-obesity targets have been identified.The KEGG pathway analysis showed that the PI3K/Akt signaling pathway,MAPK signaling pathway,AMPK signaling pathway,and nuclear factor kappa B signaling pathway are the main signaling pathways involved in the anti-obesity effect of Chenpi.According to molecular docking analysis,the phytochemicals of Chenpi can bind to central anti-obesity targets.Based on the ADMET analysis and network pharmacology results,tangeretin exhibited the lowest predicted toxicity and potential for anti-obesity effects.In the in vitro lipid accumulation model,tangeretin effectively suppressed the free fatty acid-induced lipid in Hep G2 cells by upregulating the PI3K/Akt/GSK3βsignaling pathway based on the result of q-PCR and Western blotting.The outcomes of this research give insights for future research on the anti-obesity phytochemicals and molecular mechanisms derived from Chenpi,also providing the theoretical basis for developing anti-obesity functional foods based on Chenpi.
基金supported by grants from the Foundation for Distinguished Young Talents in Higher Education of Guangdong,China(2024KQNCX157)Our work was also supported in part by the Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science,BNU-HKBU United International College(2022B1212010006)+1 种基金in part by the Guangdong Higher Education Upgrading Plan(2021-2025)of“Rushing to the Top,Making Up Shortcomings and Strengthening Special Features”(R0400001-22)Additionally,we acknowledge support from the Zhuhai Basic and Applied Basic ResearchFoundation(2220004002717).
文摘CRISPR-Cas technology has revolutionized our ability to understand and engineer organisms,evolving from a singular Cas9 model to a diverse CRISPR toolbox.A critical bottleneck in developing new Cas proteins is identifying protospacer adjacent motif(PAM)sequences.Due to the limitations of experimental methods,bioinformatics approaches have become essential.However,existing PAM prediction programs are limited by the small number of spacers in CRISPR-Cas systems,resulting in low accuracy.To address this,we develop PAMPHLET,a pipeline that uses homology searches to identify additional spacers,significantly increasing the number of spacers up to 18-fold.PAMPHLET is validated on 20 CRISPR-Cas systems and successfully predicts PAM sequences for 18 protospacers.These predictions are further validated using the DocMF platform,which characterizes protein-DNA recognition patterns via next-generation sequencing.The high consistency between PAMPHLET predictions and DocMF results for Cas proteins demonstrates the potential of PAMPHLET to enhance PAM sequence prediction accuracy,expedite the discovery process,and accelerate the development of CRISPR tools.
基金This work was supported in part by the JSPS(Japan Society for the Promotion of Science)KAKENHI(20H04566,22H03998)the National Natural Science Foundation of China(61873348)+1 种基金the Natural Science Foundation of Hubei Province,China(2020CFA031)Wuhan Applied Foundational Frontier Project(2020010601012175).
文摘Active disturbance-rejection methods are effective in estimating and rejecting disturbances in both transient and steady-state responses.This paper presents a deep observation on and a comparison between two of those methods:the generalized extended-state observer(GESO)and the equivalent input disturbance(EID)from assumptions,system configurations,stability conditions,system design,disturbance-rejection performance,and extensibility.A time-domain index is introduced to assess the disturbance-rejection performance.A detailed observation of disturbance-suppression mechanisms reveals the superiority of the EID approach over the GESO method.A comparison between these two methods shows that assumptions on disturbances are more practical and the adjustment of disturbance-rejection performance is easier for the EID approach than for the GESO method.
基金supported by the UIC Research Grants with No.of(R201912 and R202010)the Curriculum Development and Teaching Enhancement with No.of(UICR0400046-21CTL)+1 种基金the Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science,BNU-HKBU United International College with No.of(2022B1212010006)Guangdong Higher Education Upgrading Plan(2021-2025)with No.of(UICR0400001-22).
