BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflamma...BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflammatory bowel disease.Despite current treatments,survival rates for advanced CRC remain low,highlighting the need for better therapeutic strategies.AIM To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14(KIF14)expression within CRC specimens.Additionally,this study aims to investigate the interaction between nitidine chloride(NC)and KIF14,considering their potential as therapeutic targets.METHODS The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining.The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference(SMD)for KIF14 mRNA levels.The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves,along with measures of sensitivity,specificity,and likelihood ratios.Additionally,clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC.Survival analysis established the prognostic value of KIF14 in CRC.The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis,and molecular docking was utilized to explore the targeting affinity between NC and KIF14.RESULTS KIF14 was highly expressed in 208 CRC patients.Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples,with an SMD of 1.92(95%CI:1.49-2.35).The area under the curve was 0.94(95%CI:0.92-0.96),with a sensitivity of 0.85(95%CI:0.78-0.90)and a specificity of 0.90(95%CI:0.85-0.93).The positive and negative likelihood ratios were 8.38(95%CI:5.39-13.02)and 0.17(95%CI:0.11-0.26),respectively.At the single-cell level,significant overexpression of KIF14 was observed in CRC cells(P<0.001),with 35 CRC cell lines dependent on KIF14 for growth.The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets(P<0.05).Binding energy calculations indicated that KIF14 is a potential target for NC(binding energy:10.3 kcal/mol).CONCLUSION KIF14 promotes the growth of CRC cells and acts as an oncogenic factor,potentially serving as a therapeutic target for NC in the treatment of CRC.展开更多
BACKGROUND The stearoyl-coenzyme A desaturase(SCD)gene influences colorectal cancer(CRC)pathogenesis,with its expression linked to tumor cell survival and resistance,necessitating further investigation into its role i...BACKGROUND The stearoyl-coenzyme A desaturase(SCD)gene influences colorectal cancer(CRC)pathogenesis,with its expression linked to tumor cell survival and resistance,necessitating further investigation into its role in CRC.AIM To explore the clinical and pathological significance of SCD expression in CRC tissues and to evaluate the affinity between nitidine chloride(NC)and SCD as a target.METHODS Multi-center high-throughput data related to CRC were integrated to calculate the standardized mean difference of SCD mRNA expression levels.Immunohistochemical staining results,Clustered Regularly Interspaced Short Palindromic Repeats knockout screening results of cell growth,and single-cell sequencing were employed to verify the significance of SCD expression in CRC.The clinical and pathological significance of SCD was assessed using pooled receiver operating characteristic curves,sensitivity,specificity,and likelihood ratios.The molecular mechanism of NC against CRC was clarified using the SwissTarget Prediction and functional enrichment,and molecular docking techniques were utilized to explore the targeting affinity between NC and SCD.RESULTS Data from 18 platforms,including 2482 CRC samples and 1334 non-cancerous colorectal tissue controls.SCD expression was significantly upregulated in CRC,with a standardized mean difference of 2.05[95%confidence interval(CI):1.69-2.41].The area under the pooled receiver operating characteristic curve was 0.95(95%CI:0.92-0.96),with a sensitivity of 0.86(95%CI:0.81-0.90)and a specificity of 0.90(95%CI:0.87-0.93).Positive and negative likelihood ratios were 9.02(95%CI:6.49-12.51)and 0.15(95%CI:0.10-0.22),respectively.High SCD protein expression was noted in 208 CRC patients,significantly associated with vascular invasion(P<0.001).At the singlecell level,SCD was significantly overexpressed in CRC cells(P<0.001).A total of 33 CRC cell lines depended on SCD for growth.The potential mechanism of NC against CRC might involve modulation of the cell cycle,positioning SCD as a potential target for NC.CONCLUSION SCD promotes CRC cell growth and thus acts as an oncogenic factor,making it a potential therapeutic target for NC in CRC treatment.展开更多
Many scholars have conducted visual analyses of urban skylines, but little attention has been paid to the quantitative measures regarding specific design elements within the skyline. This article aims to help urban de...Many scholars have conducted visual analyses of urban skylines, but little attention has been paid to the quantitative measures regarding specific design elements within the skyline. This article aims to help urban designers and regulators improve the skyline and investigate which factors can make urban skylines more pleasant for people. Computer generated images of skylines are tested for three factors including greenery, layering, and landmarks. For the data collection, a questionnaire was used, as one of the simple and effective methods to gather results. The authors use statistics as a method of measuring the degree of people's preferences. The study finds that the proportions of landmarks in the overall skyline, the height of layers, and the percentage of greenery deserve special attention. The authors also discuss the current problems of skyline design in typical Chinese cities according to the above findings.展开更多
基金Natural Science Foundation of Shandong Province,No.ZR2020QH185Scientific Research Nurturing Fund of The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,No.QYPY2020NSFC0803+2 种基金Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220415Guangxi Medical University Teacher Teaching Ability Development Project,No.2022JFA02Guangxi Medical University Undergraduate Education and Teaching Reform Project,No.2023Y05.
