Background:Meat quality is largely driven by fat deposition,which is regulated by several genes and signaling pathways.The cyclic adenosine monophosphate(cAMP)-regulated transcriptional coactivator 3(CRTC3)is a coacti...Background:Meat quality is largely driven by fat deposition,which is regulated by several genes and signaling pathways.The cyclic adenosine monophosphate(cAMP)-regulated transcriptional coactivator 3(CRTC3)is a coactivator of cAMP response element binding protein(CREB)that mediates the function of protein kinase A(PKA)signaling pathway and is involved in various biological processes including lipid and energy metabolism.However,the effects of CRTC3 on the metabolome and transcriptome of porcine subcutaneous adipocytes have not been studied yet.Here,we tested whether porcine CRTC3 expression would be related to fat deposition in Heigai pigs(a local fatty breed in China)and Duroc×Landrace×Yorkshire(DLY,a lean breed)pigs in vivo.The effects of adenovirus-induced CRTC3 overexpression on the metabolomic and transcriptomic profiles of subcutaneous adipocytes were also determined in vitro by performing mass spectrometry-based metabolomics combined with RNA sequencing(RNA-seq).Results:Porcine CRTC3 expression is associated with fat deposition in vivo.In addition,CRTC3 overexpression increased lipid accumulation and the expression of mature adipocyte-related genes in cultured porcine subcutaneous adipocytes.According to the metabolomic analysis,CRTC3 overexpression induced significant changes in adipocyte lipid,amino acid and nucleotide metabolites in vitro.The RNA-seq analysis suggested that CRTC3 overexpression alters the expression of genes and pathways involved in adipogenesis,fatty acid metabolism and glycerophospholipid metabolism in vitro.Conclusions:We identified significant alterations in the metabolite composition and the expression of genes and pathways involved in lipid metabolism in CRTC3-overexpressing adipocytes.Our results suggest that CRTC3 might play an important regulatory role in lipid metabolism and thus affects lipid accumulation in porcine subcutaneous adipocytes.展开更多
Objective:Cognitive impairment is a core deficit of schizophrenia and current antipsychotic treatments have no or only very limited effects on cognitive impairment.Clinical studies have found that about 50%~90%of all ...Objective:Cognitive impairment is a core deficit of schizophrenia and current antipsychotic treatments have no or only very limited effects on cognitive impairment.Clinical studies have found that about 50%~90%of all psychiatric patients are smokers,and the high rate of smoking may be due to the fact that the patients smoke tobacco to reduce their cognitive symptoms.Nicotine is the key psychoactive component and various studies have reported that nicotine can improve cognition under some circumstances.Therefore,we propose our hypothesis that nicotine alleviates schizophreniainduced cognitive impairment.Our published results confirmed that nicotine treatment significantly improved rat’s working memory in the delayed alternate T maze task(DAT).Methods:In this current study,MK-801 was applied to induce schizophrenia-like behavior which was confi rmed by pre-pulse inhibition(PPI)and T-maze used to assess cognitive performance.Results:Our data showed that MK-801 caused cognitive impairment accompanied by an increase of Pdlim5,anadaptor protein that is critically associated with schizophrenia in medial prefrontal cortex(mPFC).Of note,chronic nicotine treatment attenuates MK-801-induced schizophrenia-like symptom as well as cognitive impairment by regulating Pdlim5.In addition,nicotine treatment also reduced MK-801-induced decrease of CREBregulated transcription coactivator 1(CRTC1),a coactivator of CREB which has been shown to play an important role in cognition.More important,MK-801 neither induced schizophrenia-like behavior in pdlim5-/-mice,nor decreased CRTC1 in mPFC.Conclusion:Our results showed that chronic nicotine treatment alleviates schizophrenia-induced memory defi cit through regulating Pdlim5 and CRTC1 in mice.展开更多
加拿大的广播和电信管制机构是加拿大无线电广播电视和电信委员会(Canadian Radio-television and Telecommunications Commission)简称CRTC,该机构是加拿大议会根据加拿大无线电广播电视和电信委员会法案(Canadian Radio-television an...加拿大的广播和电信管制机构是加拿大无线电广播电视和电信委员会(Canadian Radio-television and Telecommunications Commission)简称CRTC,该机构是加拿大议会根据加拿大无线电广播电视和电信委员会法案(Canadian Radio-television and Tele-communications Commission Act)建立的公共独立管制机构,通过加拿大遗产部( the Minister of Canadian Heritage. )向议会报告工作.展开更多
BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents not...BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.展开更多
基金The project was partially supported by the National Natural Science Foundation of China(31722053,31672427)the Natural Science Foundation of Zhejiang Province(LR17C170001)the“Hundred Talents Program”funding from Zhejiang University awarded to TZS.
