Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from t...Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from the GEO,and the differently expressed analysis were conducted by R software limma package.Functional enrichment analysis was performed using R software.The targets of differently expressed miRNAs were predicted by FunRich software,and the miRNA-mRNA regulatory network was constructed by Cytoscape software.The cMAP and TCMSP databases were used to predict small molecule drugs and traditional Chinese medicine respectively.Results:A total of 79 differently expressed miRNAs and 8865 differently expressed mRNAs were identified.Then the miRNA-mRNA regulatory network was constructed.Among DE miRNAs in the network,hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p may be the most significant due to their large number of connecting nodes in ulcerative colitis associated colorectal cancer.The integrated differently genes were mainly concentrated in protein processing in endoplasmic reticulum,ferroptosis and other signalingpathways.In addition,10 kinds of small molecule drugs and 6 kinds of traditional Chinese medicine were screened as therapeutic agents for ulcerative colitis associated colorectal cancer.Conclusion:hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p can be used as therapeutic targets forulcerative colitis associated colorectal cancer.The pathogenesis of ulcerative colitis associated colorectal cancer may be related to the protein processing in endoplasmic reticulum/ferroptosis signaling pathway,and it is predicted that 10 kinds of small molecule drugs,such asIsoflupredone,and 4 traditional Chinese medicines,such as Baiqucai(Celandine),Guanhuangbai(Cortex phellodendri amurensis),Huangbai(Phellodendron amurense)and Bajiaolian(Dysosma Versipellis),can be used as therapeutic drugs forulcerative colitis associated colorectal cancer.展开更多
We present in situ trace element and Nd isotopic data of apatites from metamorphosed and metasomatized(i.e.,altered)and unaltered granitoids in the Songnen and Jiamusi massifs in the eastern Central Asian Orogenic Bel...We present in situ trace element and Nd isotopic data of apatites from metamorphosed and metasomatized(i.e.,altered)and unaltered granitoids in the Songnen and Jiamusi massifs in the eastern Central Asian Orogenic Belt,with the aim of fingerprinting granitoid petrogenesis,including both the magmatic and post-magmatic evolution processes.Apatites from altered granitoids(AG)and unaltered granitoids(UG)are characterized by distinct textures and geochemical compositions.Apatites from AG have irregular rim overgrowths and complex internal textures,along with low contents of rare earth elements(REEs),suggesting the re-precipitation of apatite during epidote crystallization and/or leaching of REEs from apatite by metasomatic fluids.eNd(t)values of the these apatites are decoupled from zircon eHf(t)values for most samples,which can be attributed to the higher mobility of Nd as compared to Sm in certain fluids.Apatites from UG are of igneous origin based on their homogeneous or concentric zoned textures and coupled Nd-Hf isotopic compositions.Trace element variations in igneous apatite are controlled primarily by the geochemical composition of the parental melt,fractional crystallization of other REEbearing minerals,and changes in partition coefficients.Sr contents and Eu/Eu^(*) values of apatites from UG correlate with whole-rock Sr and SiO2 contents,highlighting the effects of plagioclase fractionation during magma evolution.Apatites from UG can be subdivided into four groups based on REE contents.Group 1 apatites have REE patterns similar to the host granitoids,but are slightly enriched in middle REEs,reflecting the influence of the parental melt composition and REE partitioning.Group 2 apatites exhibit strong light REE depletions,whereas Group 3 apatites are depleted in middle and heavy REEs,indicative of the crystallization of epidote-group minerals and hornblende before and/or during apatite crystallization,respectively.Group 4 apatites are depleted in heavy REEs,but enriched in Sr,which are features of adakites.Some unusual geochemical features of the apatites,including the REE patterns,Sr contents,Eu anomalies,and Nd isotopic compositions,indicate that inherited apatites are likely to retain the geochemical features of their parental magmas,and thus provide a record of small-scale crustal assimilation during magma evolution that is not evident from the whole-rock geochemistry.展开更多
Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke.The narrow treatment time window is still to be solved.Given that the ischemic core expanded ove...Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke.The narrow treatment time window is still to be solved.Given that the ischemic core expanded over days,treatment with an extended time window is anticipated.Bestrophin1(BEST1)belongs to a bestrophin family of calcium-activated chloride channels.We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice.Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits.Using electrophysiological recordings,we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity.Finally,we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6—72 h post-ischemia in rodents.This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions.Our study identifies the glutamatereleasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.展开更多