文摘A uniform experimental design(UED)is an extremely used powerful and efficient methodology for designing experiments with high-dimensional inputs,limited resources and unknown underlying models.A UED enjoys the following two significant advantages:(i)It is a robust design,since it does not require to specify a model before experimenters conduct their experiments;and(ii)it provides uniformly scatter design points in the experimental domain,thus it gives a good representation of this domain with fewer experimental trials(runs).Many real-life experiments involve hundreds or thousands of active factors and thus large UEDs are needed.Constructing large UEDs using the existing techniques is an NP-hard problem,an extremely time-consuming heuristic search process and a satisfactory result is not guaranteed.This paper presents a new effective and easy technique,adjusted Gray map technique(AGMT),for constructing(nearly)UEDs with large numbers of four-level factors and runs by converting designs with s two-level factors and n runs to(nearly)UEDs with 2^(t−1)s four-level factors and 2tn runs for any t≥0 using two simple transformation functions.Theoretical justifications for the uniformity of the resulting four-level designs are given,which provide some necessary and/or sufficient conditions for obtaining(nearly)uniform four-level designs.The results show that the AGMT is much easier and better than the existing widely used techniques and it can be effectively used to simply generate new recommended large(nearly)UEDs with four-level factors.
基金Supported by Training Program of the National Natural Science Foundation of China,No.2021-ZLLH-05National Cancer Center Climbing Fund,No.NCC201906B02+1 种基金Shenyang Municipal Science and Technology Public Health Research and Development Special Project,No.21-172-9-03 and No.22-321-33-53Dalian University of Technology-Liaoning Cancer Hospital Medical Engineering Cross-Union Fund,No.LD202309。
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide.Glycolysis has been demonstrated to be pivotal for the carcinogenesis of GC.AIM To develop a glycolysis-based gene signature for prognostic evaluation in GC patients.METHODS Differentially expressed genes correlated with glycolysis were identified in stomach adenocarcinoma data(STAD).A risk score was established through a univariate Cox and least absolute shrinkage and selection operator analysis.The model was evaluated using the area under the receiver operating characteristic curves.RNA-sequencing data from high-and low-glycolysis groups of STAD patients were analyzed using Cibersort algorithm and Spearman correlation to analyze the interaction of immune cell infiltration and glycolysis.Multiomics characteristics in different glycolysis status were also analyzed.RESULTS A five-gene signature comprising syndecan 2,versican,malic enzyme 1,pyruvate carboxylase and SRY-box transcription factor 9 was constructed.Patients were separated to high-or low-glycolysis groups according to risk scores.Overall survival of patients with high glycolysis was poorer.The sensitivity and specificity of the model in prediction of survival of GC patients were also observed by receiver operating characteristic curves.A nomogram including clinicopathological characteristics and the risk score also showed good prediction for 3-and 5-year overall survival.Gene set variation analysis showed that high-glycolysis patients were related to dysregulation of pancreas beta cells and estrogen late pathways,and low-glycolysis patients were related to Myc targets,oxidative phosphorylation,mechanistic target of rapamycin complex 1 signaling and G2M checkpoint pathways.Tumor-infiltrating immune cells and multiomics analysis suggested that the different glycolysis status was significantly correlated with multiple immune cell infiltration.The patients with high glycolysis had lower tumor mutational burden and neoantigen load,higher incidence of microsatellite instability and lower chemosensitivity.High glycolysis status was often found among patients with grade 2/3 cancer or poor prognosis.CONCLUSION The genetic characteristics revealed by glycolysis could predict the prognosis of GC.High glycolysis significantly affects GC phenotype,but the detailed mechanism needs to be further studied.
基金supported by grants from the Cultivation Program of National Science Foundation of Liaoning Cancer Hospital (China) (No.2021-ZLLH-03)Beijing Xisike Clinical Oncology Research Foundation (China) (No.Y-QL202101-0039)+2 种基金Medical and Industrial Cross Joint Fund of Dalian University of Technology-Liaoning Cancer Hospital (China) (No.LD2023027)The National Natural Science Foundation of China (No.82303131)the Liaoning Province Science and Technology Plan Joint Program (Applied Basic Research Project) (China) (No.2023JH2/101700150).
文摘For prognosis and therapeutic response,colorectal cancer(CRC)patients are highly variable across stages,correlated to high inter-tumor heterogeneity at the molecular level.1 Therefore,molecular subtyping needs to be determined for stratifying patients into distinct prognostic subgroups according to tumor biology.
