Background Cell metabolism plays a pivotal role in tumor progression,and targeting cancer metabolism might effectively kill cancer cells.We aimed to investigate the role of hexokinases in prostate cancer(PCa)and ident...Background Cell metabolism plays a pivotal role in tumor progression,and targeting cancer metabolism might effectively kill cancer cells.We aimed to investigate the role of hexokinases in prostate cancer(PCa)and identify a crucial target for PCa treatment.Methods The Cancer Genome Atlas(TCGA)database,online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase(ADPGK)in PCa.The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo.Quantitative proteomics,metabolomics,and extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)tests were performed to evaluate the impact of ADPGK on PCa metabolism.The underlying mechanisms were explored through ADPGK overexpression and knockdown,co-immunoprecipitation(Co-IP),ECAR analysis and cell counting kit-8(CCK-8)assays.Results ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival(OS)in prostate adenocarcinoma(PRAD).Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs.non-PCa tissues.High ADPGK expression indicates worse survival outcomes,and ADPGK serves as an independent factor of biochemical recurrence.In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration,and ADPGK inhibition suppressed malignant phenotypes.Metabolomics,proteomics,and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa.Mechanistically,ADPGK binds aldolase C(ALDOC)to promote glycolysis via AMP-activated protein kinase(AMPK)phosphorylation.ALDOC was positively correlated with ADPGK,and high ALDOC expression was associated with worse survival outcomes in PCa.Conclusions In summary,ADPGK is a driving factor in PCa progression,and its high expression contributes to a poor prognosis in PCa patients.ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling,suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.展开更多
This study aimed to assess the role of prostate-specific antigen density(PSAD)and negative multiparametric magnetic resonance imaging(mpMRI)in predicting prostate cancer for biopsy-naive men based on a large cohort of...This study aimed to assess the role of prostate-specific antigen density(PSAD)and negative multiparametric magnetic resonance imaging(mpMRI)in predicting prostate cancer for biopsy-naive men based on a large cohort of the Chinese population.From a prostate biopsy database between March 2017 and July 2021,we retrospectively identified 240 biopsy-naive patients with negative prebiopsy mpMRI(Prostate Imaging Reporting and Data System version 2[PI-RADS v2]score<3).Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer(csPCa).Receiver operating characteristic(ROC)curve analysis and area under the ROC curve(AUC)were performed to assess the diagnostic accuracy.The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8%(201/240)and 90.8%(218/240),respectively.R0C curve analysis indicated that PSAD was the most promising predictor,with an AUC value of 0.786(95%confidence interval[CI]:0.699-0.874),and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa(odds ratio[0R]:10.99,95%CI:2.75-44.02,P<0.001).Combining negative mpMRI and PSAD below 0.20 ng ml^(-2)obviously increased the predictive value in excluding PCa(91.0%,101/111)or csPCa(100.0%,111/111).If a PSAD below 0.20 ng ml^(-2)was set as the criterion to omit biopsy,nearly 46.3%of patients(463 per 1000)with negative mpMRI could safely avoid unnecessary biopsy,with approximately 4.2%of patients(42 per 1000)at risk of missed diagnosis of PCa and no patients with csPCa missed.A PI-RADS v2 score<3 and a PSAD<0.20 ng ml^(-2)could be potential criteria for the Chinese population to omit prompt biopsy safely.展开更多