文摘Objective:To construct the miRNA-mRNA regulatory network,andidentify more reliable therapeutic targets and potential drugs in ulcerative colitis associated colorectal cancer.Methods:Two datasets were downloaded from the GEO,and the differently expressed analysis were conducted by R software limma package.Functional enrichment analysis was performed using R software.The targets of differently expressed miRNAs were predicted by FunRich software,and the miRNA-mRNA regulatory network was constructed by Cytoscape software.The cMAP and TCMSP databases were used to predict small molecule drugs and traditional Chinese medicine respectively.Results:A total of 79 differently expressed miRNAs and 8865 differently expressed mRNAs were identified.Then the miRNA-mRNA regulatory network was constructed.Among DE miRNAs in the network,hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p may be the most significant due to their large number of connecting nodes in ulcerative colitis associated colorectal cancer.The integrated differently genes were mainly concentrated in protein processing in endoplasmic reticulum,ferroptosis and other signalingpathways.In addition,10 kinds of small molecule drugs and 6 kinds of traditional Chinese medicine were screened as therapeutic agents for ulcerative colitis associated colorectal cancer.Conclusion:hsa-miR-520e,hsa-miR-199b-5p,hsa-miR-140-5p can be used as therapeutic targets forulcerative colitis associated colorectal cancer.The pathogenesis of ulcerative colitis associated colorectal cancer may be related to the protein processing in endoplasmic reticulum/ferroptosis signaling pathway,and it is predicted that 10 kinds of small molecule drugs,such asIsoflupredone,and 4 traditional Chinese medicines,such as Baiqucai(Celandine),Guanhuangbai(Cortex phellodendri amurensis),Huangbai(Phellodendron amurense)and Bajiaolian(Dysosma Versipellis),can be used as therapeutic drugs forulcerative colitis associated colorectal cancer.
基金supported by the National Natural Science Foundation of China(grant numbers 42072071,41772047).
文摘We present in situ trace element and Nd isotopic data of apatites from metamorphosed and metasomatized(i.e.,altered)and unaltered granitoids in the Songnen and Jiamusi massifs in the eastern Central Asian Orogenic Belt,with the aim of fingerprinting granitoid petrogenesis,including both the magmatic and post-magmatic evolution processes.Apatites from altered granitoids(AG)and unaltered granitoids(UG)are characterized by distinct textures and geochemical compositions.Apatites from AG have irregular rim overgrowths and complex internal textures,along with low contents of rare earth elements(REEs),suggesting the re-precipitation of apatite during epidote crystallization and/or leaching of REEs from apatite by metasomatic fluids.eNd(t)values of the these apatites are decoupled from zircon eHf(t)values for most samples,which can be attributed to the higher mobility of Nd as compared to Sm in certain fluids.Apatites from UG are of igneous origin based on their homogeneous or concentric zoned textures and coupled Nd-Hf isotopic compositions.Trace element variations in igneous apatite are controlled primarily by the geochemical composition of the parental melt,fractional crystallization of other REEbearing minerals,and changes in partition coefficients.Sr contents and Eu/Eu^(*) values of apatites from UG correlate with whole-rock Sr and SiO2 contents,highlighting the effects of plagioclase fractionation during magma evolution.Apatites from UG can be subdivided into four groups based on REE contents.Group 1 apatites have REE patterns similar to the host granitoids,but are slightly enriched in middle REEs,reflecting the influence of the parental melt composition and REE partitioning.Group 2 apatites exhibit strong light REE depletions,whereas Group 3 apatites are depleted in middle and heavy REEs,indicative of the crystallization of epidote-group minerals and hornblende before and/or during apatite crystallization,respectively.Group 4 apatites are depleted in heavy REEs,but enriched in Sr,which are features of adakites.Some unusual geochemical features of the apatites,including the REE patterns,Sr contents,Eu anomalies,and Nd isotopic compositions,indicate that inherited apatites are likely to retain the geochemical features of their parental magmas,and thus provide a record of small-scale crustal assimilation during magma evolution that is not evident from the whole-rock geochemistry.
基金supported by STI2030-Major Project(2022ZD0211700,China)National Natural Science Foundation of China(82171293,82090042 and 82171368)Natural Science Foundation of Jiangsu Province(BK20211255,China)。
文摘Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke.The narrow treatment time window is still to be solved.Given that the ischemic core expanded over days,treatment with an extended time window is anticipated.Bestrophin1(BEST1)belongs to a bestrophin family of calcium-activated chloride channels.We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48 h after ischemic stroke in mice.Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits.Using electrophysiological recordings,we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity.Finally,we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6—72 h post-ischemia in rodents.This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions.Our study identifies the glutamatereleasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.