基金supported by National Natural Science Foundation of China(Grant No.12271047)Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science,Beijing Normal-Hong Kong Baptist University(Grant No.2022B1212010006)+1 种基金United International College Research Grant(Grant Nos.R0400001-22,UICR0400008-21 and UICR04202405-21)Guangdong College Enhancement and Innovation Program(Grant No.2021ZDZX1046).
文摘Wu functions are a class of positive definite compactly supported radial basis functions in terms of piecewise polynomials.They are similar to Wendland functions that came up shortly later and they still require further investigation.Here,we prove that the native space of a Wu function is a dense subspace of a Sobolev space and give an explicit characterization of the native spaces of Wu functions.In addition,three definitions of Wu functions are introduced and proven to be equivalent.Based on these new equivalent definitions and the so-called f-form,we can generalize the Wu functions for the even-dimensional spaces,while the original Wu functions are proven to have odd maximal possible dimensions on which they are positive definite.Such functions in even-dimensional spaces will be called the“missing Wu functions”.Furthermore,we can generalize the Wu functions to“fractional”-dimensional spaces.We call all these Wu functions the generalized Wu functions.The closed form of the generalized Wu functions is given in terms of hypergeometric functions.Finally,we prove that the Wu functions and the missing Wu functions can be written as linear combinations of the generalized Wendland functions.
基金partially supported by the National Natural Science Foundation of China/Hong Kong RGC Joint Research Scheme(NSFC/RGC 11961160718)the fund of the Guangdong Provincial Key Laboratory of Computational Science And Material Design(No.2019B030301001)+4 种基金supported in part by the Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science under UIC 2022B1212010006supported by the National Science Foundation of China(NSFC)Grant No.12271240supported by NSFC Grant 12271241Guangdong Basic and Applied Basic Research Foundation(No.2023B1515020030)Shenzhen Science and Technology Program(Grant No.RCYX20210609104358076).
文摘In this article,we study the energy dissipation property of time-fractional Allen–Cahn equation.On the continuous level,we propose an upper bound of energy that decreases with respect to time and coincides with the original energy at t=0 and as t tends to∞.This upper bound can also be viewed as a nonlocal-in-time modified energy which is the summation of the original energy and an accumulation term due to the memory effect of time-fractional derivative.In particular,the decrease of the modified energy indicates that the original energy indeed decays w.r.t.time in a small neighborhood at t=0.We illustrate the theory mainly with the time-fractional Allen-Cahn equation but it could also be applied to other time-fractional phase-field models such as the Cahn-Hilliard equation.On the discrete level,the decreasing upper bound of energy is useful for proving energy dissipation of numerical schemes.First-order L1 and second-order L2 schemes for the time-fractional Allen-Cahn equation have similar decreasing modified energies,so that stability can be established.Some numerical results are provided to illustrate the behavior of this modified energy and to verify our theoretical results.
基金supported by the National Natural Science Foundation of China[nos 82272411,82072363]Jiangsu Innovative and Entrepreneurial Talent Programme[JSSCBS20211602]+3 种基金PhD Research Startup Foundation of Affiliated Hospital of Nantong University[Tdb2011]Postdoctoral Research Foundation of Affiliated Hospital of Nantong University[BSH202110]Scientific Research Project of Nantong Municipal Health Commission[QN2022015],Nantong Basic Research Program[JC12022007]Grants from Jiangsu Provincial Research Hospital[YJXYY202204-YSC28].
文摘Background:Autophagy death of cancer cells is detrimental to apoptosis induced by therapeutic drugs,which promotes tumor progression to a certain extent.Increasing reports have demonstrated the regulatory role of circular RNAs(circRNAs)in autophagy.Here,we aimed to determine the role of hsa_circ_0009109 in autophagy in gastric cancer(GC).Methods:The effects of hsa_circ_0009109 on autophagy were examined using quantitative real-time polymerase chain reaction(qPCR),transmission electron microscopy,Western blot,and immunofluorescence.The mechanism of hsa_circ_0009109 regulating the miR-544a-3p/bcl-2 axis was analysed using fluorescence in situ hybridization,dual-luciferase reporter,and rescue experiments.Results:Functional testing indicated that hsa_circ_0009109 was significantly down-expressed in GC tissues and cell lines.A reduction in cytoplasmic-derived hsa_circ_0009109 could promote GC progression by accelerating cell proliferation,enhancing migration and invasion,inhibiting apoptosis,and accelerating the cell cycle progression.Besides,hsa_circ_0009109 was found to exert the effect of an autophagy inhibitor such as 3-Methyladenine(3-MA),which was manifested by the weakening of the immunofluorescence of LC3B and the reduction in autophagy-related proteins after overexpression of hsa_circ_0009109,while increased autophagosomes were observed after interference with hsa_circ_0009109.Subsequently,the crosstalk between hsa_circ_0009109 and miR-544a-3p/bcl-2 was verified using dual-luciferase reporter assay.The autophagy status was altered under the regulation of the hsa_circ_0009109-targeted miR-544a-3p/bcl-2 axis.Conclusions:The hsa_circ_0009109 mediated a novel autophagy regulatory network through targeting the miR-544a-3p/bcl-2 axis,which may shed new light on the exploration of therapeutic targets for the clinical treatment of GC.
