Objective Allocation of human resources to address inequalities in the public health system has increasingly attracted societal and political attention.Using the Centers for Disease Control and Prevention(CDCs)system ...Objective Allocation of human resources to address inequalities in the public health system has increasingly attracted societal and political attention.Using the Centers for Disease Control and Prevention(CDCs)system of China as an example,we evaluated inequality in the public health workforce distribution across different regions in China between 2008 and 2017,with the aim of providing information for policymakers to support resource allocation and address growing health inequities.Methods We used three standard public health workforce inequality indices-Gini coefficient,Theil L,and Theil T-and spatial autocorrelation analysis to explore spatial clusters of the workforce in different provinces,visualized with geographical tools.Results The aggregate workforce-to-population ratio decreased from 1.47 to 1.42 per 10,000 population from 2008 to 2017,and was consistently lower than the National Health Commission’s(NHC)recommended critical shortage threshold of 1.75.The workforce distribution inequality indices varied by regional socioeconomic and health system development.Geographic clustering of CDCs workforce distribution was evident,with H–H and L–L clusters in western China and the Guangdong-Fujian region,respectively.Conclusions Our study addressed key issues for government and policymakers in allocation of public health human resources.There is an urgent need for careful identification of analytic questions that will help carry out public health functions in the new era,alongside policy implications for an equitable distribution of the public health workforce focusing on the western region and low–low cluster areas.展开更多
In order to regenerate myocardium and provide appropriate mechanical support after a heart attack,jersey,tuck and rib stitch structures were knitted from polylactic acid(PLA)yarns to fabricate a cardiac patch,which mi...In order to regenerate myocardium and provide appropriate mechanical support after a heart attack,jersey,tuck and rib stitch structures were knitted from polylactic acid(PLA)yarns to fabricate a cardiac patch,which mimicked the mechanical properties of myocardium in both directions.Cardiosphere-derived cells(CDCs) were seeded on these PLA patch fabrics,and using scanning electron microscopy(SEM) characterization and an MTT assay the cells proliferated and attached successfully to the PLA fabrics.Based on the results,the rib stitch structure is the most promising candidate for fabricating cardiac patches due to its high elasticity and its ability to promote cell proliferation.展开更多
Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential ...Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.展开更多
The budding yeast Saccharomyces cerevisiae is a powerful model system for studying the cell polarity establishment.The cell polarization process is regulated by signaling molecules,which are initially distributed in t...The budding yeast Saccharomyces cerevisiae is a powerful model system for studying the cell polarity establishment.The cell polarization process is regulated by signaling molecules,which are initially distributed in the cytoplasm and then recruited to a proper location on the cell membrane in response to spatial cues or spontaneously.Polarization of these signaling molecules involves complex regulation,so the mathematical models become a useful tool to investigate the mechanism behind the process.In this review,we discuss how mathematical modeling has shed light on different regulations in the cell polarization.We also propose future applications for the mathematical modeling of cell polarization and morphogenesis.展开更多