Fascinating with high specific capacity and moderate lithiation potential,SnO_(x)-based materials have been intensively investigated as one of the most promising anodes for lithium-ion batteries.However,due to poor cy...Fascinating with high specific capacity and moderate lithiation potential,SnO_(x)-based materials have been intensively investigated as one of the most promising anodes for lithium-ion batteries.However,due to poor cycling stability,sluggish reaction kinetics,and limited electrochemical reaction reversibility,the development of SnO_(x)-based anodes has been hindered.And the current preparation and modification routes for SnO_(x)-based anodes lack direct and specific illustration.Herein,modification routes for SnO_(x)-based anodes have been emphasized.Firstly,to provide more direct instructions,the tuning routes of morphological structure for SnO_(x)-based electrodes(including slurry-based and self-supported)have been thoroughly discussed from the preparation perspective.Secondly,according to the properties of SnO_(x)-based anodes,the phase structure design ideas have also been properly classified and organized for addressing chemical reaction kinetics or thermodynamic issues.Finally,for future-oriented studies,new insights into the development and commercialization prospects of SnO_(x)-based anodes are also provided.This review,with comprehensive information on SnO_(x)-based anodes,aims to bring more specific guidance and valuable inspiration for peer researchers who are promoting the application of SnO_(x)-based materials for energy conversion and storage devices.展开更多
Neoadjuvant chemotherapy(NAC)has shown promising results in patients with locally advanced penile cancer.However,no consensus exists on its applications for locally advanced penile cancer.Thus,it is unclear which kind...Neoadjuvant chemotherapy(NAC)has shown promising results in patients with locally advanced penile cancer.However,no consensus exists on its applications for locally advanced penile cancer.Thus,it is unclear which kind of chemotherapy regimen is the best choice.Consequently,a systematic search of PubMed,Web of Science,and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer.The Newcastle–Ottawa Scale was used to assess the risk of bias in each study.This study synthesized 14 published studies.The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response.In addition,the objective response rates(ORRs)and pathological complete response(pCR)rates were 0.57 and 0.11,respectively.The incidence of grade≥3 toxicity was 0.36.Subgroup analysis found that the ORR and pCR of the taxane–platinum(TP)regimen group performed better than those of the nontaxane–platinum(NTP)regimen group(0.57 vs 0.54 and 0.14 vs 0.07,respectively).Moreover,the TP regimen group had more frequent toxicity than the NTP regimen group(0.41 vs 0.26).However,further studies were warranted to confirm the findings.展开更多
Prostate cancer(PCa)is the second-most common cancer among men.Both active surveillance or watchful waiting(AS/WW)and focal laser ablation(FLA)can avoid the complications caused by radical treatment.How to make the ch...Prostate cancer(PCa)is the second-most common cancer among men.Both active surveillance or watchful waiting(AS/WW)and focal laser ablation(FLA)can avoid the complications caused by radical treatment.How to make the choice between these options in clinical practice needs further study.Therefore,this study aims to compare and analyze their effects based on overall survival(OS)and cancer-specific survival(CSS)to obtain better long-term benefits.We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010–2016.Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups.To eliminate bias,this study applied a series of sensitivity analyses.Moreover,Kaplan–Meier curves were plotted to obtain survival status.A total of 18841 patients with low-risk PCa were included,with a median of 36-month follow-up.According to the multivariate Cox proportional hazard regression,the FLA group presented inferior survival benefits in OS than the AS/WW group(hazard ratio[HR]:2.13,95%confidence interval[CI]:1.37–3.33,P<0.05).After adjusting for confounders,the result persisted(HR:1.69,95%CI:1.02–2.81,P<0.05).According to the results of the sensitivity analysis,the inverse probability of the treatment weighing model indicated the same result in OS.In conclusion,AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment.Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa.More relevant researches and data will be needed for further clarity.展开更多
基金National Key R&D Plan(2023YFC3403200)National Natural Science Foundation of China(82070784,81702536,81974099 and 82170785)+4 种基金Science&Technology Department of Sichuan Province,China(2022JDRC0040,21GJHZ0246)Young Investigator Award of Sichuan University 2017(2017SCU04A17)Sichuan University-Panzhihua Science and Technology Cooperation Special Fund(2020CDPZH-4)China Postdoctoral Science Foundation(2021M692306)Post-Doctor Research Project of West China Hospital of Sichuan University(2021HXBH025).
