BACKGROUND The prevalence of colorectal cancer(CRC)in younger people is increasing.Despite advances in precision medicine,the challenges of drug resistance and high costs persist.Nitidine chloride(NC)has pharmacologic...BACKGROUND The prevalence of colorectal cancer(CRC)in younger people is increasing.Despite advances in precision medicine,the challenges of drug resistance and high costs persist.Nitidine chloride(NC)has pharmacological potential,and kinesin family member 20A(KIF20A)is overexpressed in various tumors;however,their interaction in CRC remains unexplored.AIM To investigate the KIF20A expression characteristics in CRC cells and determine whether it is a potential target gene for NC in inhibiting CRC treatment.METHODS Single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and mRNA expression profiling were used to analyze KIF20A expression in CRC cells.Immunohistochemical staining was used to verify KIF20A expression in 416 clinical samples(208 CRC tissue samples and 208 noncancerous control tissue samples).Clustered regularly interspaced short palindromic repeats(CRISPR)technology was used to evaluate the impact of knocking out KIF20A on CRC cell growth.Molecular docking was applied to analyze NC–KIF20A binding.Finally,RNA sequencing and functional enrichment analysis were performed to explore the mechanism of action of NC in CRC cells.RESULTS Treating HCT116 cells with NC was found to significantly downregulate KIF20A(P<0.05),and the molecular docking analysis revealed high-affinity binding between NC and KIF20A(binding energy=-9.6 kcal/mol).The scRNA-seq,spatial transcriptomics,and mRNA expression profiling results confirmed the significantly high expression of KIF20A in CRC tissues(standardized mean difference=1.33,95%confidence interval:0.885-1.77,summary receiver operating characteristic curve area=0.94).The immunohistochemical analysis of the clinical samples showed high KIF20A expression in the CRC tissues(P<0.05),with significant correlation between the level of expression and gender,tumor size,and tumor grade(P<0.05).Knocking out KIF20A significantly inhibited the growth of various CRC cell lines(CRISPR score<-0.3).The functional enrichment analysis indicated that NC may inhibit CRC by disrupting several biological processes,such as mitotic nuclear division,chromosome segregation,and microtubule binding.CONCLUSION Our results indicate that NC binds to KIF20A with high affinity and downregulates its expression in CRC cells,leading to reduced proliferation.Hence,NC has promise as a therapeutic agent in the treatment of CRC,and targeting KIF20A also has potential as a therapeutic strategy.Further KIF20A knockout studies are needed to confirm the binding specificity and mechanistic roles of NC in CRC.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2...BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2F transcription factor 1(E2F1)-mediated transcriptional activation.This study integrates multiomics and clustered regularly interspaced short palindromic repeats(CRISPR)screening to delineate RAC3’s roles.RAC3 overexpression correlates with advanced HCC and patient age,while its knockout suppresses proliferation.Mechanistically,RAC3 dysregulates cell-cycle checkpoints through E2F1 binding.Pharmacological RAC3 inhibition disrupts tumor growth and synergizes with chemotherapy to overcome resistance.AIM To explore RAC3’s expression,clinical links,and HCC mechanisms via multiomics and functional genomics.METHODS Multiomic integration of The Cancer Genome Atlas(TCGA),Gene Expression Omnibus,and Genotype-Tissue Expression datasets was performed to analyze RAC3 mRNA expression.Immunohistochemistry quantified RAC3 protein in 108 HCC/adjacent tissue pairs.Kaplan–Meier/Cox regression assessed prognostic significance using TCGA data.CRISPR screening validated RAC3’s necessity for HCC proliferation.Functional enrichment identified associated pathways;hTFtarget/JASPAR predicted transcription factors,validated via chromatin immunoprecipitation sequencing(ChIP-seq).RESULTS RAC3 exhibited significant mRNA and protein overexpression in HCC tissues,which was correlated with advanced tumor stages and reduced overall survival rates(hazard ratio=1.82,95%CI:1.31–2.53).Genetic ablation of RAC3 suppressed HCC cell proliferation across 16 cell lines.Pathway analysis revealed RAC3’s predominant involvement in cell-cycle regulation,DNA replication,and nucleocytoplasmic transport.Mechanistic investigations identified E2F1 as a pivotal upstream transcriptional regulator,and ChIP-seq analysis validated its direct binding to the RAC3 promoter region.These findings suggest that RAC3 drives HCC progression through E2F1-mediated cell-cycle dysregulation.CONCLUSION This study identified RAC3 as a key HCC oncogenic driver;its overexpression links to poor prognosis/resistance.Targeting the RAC3/E2F1 axis offers a new therapy,which highlights RAC3 as a biomarker/target.展开更多
This paper is concerned with the convergence rates of ergodic limits and approximation for regularized resolvent families for a linear Volterra integral equation. The results contain C 0-semigroups, cosine operator fu...This paper is concerned with the convergence rates of ergodic limits and approximation for regularized resolvent families for a linear Volterra integral equation. The results contain C 0-semigroups, cosine operator functions and α-times integrated resolvent family as special cases.展开更多
Let and A be the generator of an -times resolvent family on a Banach space X. It is shown that the fractional Cauchy problem has maximal regularity on if and only if is of bounded semivariation on .