目的:双特异性酪氨酸磷酸化调节激酶,也称CDC样激酶(cell division cycle like kinases,CDC-like kinases,CLK),是一种双特异性蛋白激酶,其参与神经系统疾病、代谢异常、肿瘤等多个病理及生理过程,其中CLK3参与肝癌、乳腺癌等多种肿瘤...目的:双特异性酪氨酸磷酸化调节激酶,也称CDC样激酶(cell division cycle like kinases,CDC-like kinases,CLK),是一种双特异性蛋白激酶,其参与神经系统疾病、代谢异常、肿瘤等多个病理及生理过程,其中CLK3参与肝癌、乳腺癌等多种肿瘤的发生和发展,但其在结直肠癌中的表达情况及临床意义尚无相关报道。本研究通过挖掘肿瘤在线数据库,探讨CLK3在结直肠癌中的表达及临床意义。方法:利用基因表达谱交互分析2(Gene Expression Profiling Interactive Analysis 2,GEPIA2)数据库及GEO2R工具对CLK3在肿瘤间及结直肠癌组织和正常组织间作差异分析,获取差异表达结果后利用UALCN(The University of Alabama at Birmingham Cancer Data Analysis Portal)数据库对CLK3表达差异组作Kaplan-Meier生存分析。利用LinkedOmics数据库对CLK3进行共表达分析,并筛选出与之呈正相关及负相关的各50个基因,然后对获取的100个基因进行基因本体(gene ontology,GO)和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,同时利用TIMER2.0数据库对CLK3进行免疫相关分析。在组织表达层面,利用人类蛋白质图谱(Human Protein Atlas,HPA)数据库查询CLK3在结直肠癌与正常肠道组织的免疫组织化学标本,分析其表达差异。结果:在UALCN数据库中,与正常组织比较,CLK3在结肠癌组织中低表达(P<0.01),而在直肠癌组织中表达差异无统计学意义(P>0.05)。CLK3的表达水平与结直肠癌患者的预后显著相关(P<0.05),表现为其高表达与不良预后相关。GO与KEGG通路富集结果显示:CLK3共表达基因富集于抗原肽呈递、物质代谢合成过程、转录调节过程的酶反应、γ干扰素介导的信号通路、Wnt信号通路及肠道免疫炎症过程等。相关性分析显示:结肠癌中CLK3表达与BRAF、HERS、NTRK1、PIK3CA基因突变相关,直肠癌中CLK3表达与BRAF和PIK3CA基因突变相关。进一步免疫浸润分析结果显示:在结肠癌中,CLK3的表达水平与CD8^(+)T细胞、CD4^(+)T细胞、中性粒细胞和树突状细胞的浸润水平呈正相关(均P<0.05);在直肠癌中,CLK3的表达水平与CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润水平呈正相关(均P<0.05)。在免疫组织化学染色切片中,结肠癌和直肠癌CLK3蛋白表达水平均低于正常结肠组织(均P<0.05)。结论:CLK3在结直肠癌中存在差异表达,是结直肠癌生存预后的指标,有望成为结直肠癌的预后评估和临床治疗的有效靶点之一。展开更多
Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation...Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.展开更多
基金funded by China CDC’s Public Health and Emergency Response Mechanism Programme[131031001000150001]。
文摘Objective Allocation of human resources to address inequalities in the public health system has increasingly attracted societal and political attention.Using the Centers for Disease Control and Prevention(CDCs)system of China as an example,we evaluated inequality in the public health workforce distribution across different regions in China between 2008 and 2017,with the aim of providing information for policymakers to support resource allocation and address growing health inequities.Methods We used three standard public health workforce inequality indices-Gini coefficient,Theil L,and Theil T-and spatial autocorrelation analysis to explore spatial clusters of the workforce in different provinces,visualized with geographical tools.Results The aggregate workforce-to-population ratio decreased from 1.47 to 1.42 per 10,000 population from 2008 to 2017,and was consistently lower than the National Health Commission’s(NHC)recommended critical shortage threshold of 1.75.The workforce distribution inequality indices varied by regional socioeconomic and health system development.Geographic clustering of CDCs workforce distribution was evident,with H–H and L–L clusters in western China and the Guangdong-Fujian region,respectively.Conclusions Our study addressed key issues for government and policymakers in allocation of public health human resources.There is an urgent need for careful identification of analytic questions that will help carry out public health functions in the new era,alongside policy implications for an equitable distribution of the public health workforce focusing on the western region and low–low cluster areas.
基金the College of Textiles,North Carolina State University,Raleigh,USA“111 Project” Biomedical Textile Materials Science and Technology,China(No.B07024)
文摘In order to regenerate myocardium and provide appropriate mechanical support after a heart attack,jersey,tuck and rib stitch structures were knitted from polylactic acid(PLA)yarns to fabricate a cardiac patch,which mimicked the mechanical properties of myocardium in both directions.Cardiosphere-derived cells(CDCs) were seeded on these PLA patch fabrics,and using scanning electron microscopy(SEM) characterization and an MTT assay the cells proliferated and attached successfully to the PLA fabrics.Based on the results,the rib stitch structure is the most promising candidate for fabricating cardiac patches due to its high elasticity and its ability to promote cell proliferation.
文摘Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.
文摘The budding yeast Saccharomyces cerevisiae is a powerful model system for studying the cell polarity establishment.The cell polarization process is regulated by signaling molecules,which are initially distributed in the cytoplasm and then recruited to a proper location on the cell membrane in response to spatial cues or spontaneously.Polarization of these signaling molecules involves complex regulation,so the mathematical models become a useful tool to investigate the mechanism behind the process.In this review,we discuss how mathematical modeling has shed light on different regulations in the cell polarization.We also propose future applications for the mathematical modeling of cell polarization and morphogenesis.
