The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analys...The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analysis showed that Notch1 expression was higher in ICC tissues than in normal biliary epithelial cells.Stable transfection of Notchl receptor intracellular domain(NICD1)by hydrodynamic tail vein injection induced ICC formation in mice.Western blotting confirmed that Notchl signaling was activated in human ICC cell lines and mouse ICC tissues.Silencing Notchl with specific short interfering RNA(siRNA)inhibited the proliferation of ICC cells.Flow cytometry and Western blotting indicated that apoptosis was induced in Notchl-silenced ICC cells compared with controls.Additionally,Notchl silencing was associated with the inhibition of hairy and enhancer of split-1(Hes1)and activation of the phosphatase and tensin homolog(PTEN)/p53 pathway.Taken together,these data suggest that Notchl drives ICC formation and proliferation;downregulation of Notchl induces apoptosis in ICC cells;Notchl signaling may serve as a novel therapeutic target for the treatment of ICC.展开更多
Precise and spatiotemporal control over the pesticide remains to be a challenge.More efficient controlled release systems(CRSs)have been developed to support the precise delivery of active ingredients.Herein,we incorp...Precise and spatiotemporal control over the pesticide remains to be a challenge.More efficient controlled release systems(CRSs)have been developed to support the precise delivery of active ingredients.Herein,we incorporated the photoremovable protecting groups(PRPGs)into phenamacril(PHE)and obtained two photo-responsive fungicides of NV-PHE and DEACM-PHE.The 4,5-dimethoxy-o-nitrobenzyl(NV)or 7-diethylaminocoumarin(DEACM)-caged PHE could release the active molecule PHE after irradiation of UV light and blue light,respectively.Optical properties and in-vitro/vivo fungicidal activities of NV-PHE and DEACM-PHE demonstrated the feasibility for light controlled release of PHE.DEACM-PHE could release 98%PHE by illumination of blue light.The irradiated DEACM-PHE could preserve the similar bioactivity of PHE,and significantly improve the in-vitro/vivo fungicidal activities compared to the non-irradiated DEACM-PHE.The optical controlled release of PHE from DEACM-PHE enabled the precise and spatiotemporal delivery of PHE,diversifying the development of CRSs for pesticide,and providing environmentfriendly agricultural applications with high pesticide efficiency.展开更多
Objective:To investigate the effect of acupuncture onset time and synaptic structure in two different models of depression.Methods:A total of 150 healthy male adult SPF C57BL/6J mice were divided into five time-point ...Objective:To investigate the effect of acupuncture onset time and synaptic structure in two different models of depression.Methods:A total of 150 healthy male adult SPF C57BL/6J mice were divided into five time-point groups:1 h,3 h,6 h,12 h and 24 h.Each time-point group was further divided into three groups:the model,scopolamine and acupuncture groups with 10 rats each.Rats were given forced swimming stimulation(15 min,once)before the intervention.A total of 200 healthy male adult specific pathogen-free(SPF)Sprague-Dawley(SD)rats were divided into 30 normal rats,and 170 modelling ones.A total of 90 rats were successfully modeled,and were randomly divided into three time-point groups:1 h,6 h and 24 h.And each time-point group was further divided into the normal,model,scopolamine,and acupuncture group.Chronic unpredictable mild stress(CUMS)combined with individual feeding was used to establish the depressed rat model.The sucrose preference test(SPT)and open field test(OFT)were used to evaluate the success of the model.There were 10 rats in each group.The acupuncture intervention was performed once for 20 min on"Baihui(GV20)","Yintang(GV29)","Hegu(LI4)",and"Taichong(LR3)"without any other operations for the corresponding animals.Other groups were given corresponding medications.According to different time points,the forced swimming test(FST)was conducted in mice,and the FST and novelty-suppressed feeding test(NSFT)were measured in rats.Monoamine neurotransmitters(NE,DA,DOPAC,5-HT,5-HIAA,HVA)in the prefrontal cortex and hippocampus were detected with high performance liquid chromatography(HPLC).The expression of synapsin I,PSD95,p-mTOR,mTOR,and BDNF in the prefrontal cortex and hippocampus was determined by western blot.Results:At the 1 h time point,compared with the model group,the