This paper aims to verify the family support situation for primary school children with intellectual disabilities learning in regular class and to explore various educational strategies to promote their development.A ...This paper aims to verify the family support situation for primary school children with intellectual disabilities learning in regular class and to explore various educational strategies to promote their development.A self-made questionnaire was used in this survey,and the parents of 380 intellectual disabled students were the subjects of this survey.It turns out that the overall family support for intellectual disabled children learning in regular class in China is good,but it is affected by the degree of obstacles.Factors such as grade,gender,and parental education had no significant effect on family support.It is the shared responsibility of the government,schools,and parents to promote the level of family support.Governments at all levels must implement family support projects,schools must carry out family education guidance to impart scientific parenting knowledge,and parents must take note of their own responsibilities,so as to promote the physical and mental development of children with intellectual disabilities.展开更多
This article is concerned with the ill-posed Cauchy problem associated with a densely defined linear operator A in a Banach space. A family of weak regularizing operators is introduced. If the spectrum of A is contain...This article is concerned with the ill-posed Cauchy problem associated with a densely defined linear operator A in a Banach space. A family of weak regularizing operators is introduced. If the spectrum of A is contained in a sector of right-half complex plane and its resolvent is polynomially bounded, the weak regularization for such ill-posed Cauchy problem can be shown by using the quasi-reversibilky method and regularized semigroups. Finally, an example is given.展开更多
In this paper, α-times integrated C-regularized cosine functions and mild α-times integrated C-existence families of second order are introduced. Equivalences are proved among α-times integrated C-regularized cosin...In this paper, α-times integrated C-regularized cosine functions and mild α-times integrated C-existence families of second order are introduced. Equivalences are proved among α-times integrated C-regularized cosine function for a linear operator A, C-wellposed of (α+1)-times abstract Cauchy problem and mild a -times integrated C-existence family of second order for A when the commutable condition is satisfied. In addition, if A = C-1AC, they are also equivalent to A generating the α -times integrated C-regularized cosine function. The characterization of an exponentially bounded mild α -times integrated C-existence family of second order is given out in terms of a Laplace transform.展开更多
In this paper, we study the regularity of mild solution for the following fractional abstract Cauchy problem Dt αu(t)=Au(t)+f(t), t ∈ (0,T] u(0)= x0 on a Banach space X with order α ∈ (0,1), where the fractional d...In this paper, we study the regularity of mild solution for the following fractional abstract Cauchy problem Dt αu(t)=Au(t)+f(t), t ∈ (0,T] u(0)= x0 on a Banach space X with order α ∈ (0,1), where the fractional derivative is understood in the sense of Caputo fractional derivatives. We show that if A generates an analytic α-times resolvent family on X and f ∈ Lp ([0,T];X) for some p > 1/α, then the mild solution to the above equation is in Cα-1/p[ò,T] for every ò > 0. Moreover, if f is H?lder continuous, then so are the Dt αu(t) and Au(t).展开更多
基金Supported by the Promoting Project of Basic Capacity for Young and Middle-aged University Teachers in Guangxi,No.2025KY0164Youth Science Foundation of Guangxi Medical University,No.GXMUYSF202423Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220415 and No.Z20210442.