基金supported by the NSFC/Hong Kong RGC Joint Research Scheme(Grant No.NSFC/RGC 11961160718)supported by the National Natural Science Foundation of China(NSFC)(Grant No.12271240)+4 种基金by the fund of the Guangdong Provincial Key Laboratory of Computational Science and Material Design,China(Grant No.2019B030301001)by the Shenzhen Natural Science Fund(Grant No.RCJC20210609103819018)supported by the NSFC(Grant No.12271241)by the Guangdong Basic and Applied Basic Research Foundation(Grant No.2023B1515020030)by the Shenzhen Science and Technology Program(Grant Nos.RCYX2021060,9104358076).
文摘The numerical integration of phase-field equations is a delicate task which needs to recover at the discrete level intrinsic properties of the solution such as energy dissipation and maximum principle.Although the theory of energy dissipation for classical phase field models is well established,the corresponding theory for time-fractional phase-field models is still incomplete.In this article,we study certain nonlocal-in-time energies using the first-order stabilized semi-implicit L1 scheme.In particular,we will establish a discrete fractional energy law and a discrete weighted energy law.The extension for a(2-α)-order L1 scalar auxiliary variable scheme will be investigated.Moreover,we demonstrate that the energy bound is preserved for the L1 schemes with nonuniform time steps.Several numerical experiments are carried to verify our theoretical analysis.
基金supported by grant 2022YFA1104001 from the National Key Research and Development Program of ChinaGrants Nos.82272745,81972966,82203433,82404099 and 82404113 from the National Natural Science Foundation of China+2 种基金grants BYSYZD2023010(to LXX),BYSY2022070(to YQW),BYSYZD2023041(to JLZ)and BYSYRCYJ2023004(to JLZ)from Peking University Third Hospital Clinical Key Projectgrant 2023A1515111068 from Basic and Applied Basic Research Foundation of Guangdong Provincegrant JCYJ20230807095121041 from Shenzhen Science and Technology Program.
文摘Enhancer of Zeste homolog 2(EzH2),a histone methyltransferase within polycomb repressive complex 2(PRC2),plays a crucial role in epigenetic regulation by silencing gene expression through trimethylation of histone 3 at lysine 27(H3K27me3).Beyond its well-documented oncogenic functions,emerging research has revealed EZH2's involvement in various non-cancerous pathologies.For instance,EZH2 is critical in regulating immune responses,particularly in modulating T cell differentiation and cytokine production,which affects inflammation and immune homeostasis.EzH2 also controls fibroblast activation and extracellular matrix(ECM)remodeling,influencing critical processes such as cell differentiation,tissue repair and energy homeostasis.Additionally,EzH2's epigenetic regulation of neuroinflammatory processes is linked to neuronal health and survival.Recent advancements in EZH2 inhibitor therapies demonstrate promising potential for treating a range of non-cancerous conditions,with preclinical trials suggesting efficacy in mitigating disease progression.This review highlights the expanding functional scope of EZH2,emphasizing its epigenetic mechanisms and the therapeutic opportunities for targeting EZH2 in non-cancerous diseases.
基金support from the National Basic Research Program(973 Program)(Nos.2013CB910103 and 2010CB912303)the National Natural Science Foundation of China(Grant Nos.31170818 and 31270910)the project from the Chinese Academy of Sciences(KSCX2-EW-Q-11).