immobility time was significantly decreased in the acupuncture group(P<0.05).At 3 h,6 h,12 h,and 24 h,compared with the model group,the immobility time was significantly reduced in both scopolamine and acupuncture groups(P<0.05).At the 1 h time point,compared with the normal group,the immobility time of FST and the latency to feed were significantly increased in the model group(P<0.05).Compared with the model group,the immobility time of FST showed a significant reduction in the acupuncture group(P<0.05).At the 6h and 24 h time points,compared with the normal group,the immobility time of FST and the latency to feed were significantly increased in the model group(P<0.05).Compared with the model group,the immobility time of FST was significantly decreased in the scopolamine and acupuncture groups(P<0.05).At the 1 h and 24 h time points,compared with the normal group,the expression levels of 5-HT,5-HIAA,NE,DA,DOPAC,and HVA of the prefrontal cortical and hippocampal tissues were significantly reduced in the model group(P<0.05).At the 1 h and 24 h time points,compared with the model group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the prefrontal cortex were significantly increased in the acupuncture group(P<0.05).At the 1 h and 24 h time points,compared with the normal group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the prefrontal cortex were significantly reduced in the model group(P<0.05).Compared with the model group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the prefrontal cortex were significantly increased in the acupuncture group(P<0.05).At the 1 h and 24 h time points,compared with the normal group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the hippocampal tissues were significantly reduced in the model group(P<0.05).Compared with the model group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the hippocampus were not significantly different in the acupuncture group(P>0.05).Conclusion:Acupuncture may play a rapid antidepressant effect by increasing the expression of synaptic plasticity proteins in the prefrontal cortex.展开更多
Background: Neuroblastoma is one common pediatric malignancy notorious forhigh temporal and spatial heterogeneities. More than half of its patients developdistant metastases involving vascularized organs, especially t...Background: Neuroblastoma is one common pediatric malignancy notorious forhigh temporal and spatial heterogeneities. More than half of its patients developdistant metastases involving vascularized organs, especially the bone marrow. It isthus necessary to have an economical, noninvasive method without muchradiation for follow‐ups. Radiomics has been used in many cancers to assistaccurate diagnosis but not yet in bone marrow metastasis in neuroblastoma.Methods: A total of 182 patients with neuroblastoma were retrospectivelycollected and randomly divided into the training and validation sets. Fivehundredand seventy‐two radiomics features were extracted from magneticresonance imaging, among which 41 significant ones were selected via T‐testfor model development. We attempted 13 machine‐learning algorithms andeventually chose three best‐performed models. The integrative performanceevaluations are based on the area under the curves (AUCs), calibration curves,risk deciles plots, and other indexes.Results: Extreme gradient boosting, random forest (RF), and adaptiveboosting were the top three to predict bone marrow metastases in neuroblastoma while RF was the most accurate one. Its AUC was 0.90(0.86–0.93), F1 score was 0.82, sensitivity was 0.76, and negative predictivevalue was 0.79 in the training set. The values were 0.82 (0.71–0.93), 0.80,0.75, and 0.92 in the validation set, respectively.Conclusions: Radiomics models are likely to contribute more to metastaticdiagnoses and the formulation of personalized healthcare strategies in clinics.It has great potential of being a revolutionary method to replace traditionalinterventions in the future.展开更多
To the Editor:Wilms tumor,or nephroblastoma,is the most frequently diagnosed pediatric kidney cancer,accounting for>90%of all renal tumors in children 1–7 years old,and the disease may be related to genetic factor...To the Editor:Wilms tumor,or nephroblastoma,is the most frequently diagnosed pediatric kidney cancer,accounting for>90%of all renal tumors in children 1–7 years old,and the disease may be related to genetic factors.^([1])As an emerging research spot,the epitranscriptome has been implicated in different RNA modifications in human diseases,including cancers.[2]Methyltransferaselike 1(METTL1),a critical RNA N7-methylguanosine(m7G)methyltransferase,can catalyze the formation of a m7G modification(mostly at nucleotide position 46 in the variable region of transfer RNAs[tRNAs])by complexing with WD repeat domain 4(WDR4).Depending on the different positions,the tRNA m7G modifications have various functions.展开更多