文摘BACKGROUND The prevalence of colorectal cancer(CRC)in younger people is increasing.Despite advances in precision medicine,the challenges of drug resistance and high costs persist.Nitidine chloride(NC)has pharmacological potential,and kinesin family member 20A(KIF20A)is overexpressed in various tumors;however,their interaction in CRC remains unexplored.AIM To investigate the KIF20A expression characteristics in CRC cells and determine whether it is a potential target gene for NC in inhibiting CRC treatment.METHODS Single-cell RNA sequencing(scRNA-seq),spatial transcriptomics,and mRNA expression profiling were used to analyze KIF20A expression in CRC cells.Immunohistochemical staining was used to verify KIF20A expression in 416 clinical samples(208 CRC tissue samples and 208 noncancerous control tissue samples).Clustered regularly interspaced short palindromic repeats(CRISPR)technology was used to evaluate the impact of knocking out KIF20A on CRC cell growth.Molecular docking was applied to analyze NC–KIF20A binding.Finally,RNA sequencing and functional enrichment analysis were performed to explore the mechanism of action of NC in CRC cells.RESULTS Treating HCT116 cells with NC was found to significantly downregulate KIF20A(P<0.05),and the molecular docking analysis revealed high-affinity binding between NC and KIF20A(binding energy=-9.6 kcal/mol).The scRNA-seq,spatial transcriptomics,and mRNA expression profiling results confirmed the significantly high expression of KIF20A in CRC tissues(standardized mean difference=1.33,95%confidence interval:0.885-1.77,summary receiver operating characteristic curve area=0.94).The immunohistochemical analysis of the clinical samples showed high KIF20A expression in the CRC tissues(P<0.05),with significant correlation between the level of expression and gender,tumor size,and tumor grade(P<0.05).Knocking out KIF20A significantly inhibited the growth of various CRC cell lines(CRISPR score<-0.3).The functional enrichment analysis indicated that NC may inhibit CRC by disrupting several biological processes,such as mitotic nuclear division,chromosome segregation,and microtubule binding.CONCLUSION Our results indicate that NC binds to KIF20A with high affinity and downregulates its expression in CRC cells,leading to reduced proliferation.Hence,NC has promise as a therapeutic agent in the treatment of CRC,and targeting KIF20A also has potential as a therapeutic strategy.Further KIF20A knockout studies are needed to confirm the binding specificity and mechanistic roles of NC in CRC.
基金Supported by National Natural Science Foundation of China,No.82260581.
文摘BACKGROUND Hepatocellular carcinoma(HCC)remains a lethal malignancy due to its molecular complexity and chemoresistance.Rac family small GTPase 3(RAC3),a tumorigenic GTPase understudied in HCC,drives recurrence via E2F transcription factor 1(E2F1)-mediated transcriptional activation.This study integrates multiomics and clustered regularly interspaced short palindromic repeats(CRISPR)screening to delineate RAC3’s roles.RAC3 overexpression correlates with advanced HCC and patient age,while its knockout suppresses proliferation.Mechanistically,RAC3 dysregulates cell-cycle checkpoints through E2F1 binding.Pharmacological RAC3 inhibition disrupts tumor growth and synergizes with chemotherapy to overcome resistance.AIM To explore RAC3’s expression,clinical links,and HCC mechanisms via multiomics and functional genomics.METHODS Multiomic integration of The Cancer Genome Atlas(TCGA),Gene Expression Omnibus,and Genotype-Tissue Expression datasets was performed to analyze RAC3 mRNA expression.Immunohistochemistry quantified RAC3 protein in 108 HCC/adjacent tissue pairs.Kaplan–Meier/Cox regression assessed prognostic significance using TCGA data.CRISPR screening validated RAC3’s necessity for HCC proliferation.Functional enrichment identified associated pathways;hTFtarget/JASPAR predicted transcription factors,validated via chromatin immunoprecipitation sequencing(ChIP-seq).RESULTS RAC3 exhibited significant mRNA and protein overexpression in HCC tissues,which was correlated with advanced tumor stages and reduced overall survival rates(hazard ratio=1.82,95%CI:1.31–2.53).Genetic ablation of RAC3 suppressed HCC cell proliferation across 16 cell lines.Pathway analysis revealed RAC3’s predominant involvement in cell-cycle regulation,DNA replication,and nucleocytoplasmic transport.Mechanistic investigations identified E2F1 as a pivotal upstream transcriptional regulator,and ChIP-seq analysis validated its direct binding to the RAC3 promoter region.These findings suggest that RAC3 drives HCC progression through E2F1-mediated cell-cycle dysregulation.CONCLUSION This study identified RAC3 as a key HCC oncogenic driver;its overexpression links to poor prognosis/resistance.Targeting the RAC3/E2F1 axis offers a new therapy,which highlights RAC3 as a biomarker/target.