文摘Lipid droplets, which are conserved across almost all species, are cytoplasmic organelles used to store neutral lipids. Identification of lipid droplet regulators will be conducive to resolving obesity and other fat-associated diseases. In this paper, we selected 11 candidates that might be associated with lipid metabolism in Caenorhabditis elegans . Using a BODIPY 493/503-based flow cytometry screen, 6 negative and 3 positive regulators of fat content were identified. We selected one negative regulator of lipid content, C13C4.5 , for future study. C13C4.5 was mainly expressed in the worm intestine. We found that this gene was important for maintaining the metabolism of lipid droplets. Biochemical results revealed that 50% of triacylglycerol (TAG) was lost in C13C4.5 knockout worms. Stimulated Raman scattering (SRS) signals in C13C4.5 mutants showed only 49.6% of the fat content in the proximal intestinal region and 86.3% in the distal intestinal region compared with wild type animals. The mean values of lipid droplet size and intensity in C13C4.5 knockout animals were found to be significantly decreased compared with those in wild type worms. The LMP-1-labeled membrane structures in worm intestines were also enlarged in C13C4.5 mutant animals. Finally, fertility defects were found in C13C4.5 ( ok2087 ) mutants. Taken together, these results indicate that C13C4.5 may regulate the fertility of C. elegans by changing the size and fat content of lipid droplets by interfering with lysosomal morphology and function.
基金Supported by National Key R and D Program of China(Grant No.2020YFA0712700)NSFC(Grant Nos.11931004,11971077,12090014)+3 种基金Key Laboratory of Random Complex Structures and Data Science,Academy of Mathematics and Systems Science,Chinese Academy of Sciences(Grant No.2008DP173182)Chongqing Key Laboratory of Analytic Mathematics and Applications,Chongqing University,Natural Science Foundation Project of CQ(Grant No.cstc2020jcyjmsxmX0441)Fundamental Research Funds for the Central Universities(Grant No.2020CDJ-LHZZ-027)UIC Start-up Research Fund(Grant No.UICR0700072-24)。
文摘By comprehensive utilizing of the geometry structure of 2D Burgers equation and the stochastic noise,we find the decay properties of the solution to the stochastic 2D Burgers equation with Dirichlet boundary conditions.Consequently,the expected ergodicity for this turbulence model is established.
基金supported by NSFC grant 12001248,the NSF of Jiangsu Province grant BK20201020the NSF of Universities in Jiangsu Province of China grant 20KJB110013+3 种基金the Hong Kong Polytechnic University grant 1-W00Dsupported by Hong Kong Research Grants Council RFS grant RFS2021-5S03 and GRF grant 15302122,the Hong Kong Polytechnic University grant 1-9BCTCAS AMSS-PolyU Joint Laboratory of Applied Mathematicssupported by the Guangdong Provincial Key Laboratory of Interdisciplinary Research and Application for Data Science under UIC 2022B1212010006.
文摘In this paper,we propose and analyze high order energy dissipative time-stepping schemes for time-fractional molecular beam epitaxial(MBE)growth model on the nonuniform mesh.More precisely,(2−α)-order,secondorder and(3−α)-order time-stepping schemes are developed for the timefractional MBE model based on the well known L1,L2-1σ,and L2 formulations in discretization of the time-fractional derivative,which are all proved to be unconditional energy dissipation in the sense of a modified discrete nonlocalenergy on the nonuniform mesh.In order to reduce the computational storage,we apply the sum of exponential technique to approximate the history part of the time-fractional derivative.Moreover,the scalar auxiliary variable(SAV)approach is introduced to deal with the nonlinear potential function and the history part of the fractional derivative.Furthermore,only first order method is used to discretize the introduced SAV equation,which will not affect high order accuracy of the unknown thin film height function by using some proper auxiliary variable functions V(ξ).To our knowledge,it is the first time to unconditionally establish the discrete nonlocal-energy dissipation law for the modified L1-,L2-1σ-,and L2-based high-order schemes on the nonuniform mesh,which is essentially important for such time-fractional MBE models with low regular solutions at initial time.Finally,a series of numerical experiments are carried out to verify the accuracy and efficiency of the proposed schemes.