Background:It has been observed that cancer and venous thromboembolism(VTE)are associated,but anticancer therapy may violate the causality.Therefore,this study aimed to elucidate the causal relationship of various can...Background:It has been observed that cancer and venous thromboembolism(VTE)are associated,but anticancer therapy may violate the causality.Therefore,this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization(MR).Methods:Three MR methods were used to estimate causal effects:Inverse variance weighted(IVW),MR-Egger and weighted median.Sensitivity analyses included Cochran's Q-test,MR-Egger intercept test and MRPRESSO.Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients.Results:The primary IVW approach showed that non-Hodgkin's lymphoma(NHL)might increase the risk of VTE(odds ratio[OR]:1.20,95%confidence interval[95%CI]:1.00–1.44,p=0.045),while melanoma possibly reduced the risk of VTE(OR:0.89,95%CI:0.82–0.97,p=0.006),although there was no significance after adjustment for multiple testing.No association was observed between VTE risk and other site-specific cancers.Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients.Conclusions:Our findings suggested that genetically predicted NHL was associated with higher VTE risk,whereas melanoma had lower VTE risk compared with other site-specific cancers.Moreover,this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.展开更多
基金the National Natural Science Foundation of China(No.81801621,No.81572723,No.81872253).
文摘The molecular mechanisms underlying the development of intrahepatic cholangiocarcinoma(ICC)are not clear yet.In this study,we investigated the involvement of Notch1 in the development of ICC.The cDNA microarray analysis showed that Notch1 expression was higher in ICC tissues than in normal biliary epithelial cells.Stable transfection of Notchl receptor intracellular domain(NICD1)by hydrodynamic tail vein injection induced ICC formation in mice.Western blotting confirmed that Notchl signaling was activated in human ICC cell lines and mouse ICC tissues.Silencing Notchl with specific short interfering RNA(siRNA)inhibited the proliferation of ICC cells.Flow cytometry and Western blotting indicated that apoptosis was induced in Notchl-silenced ICC cells compared with controls.Additionally,Notchl silencing was associated with the inhibition of hairy and enhancer of split-1(Hes1)and activation of the phosphatase and tensin homolog(PTEN)/p53 pathway.Taken together,these data suggest that Notchl drives ICC formation and proliferation;downregulation of Notchl induces apoptosis in ICC cells;Notchl signaling may serve as a novel therapeutic target for the treatment of ICC.
基金This work was financially supported by the Natural Science Foundation of China(Nos.21877039,32072441)National Key Research and Development Program of China(No.2018YFD0200100)Innovation Program of Shanghai Municipal Education Commission(No.2017-01-07-00-02-E00037).
文摘Precise and spatiotemporal control over the pesticide remains to be a challenge.More efficient controlled release systems(CRSs)have been developed to support the precise delivery of active ingredients.Herein,we incorporated the photoremovable protecting groups(PRPGs)into phenamacril(PHE)and obtained two photo-responsive fungicides of NV-PHE and DEACM-PHE.The 4,5-dimethoxy-o-nitrobenzyl(NV)or 7-diethylaminocoumarin(DEACM)-caged PHE could release the active molecule PHE after irradiation of UV light and blue light,respectively.Optical properties and in-vitro/vivo fungicidal activities of NV-PHE and DEACM-PHE demonstrated the feasibility for light controlled release of PHE.DEACM-PHE could release 98%PHE by illumination of blue light.The irradiated DEACM-PHE could preserve the similar bioactivity of PHE,and significantly improve the in-vitro/vivo fungicidal activities compared to the non-irradiated DEACM-PHE.The optical controlled release of PHE from DEACM-PHE enabled the precise and spatiotemporal delivery of PHE,diversifying the development of CRSs for pesticide,and providing environmentfriendly agricultural applications with high pesticide efficiency.