文摘Background Cell metabolism plays a pivotal role in tumor progression,and targeting cancer metabolism might effectively kill cancer cells.We aimed to investigate the role of hexokinases in prostate cancer(PCa)and identify a crucial target for PCa treatment.Methods The Cancer Genome Atlas(TCGA)database,online tools and clinical samples were used to assess the expression and prognostic role of ADP-dependent glucokinase(ADPGK)in PCa.The effect of ADPGK expression on PCa cell malignant phenotypes was validated in vitro and in vivo.Quantitative proteomics,metabolomics,and extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)tests were performed to evaluate the impact of ADPGK on PCa metabolism.The underlying mechanisms were explored through ADPGK overexpression and knockdown,co-immunoprecipitation(Co-IP),ECAR analysis and cell counting kit-8(CCK-8)assays.Results ADPGK was the only glucokinase that was both upregulated and predicted worse overall survival(OS)in prostate adenocarcinoma(PRAD).Clinical sample analysis demonstrated that ADPGK was markedly upregulated in PCa tissues vs.non-PCa tissues.High ADPGK expression indicates worse survival outcomes,and ADPGK serves as an independent factor of biochemical recurrence.In vitro and in vivo experiments showed that ADPGK overexpression promoted PCa cell proliferation and migration,and ADPGK inhibition suppressed malignant phenotypes.Metabolomics,proteomics,and ECAR and OCR tests revealed that ADPGK significantly accelerated glycolysis in PCa.Mechanistically,ADPGK binds aldolase C(ALDOC)to promote glycolysis via AMP-activated protein kinase(AMPK)phosphorylation.ALDOC was positively correlated with ADPGK,and high ALDOC expression was associated with worse survival outcomes in PCa.Conclusions In summary,ADPGK is a driving factor in PCa progression,and its high expression contributes to a poor prognosis in PCa patients.ADPGK accelerates PCa glycolysis and progression by activating ALDOC-AMPK signaling,suggesting that ADPGK might be an effective target and marker for PCa treatment and prognosis evaluation.
基金supported by the National Natural Science Foundation of China(grant No.81974099,82170785,81974098,82170784)programs from Science and Technology Department of Sichuan Province(grant No.21GJHZ0246)+2 种基金Young Investigator Award of Sichuan University 2017(grant No.2017SCU04A17)Technology Innovation Research and Development Project of Chengdu Science and Technology Bureau(No.2019-YF05-00296-SN)Sichuan University-Panzhihua science and technology cooperation special fund(No.2020CDPZH-4).
文摘This study aimed to assess the role of prostate-specific antigen density(PSAD)and negative multiparametric magnetic resonance imaging(mpMRI)in predicting prostate cancer for biopsy-naive men based on a large cohort of the Chinese population.From a prostate biopsy database between March 2017 and July 2021,we retrospectively identified 240 biopsy-naive patients with negative prebiopsy mpMRI(Prostate Imaging Reporting and Data System version 2[PI-RADS v2]score<3).Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer(csPCa).Receiver operating characteristic(ROC)curve analysis and area under the ROC curve(AUC)were performed to assess the diagnostic accuracy.The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8%(201/240)and 90.8%(218/240),respectively.R0C curve analysis indicated that PSAD was the most promising predictor,with an AUC value of 0.786(95%confidence interval[CI]:0.699-0.874),and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa(odds ratio[0R]:10.99,95%CI:2.75-44.02,P<0.001).Combining negative mpMRI and PSAD below 0.20 ng ml^(-2)obviously increased the predictive value in excluding PCa(91.0%,101/111)or csPCa(100.0%,111/111).If a PSAD below 0.20 ng ml^(-2)was set as the criterion to omit biopsy,nearly 46.3%of patients(463 per 1000)with negative mpMRI could safely avoid unnecessary biopsy,with approximately 4.2%of patients(42 per 1000)at risk of missed diagnosis of PCa and no patients with csPCa missed.A PI-RADS v2 score<3 and a PSAD<0.20 ng ml^(-2)could be potential criteria for the Chinese population to omit prompt biopsy safely.