文摘BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflammatory bowel disease.Despite current treatments,survival rates for advanced CRC remain low,highlighting the need for better therapeutic strategies.AIM To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14(KIF14)expression within CRC specimens.Additionally,this study aims to investigate the interaction between nitidine chloride(NC)and KIF14,considering their potential as therapeutic targets.METHODS The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining.The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference(SMD)for KIF14 mRNA levels.The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves,along with measures of sensitivity,specificity,and likelihood ratios.Additionally,clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC.Survival analysis established the prognostic value of KIF14 in CRC.The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis,and molecular docking was utilized to explore the targeting affinity between NC and KIF14.RESULTS KIF14 was highly expressed in 208 CRC patients.Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples,with an SMD of 1.92(95%CI:1.49-2.35).The area under the curve was 0.94(95%CI:0.92-0.96),with a sensitivity of 0.85(95%CI:0.78-0.90)and a specificity of 0.90(95%CI:0.85-0.93).The positive and negative likelihood ratios were 8.38(95%CI:5.39-13.02)and 0.17(95%CI:0.11-0.26),respectively.At the single-cell level,significant overexpression of KIF14 was observed in CRC cells(P<0.001),with 35 CRC cell lines dependent on KIF14 for growth.The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets(P<0.05).Binding energy calculations indicated that KIF14 is a potential target for NC(binding energy:10.3 kcal/mol).CONCLUSION KIF14 promotes the growth of CRC cells and acts as an oncogenic factor,potentially serving as a therapeutic target for NC in the treatment of CRC.
基金Supported by Natural Science Foundation of Shandong Province,No.ZR2020QH185Scientific Research Nurturing Fund of the First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,No.QYPY2020NSFC0803Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z20210442.
文摘BACKGROUND The stearoyl-coenzyme A desaturase(SCD)gene influences colorectal cancer(CRC)pathogenesis,with its expression linked to tumor cell survival and resistance,necessitating further investigation into its role in CRC.AIM To explore the clinical and pathological significance of SCD expression in CRC tissues and to evaluate the affinity between nitidine chloride(NC)and SCD as a target.METHODS Multi-center high-throughput data related to CRC were integrated to calculate the standardized mean difference of SCD mRNA expression levels.Immunohistochemical staining results,Clustered Regularly Interspaced Short Palindromic Repeats knockout screening results of cell growth,and single-cell sequencing were employed to verify the significance of SCD expression in CRC.The clinical and pathological significance of SCD was assessed using pooled receiver operating characteristic curves,sensitivity,specificity,and likelihood ratios.The molecular mechanism of NC against CRC was clarified using the SwissTarget Prediction and functional enrichment,and molecular docking techniques were utilized to explore the targeting affinity between NC and SCD.RESULTS Data from 18 platforms,including 2482 CRC samples and 1334 non-cancerous colorectal tissue controls.SCD expression was significantly upregulated in CRC,with a standardized mean difference of 2.05[95%confidence interval(CI):1.69-2.41].The area under the pooled receiver operating characteristic curve was 0.95(95%CI:0.92-0.96),with a sensitivity of 0.86(95%CI:0.81-0.90)and a specificity of 0.90(95%CI:0.87-0.93).Positive and negative likelihood ratios were 9.02(95%CI:6.49-12.51)and 0.15(95%CI:0.10-0.22),respectively.High SCD protein expression was noted in 208 CRC patients,significantly associated with vascular invasion(P<0.001).At the singlecell level,SCD was significantly overexpressed in CRC cells(P<0.001).A total of 33 CRC cell lines depended on SCD for growth.The potential mechanism of NC against CRC might involve modulation of the cell cycle,positioning SCD as a potential target for NC.CONCLUSION SCD promotes CRC cell growth and thus acts as an oncogenic factor,making it a potential therapeutic target for NC in CRC treatment.
基金supported by a soft science research grant (No.2013-R2-43) from the Science and Technology Program funded by the Ministry of Housing and Urban-Rural Development of China
文摘Many scholars have conducted visual analyses of urban skylines, but little attention has been paid to the quantitative measures regarding specific design elements within the skyline. This article aims to help urban designers and regulators improve the skyline and investigate which factors can make urban skylines more pleasant for people. Computer generated images of skylines are tested for three factors including greenery, layering, and landmarks. For the data collection, a questionnaire was used, as one of the simple and effective methods to gather results. The authors use statistics as a method of measuring the degree of people's preferences. The study finds that the proportions of landmarks in the overall skyline, the height of layers, and the percentage of greenery deserve special attention. The authors also discuss the current problems of skyline design in typical Chinese cities according to the above findings.