文摘Background:Meat quality is largely driven by fat deposition,which is regulated by several genes and signaling pathways.The cyclic adenosine monophosphate(cAMP)-regulated transcriptional coactivator 3(CRTC3)is a coactivator of cAMP response element binding protein(CREB)that mediates the function of protein kinase A(PKA)signaling pathway and is involved in various biological processes including lipid and energy metabolism.However,the effects of CRTC3 on the metabolome and transcriptome of porcine subcutaneous adipocytes have not been studied yet.Here,we tested whether porcine CRTC3 expression would be related to fat deposition in Heigai pigs(a local fatty breed in China)and Duroc×Landrace×Yorkshire(DLY,a lean breed)pigs in vivo.The effects of adenovirus-induced CRTC3 overexpression on the metabolomic and transcriptomic profiles of subcutaneous adipocytes were also determined in vitro by performing mass spectrometry-based metabolomics combined with RNA sequencing(RNA-seq).Results:Porcine CRTC3 expression is associated with fat deposition in vivo.In addition,CRTC3 overexpression increased lipid accumulation and the expression of mature adipocyte-related genes in cultured porcine subcutaneous adipocytes.According to the metabolomic analysis,CRTC3 overexpression induced significant changes in adipocyte lipid,amino acid and nucleotide metabolites in vitro.The RNA-seq analysis suggested that CRTC3 overexpression alters the expression of genes and pathways involved in adipogenesis,fatty acid metabolism and glycerophospholipid metabolism in vitro.Conclusions:We identified significant alterations in the metabolite composition and the expression of genes and pathways involved in lipid metabolism in CRTC3-overexpressing adipocytes.Our results suggest that CRTC3 might play an important regulatory role in lipid metabolism and thus affects lipid accumulation in porcine subcutaneous adipocytes.
文摘Objective:Cognitive impairment is a core deficit of schizophrenia and current antipsychotic treatments have no or only very limited effects on cognitive impairment.Clinical studies have found that about 50%~90%of all psychiatric patients are smokers,and the high rate of smoking may be due to the fact that the patients smoke tobacco to reduce their cognitive symptoms.Nicotine is the key psychoactive component and various studies have reported that nicotine can improve cognition under some circumstances.Therefore,we propose our hypothesis that nicotine alleviates schizophreniainduced cognitive impairment.Our published results confirmed that nicotine treatment significantly improved rat’s working memory in the delayed alternate T maze task(DAT).Methods:In this current study,MK-801 was applied to induce schizophrenia-like behavior which was confi rmed by pre-pulse inhibition(PPI)and T-maze used to assess cognitive performance.Results:Our data showed that MK-801 caused cognitive impairment accompanied by an increase of Pdlim5,anadaptor protein that is critically associated with schizophrenia in medial prefrontal cortex(mPFC).Of note,chronic nicotine treatment attenuates MK-801-induced schizophrenia-like symptom as well as cognitive impairment by regulating Pdlim5.In addition,nicotine treatment also reduced MK-801-induced decrease of CREBregulated transcription coactivator 1(CRTC1),a coactivator of CREB which has been shown to play an important role in cognition.More important,MK-801 neither induced schizophrenia-like behavior in pdlim5-/-mice,nor decreased CRTC1 in mPFC.Conclusion:Our results showed that chronic nicotine treatment alleviates schizophrenia-induced memory defi cit through regulating Pdlim5 and CRTC1 in mice.
文摘加拿大的广播和电信管制机构是加拿大无线电广播电视和电信委员会(Canadian Radio-television and Telecommunications Commission)简称CRTC,该机构是加拿大议会根据加拿大无线电广播电视和电信委员会法案(Canadian Radio-television and Tele-communications Commission Act)建立的公共独立管制机构,通过加拿大遗产部( the Minister of Canadian Heritage. )向议会报告工作.
基金Hunan Provincial Natural Science Foundation of China,No.2022JJ40246The Hunan Cancer Hospital Climb Plan,No.2021NSFC-B005.
文摘BACKGROUND Pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignancy that arises from minor salivary glands within the tracheobronchial tree.The clear cell variant of PMEC is exceptionally uncommon and presents notable diagnostic challenges,primarily attributable to its morphological similarity to other tumors containing clear cells.CASE SUMMARY A 22-year-old male,formerly in good health,came in with a two-month duration of persistent cough and production of sputum.Subsequent imaging and bronchoscopy examinations revealed a 2 cm tumor in the distal left main bronchus,which resulted in complete atelectasis of the left lung.Further assessment via positron emission tomography/computed tomography scans and endoscopic biopsy confirmed the primary malignant nature of the tumor,charac-terized by clear cell morphology in most of the tumor cells.The patient underwent a left lower lobe sleeve resection accompanied by systematic mediastinal lymph node dissection.Molecular pathology analysis subsequently revealed a CRTC3-MAML2 gene fusion,leading to a definitive pathological diagnosis of the clear cell variant of PMEC,staged as T2N0M0.After surgery,the patient experienced a smooth recovery and exhibited no signs of recurrence during the one-and-a-half-year follow-up period.CONCLUSION This article describes an unusual case of a clear cell variant of PMEC characterized by the presence of a CRTC3-MAML2 gene fusion in a 22-year-old male.The patient underwent successful left lower lobe sleeve resection.This case underscores the distinctive challenges associated with diagnosing and treating this uncommon malignancy,underscoring the importance of precise diagnosis and personalized treatment strategies.