基金financially supported by the National Natural Science Foundation of China(Nos.52071144,51831009 and 51621001)Guangzhou key research and development program(No.202103040001)。
文摘Fascinating with high specific capacity and moderate lithiation potential,SnO_(x)-based materials have been intensively investigated as one of the most promising anodes for lithium-ion batteries.However,due to poor cycling stability,sluggish reaction kinetics,and limited electrochemical reaction reversibility,the development of SnO_(x)-based anodes has been hindered.And the current preparation and modification routes for SnO_(x)-based anodes lack direct and specific illustration.Herein,modification routes for SnO_(x)-based anodes have been emphasized.Firstly,to provide more direct instructions,the tuning routes of morphological structure for SnO_(x)-based electrodes(including slurry-based and self-supported)have been thoroughly discussed from the preparation perspective.Secondly,according to the properties of SnO_(x)-based anodes,the phase structure design ideas have also been properly classified and organized for addressing chemical reaction kinetics or thermodynamic issues.Finally,for future-oriented studies,new insights into the development and commercialization prospects of SnO_(x)-based anodes are also provided.This review,with comprehensive information on SnO_(x)-based anodes,aims to bring more specific guidance and valuable inspiration for peer researchers who are promoting the application of SnO_(x)-based materials for energy conversion and storage devices.
基金This study was supported by grants from National Natural Science Foundation of China(No.82070784 and No.81974099)a grant from 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD18011)to HL.
文摘Neoadjuvant chemotherapy(NAC)has shown promising results in patients with locally advanced penile cancer.However,no consensus exists on its applications for locally advanced penile cancer.Thus,it is unclear which kind of chemotherapy regimen is the best choice.Consequently,a systematic search of PubMed,Web of Science,and EMBASE was performed in March 2021 to assess the efficacy and safety of NAC for the treatment of patients with locally advanced penile cancer.The Newcastle–Ottawa Scale was used to assess the risk of bias in each study.This study synthesized 14 published studies.The study revealed that patients who achieved an objective response to NAC obtained a better survival outcome compared with those who did not achieve an objective response.In addition,the objective response rates(ORRs)and pathological complete response(pCR)rates were 0.57 and 0.11,respectively.The incidence of grade≥3 toxicity was 0.36.Subgroup analysis found that the ORR and pCR of the taxane–platinum(TP)regimen group performed better than those of the nontaxane–platinum(NTP)regimen group(0.57 vs 0.54 and 0.14 vs 0.07,respectively).Moreover,the TP regimen group had more frequent toxicity than the NTP regimen group(0.41 vs 0.26).However,further studies were warranted to confirm the findings.
文摘Prostate cancer(PCa)is the second-most common cancer among men.Both active surveillance or watchful waiting(AS/WW)and focal laser ablation(FLA)can avoid the complications caused by radical treatment.How to make the choice between these options in clinical practice needs further study.Therefore,this study aims to compare and analyze their effects based on overall survival(OS)and cancer-specific survival(CSS)to obtain better long-term benefits.We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010–2016.Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups.To eliminate bias,this study applied a series of sensitivity analyses.Moreover,Kaplan–Meier curves were plotted to obtain survival status.A total of 18841 patients with low-risk PCa were included,with a median of 36-month follow-up.According to the multivariate Cox proportional hazard regression,the FLA group presented inferior survival benefits in OS than the AS/WW group(hazard ratio[HR]:2.13,95%confidence interval[CI]:1.37–3.33,P<0.05).After adjusting for confounders,the result persisted(HR:1.69,95%CI:1.02–2.81,P<0.05).According to the results of the sensitivity analysis,the inverse probability of the treatment weighing model indicated the same result in OS.In conclusion,AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment.Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa.More relevant researches and data will be needed for further clarity.