基金Supported by the National Natural Science Funds(82074522,U23A20507)Guangzhou Science and Technology Planning Project(202102010247)+1 种基金the Natural Science Foundation of Guangdong Province(2021A1515011464,2019A1515012043)Research Fund for Bajian Talents of Guangdong Provincial Hospital of Chinese Medicine(BJ2022KY10)。
文摘Objective:To investigate the effect of acupuncture onset time and synaptic structure in two different models of depression.Methods:A total of 150 healthy male adult SPF C57BL/6J mice were divided into five time-point groups:1 h,3 h,6 h,12 h and 24 h.Each time-point group was further divided into three groups:the model,scopolamine and acupuncture groups with 10 rats each.Rats were given forced swimming stimulation(15 min,once)before the intervention.A total of 200 healthy male adult specific pathogen-free(SPF)Sprague-Dawley(SD)rats were divided into 30 normal rats,and 170 modelling ones.A total of 90 rats were successfully modeled,and were randomly divided into three time-point groups:1 h,6 h and 24 h.And each time-point group was further divided into the normal,model,scopolamine,and acupuncture group.Chronic unpredictable mild stress(CUMS)combined with individual feeding was used to establish the depressed rat model.The sucrose preference test(SPT)and open field test(OFT)were used to evaluate the success of the model.There were 10 rats in each group.The acupuncture intervention was performed once for 20 min on"Baihui(GV20)","Yintang(GV29)","Hegu(LI4)",and"Taichong(LR3)"without any other operations for the corresponding animals.Other groups were given corresponding medications.According to different time points,the forced swimming test(FST)was conducted in mice,and the FST and novelty-suppressed feeding test(NSFT)were measured in rats.Monoamine neurotransmitters(NE,DA,DOPAC,5-HT,5-HIAA,HVA)in the prefrontal cortex and hippocampus were detected with high performance liquid chromatography(HPLC).The expression of synapsin I,PSD95,p-mTOR,mTOR,and BDNF in the prefrontal cortex and hippocampus was determined by western blot.Results:At the 1 h time point,compared with the model group,the immobility time was significantly decreased in the acupuncture group(P<0.05).At 3 h,6 h,12 h,and 24 h,compared with the model group,the immobility time was significantly reduced in both scopolamine and acupuncture groups(P<0.05).At the 1 h time point,compared with the normal group,the immobility time of FST and the latency to feed were significantly increased in the model group(P<0.05).Compared with the model group,the immobility time of FST showed a significant reduction in the acupuncture group(P<0.05).At the 6h and 24 h time points,compared with the normal group,the immobility time of FST and the latency to feed were significantly increased in the model group(P<0.05).Compared with the model group,the immobility time of FST was significantly decreased in the scopolamine and acupuncture groups(P<0.05).At the 1 h and 24 h time points,compared with the normal group,the expression levels of 5-HT,5-HIAA,NE,DA,DOPAC,and HVA of the prefrontal cortical and hippocampal tissues were significantly reduced in the model group(P<0.05).At the 1 h and 24 h time points,compared with the model group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the prefrontal cortex were significantly increased in the acupuncture group(P<0.05).At the 1 h and 24 h time points,compared with the normal group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the prefrontal cortex were significantly reduced in the model group(P<0.05).Compared with the model group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the prefrontal cortex were significantly increased in the acupuncture group(P<0.05).At the 1 h and 24 h time points,compared with the normal group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the hippocampal tissues were significantly reduced in the model group(P<0.05).Compared with the model group,the expression levels of synapsin I,PSD95,p-mTOR,and BDNF of the hippocampus were not significantly different in the acupuncture group(P>0.05).Conclusion:Acupuncture may play a rapid antidepressant effect by increasing the expression of synaptic plasticity proteins in the prefrontal cortex.