基金This project is supported by the Special Funds for Major Specialties of Shanghai Education Committee and the Natural Foundation ofShanghai City.
文摘This paper is concerned with the convergence rates of ergodic limits and approximation for regularized resolvent families for a linear Volterra integral equation. The results contain C 0-semigroups, cosine operator functions and α-times integrated resolvent family as special cases.
文摘Let and A be the generator of an -times resolvent family on a Banach space X. It is shown that the fractional Cauchy problem has maximal regularity on if and only if is of bounded semivariation on .
基金supported by The Final Achievement of the 13th Five-Year Plan of Philosophy and Social Sciences in Guangdong Province in 2020“Research on the Relationship Between Family Support,School Support and School Adaptation of Regular Primary School Students(No.:GD20XJY27).
文摘This paper aims to verify the family support situation for primary school children with intellectual disabilities learning in regular class and to explore various educational strategies to promote their development.A self-made questionnaire was used in this survey,and the parents of 380 intellectual disabled students were the subjects of this survey.It turns out that the overall family support for intellectual disabled children learning in regular class in China is good,but it is affected by the degree of obstacles.Factors such as grade,gender,and parental education had no significant effect on family support.It is the shared responsibility of the government,schools,and parents to promote the level of family support.Governments at all levels must implement family support projects,schools must carry out family education guidance to impart scientific parenting knowledge,and parents must take note of their own responsibilities,so as to promote the physical and mental development of children with intellectual disabilities.
基金This project was supported by TRAPOYT, the Key Project of Chinese Ministry of Education(104126) the NNSF of China(10371046)
文摘This article is concerned with the ill-posed Cauchy problem associated with a densely defined linear operator A in a Banach space. A family of weak regularizing operators is introduced. If the spectrum of A is contained in a sector of right-half complex plane and its resolvent is polynomially bounded, the weak regularization for such ill-posed Cauchy problem can be shown by using the quasi-reversibilky method and regularized semigroups. Finally, an example is given.
基金This project is supported by the Natural Science Foundation of China and Science Development Foundation of the Colleges and University of Shanghai.
文摘In this paper, α-times integrated C-regularized cosine functions and mild α-times integrated C-existence families of second order are introduced. Equivalences are proved among α-times integrated C-regularized cosine function for a linear operator A, C-wellposed of (α+1)-times abstract Cauchy problem and mild a -times integrated C-existence family of second order for A when the commutable condition is satisfied. In addition, if A = C-1AC, they are also equivalent to A generating the α -times integrated C-regularized cosine function. The characterization of an exponentially bounded mild α -times integrated C-existence family of second order is given out in terms of a Laplace transform.
文摘In this paper, we study the regularity of mild solution for the following fractional abstract Cauchy problem Dt αu(t)=Au(t)+f(t), t ∈ (0,T] u(0)= x0 on a Banach space X with order α ∈ (0,1), where the fractional derivative is understood in the sense of Caputo fractional derivatives. We show that if A generates an analytic α-times resolvent family on X and f ∈ Lp ([0,T];X) for some p > 1/α, then the mild solution to the above equation is in Cα-1/p[ò,T] for every ò > 0. Moreover, if f is H?lder continuous, then so are the Dt αu(t) and Au(t).