文摘目的:双特异性酪氨酸磷酸化调节激酶,也称CDC样激酶(cell division cycle like kinases,CDC-like kinases,CLK),是一种双特异性蛋白激酶,其参与神经系统疾病、代谢异常、肿瘤等多个病理及生理过程,其中CLK3参与肝癌、乳腺癌等多种肿瘤的发生和发展,但其在结直肠癌中的表达情况及临床意义尚无相关报道。本研究通过挖掘肿瘤在线数据库,探讨CLK3在结直肠癌中的表达及临床意义。方法:利用基因表达谱交互分析2(Gene Expression Profiling Interactive Analysis 2,GEPIA2)数据库及GEO2R工具对CLK3在肿瘤间及结直肠癌组织和正常组织间作差异分析,获取差异表达结果后利用UALCN(The University of Alabama at Birmingham Cancer Data Analysis Portal)数据库对CLK3表达差异组作Kaplan-Meier生存分析。利用LinkedOmics数据库对CLK3进行共表达分析,并筛选出与之呈正相关及负相关的各50个基因,然后对获取的100个基因进行基因本体(gene ontology,GO)和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,同时利用TIMER2.0数据库对CLK3进行免疫相关分析。在组织表达层面,利用人类蛋白质图谱(Human Protein Atlas,HPA)数据库查询CLK3在结直肠癌与正常肠道组织的免疫组织化学标本,分析其表达差异。结果:在UALCN数据库中,与正常组织比较,CLK3在结肠癌组织中低表达(P<0.01),而在直肠癌组织中表达差异无统计学意义(P>0.05)。CLK3的表达水平与结直肠癌患者的预后显著相关(P<0.05),表现为其高表达与不良预后相关。GO与KEGG通路富集结果显示:CLK3共表达基因富集于抗原肽呈递、物质代谢合成过程、转录调节过程的酶反应、γ干扰素介导的信号通路、Wnt信号通路及肠道免疫炎症过程等。相关性分析显示:结肠癌中CLK3表达与BRAF、HERS、NTRK1、PIK3CA基因突变相关,直肠癌中CLK3表达与BRAF和PIK3CA基因突变相关。进一步免疫浸润分析结果显示:在结肠癌中,CLK3的表达水平与CD8^(+)T细胞、CD4^(+)T细胞、中性粒细胞和树突状细胞的浸润水平呈正相关(均P<0.05);在直肠癌中,CLK3的表达水平与CD4^(+)T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润水平呈正相关(均P<0.05)。在免疫组织化学染色切片中,结肠癌和直肠癌CLK3蛋白表达水平均低于正常结肠组织(均P<0.05)。结论:CLK3在结直肠癌中存在差异表达,是结直肠癌生存预后的指标,有望成为结直肠癌的预后评估和临床治疗的有效靶点之一。
文摘Background: Omicron JN.1 has become the dominant SARS-CoV-2 variant in recent months. JN.1 has the highest number of amino acid mutations in its receptor binding domain (RBD) and has acquired a hallmark L455S mutation. The immune evasion capability of JN.1 is a subject of scientific investigation. The US CDC used SGTF of TaqPath COVID-19 Combo Kit RT-qPCR as proxy indicator of JN.1 infections for evaluation of the effectiveness of updated monovalent XBB.1.5 COVID-19 vaccines against JN.1 and recommended that all persons aged ≥ 6 months should receive an updated COVID-19 vaccine dose. Objective: Recommend Sanger sequencing instead of proxy indicator to diagnose JN.1 infections to generate the data based on which guidelines are made to direct vaccination policies. Methods: The RNA in nasopharyngeal swab specimens from patients with clinical respiratory infection was subjected to nested RT-PCR, targeting a 398-base segment of the N-gene and a 445-base segment of the RBD of SARS-CoV-2 for amplification. The nested PCR amplicons were sequenced. The DNA sequences were analyzed for amino acid mutations. Results: The N-gene sequence showed R203K, G204R and Q229K, the 3 mutations associated with Omicron BA.2.86 (+JN.1). The RBD sequence showed 24 of the 26 known amino acid mutations, including the hallmark L455S mutation for JN.1 and the V483del for BA.2.86 lineage. Conclusions: Sanger sequencing of a 445-base segment of the SARS-CoV-2 RBD is useful for accurate determination of emerging variants. The CDC may consider using Sanger sequencing of the RBD to diagnose JN.1 infections for statistical analysis in making vaccination policies.