基金Chinese Postdoctoral Natural Funding,Grant/Award Number:2022M710884Research Foundation of Guangzhou Women and Children's Medical Center,Grant/Award Number:KTa377a204193688National Natural Science Foundation of China,Grant/Award Number:82202251。
文摘Background: Neuroblastoma is one common pediatric malignancy notorious forhigh temporal and spatial heterogeneities. More than half of its patients developdistant metastases involving vascularized organs, especially the bone marrow. It isthus necessary to have an economical, noninvasive method without muchradiation for follow‐ups. Radiomics has been used in many cancers to assistaccurate diagnosis but not yet in bone marrow metastasis in neuroblastoma.Methods: A total of 182 patients with neuroblastoma were retrospectivelycollected and randomly divided into the training and validation sets. Fivehundredand seventy‐two radiomics features were extracted from magneticresonance imaging, among which 41 significant ones were selected via T‐testfor model development. We attempted 13 machine‐learning algorithms andeventually chose three best‐performed models. The integrative performanceevaluations are based on the area under the curves (AUCs), calibration curves,risk deciles plots, and other indexes.Results: Extreme gradient boosting, random forest (RF), and adaptiveboosting were the top three to predict bone marrow metastases in neuroblastoma while RF was the most accurate one. Its AUC was 0.90(0.86–0.93), F1 score was 0.82, sensitivity was 0.76, and negative predictivevalue was 0.79 in the training set. The values were 0.82 (0.71–0.93), 0.80,0.75, and 0.92 in the validation set, respectively.Conclusions: Radiomics models are likely to contribute more to metastaticdiagnoses and the formulation of personalized healthcare strategies in clinics.It has great potential of being a revolutionary method to replace traditionalinterventions in the future.
基金funded by grants from the National Natural Science Foundation of China(No:82003523)the Natural Science Foundation of Guangdong Province(No:2021A1515010860)the Science and Technology Project of Guangzhou(No:202102010170).
文摘To the Editor:Wilms tumor,or nephroblastoma,is the most frequently diagnosed pediatric kidney cancer,accounting for>90%of all renal tumors in children 1–7 years old,and the disease may be related to genetic factors.^([1])As an emerging research spot,the epitranscriptome has been implicated in different RNA modifications in human diseases,including cancers.[2]Methyltransferaselike 1(METTL1),a critical RNA N7-methylguanosine(m7G)methyltransferase,can catalyze the formation of a m7G modification(mostly at nucleotide position 46 in the variable region of transfer RNAs[tRNAs])by complexing with WD repeat domain 4(WDR4).Depending on the different positions,the tRNA m7G modifications have various functions.
基金Chineses Postdoctoral Natural Funding,Grant/Award Number:2022M710884National Natural Science Foundation of China,Grant/Award Number:82202251Research Foundation of Guangzhou Women and Children's Medical Center for Clinical Doctor,Grant/Award Numbers:KTa377a204193688,KT072c1204164651。
文摘Background:It has been observed that cancer and venous thromboembolism(VTE)are associated,but anticancer therapy may violate the causality.Therefore,this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization(MR).Methods:Three MR methods were used to estimate causal effects:Inverse variance weighted(IVW),MR-Egger and weighted median.Sensitivity analyses included Cochran's Q-test,MR-Egger intercept test and MRPRESSO.Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients.Results:The primary IVW approach showed that non-Hodgkin's lymphoma(NHL)might increase the risk of VTE(odds ratio[OR]:1.20,95%confidence interval[95%CI]:1.00–1.44,p=0.045),while melanoma possibly reduced the risk of VTE(OR:0.89,95%CI:0.82–0.97,p=0.006),although there was no significance after adjustment for multiple testing.No association was observed between VTE risk and other site-specific cancers.Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients.Conclusions:Our findings suggested that genetically predicted NHL was associated with higher VTE risk,whereas melanoma had lower VTE risk compared with other site-specific cancers.Moreover,this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.
