BACKGROUND Kommerell’s diverticulum(KD)with aberrant left subclavian artery is a rare congenital deformity and also has very little research literature about it(35%of case study).There are three types of aortic arch ...BACKGROUND Kommerell’s diverticulum(KD)with aberrant left subclavian artery is a rare congenital deformity and also has very little research literature about it(35%of case study).There are three types of aortic arch diverticulum.Even literature concerning the treatment options are limited.CASE SUMMARY We present a case report of a 50-year-old male with KD in the right aortic arch with aberrant left subclavian artery.We conducted a total endovascular repair procedure,which is innovative and will spread more light in the medical world.Our patient has no past medical history and is a non-smoker and non-alcoholic.Patient presented with shortness of breath,chest pain and dizziness for six months.Blood tests were done and computerized tomography(CT)angiogram of the chest confirmed the diagnosis,illustrating showed a 3.9 cm KD.On Day 1,the CT angiogram showed mild dilatation of the thoracic aorta,adjacent esophagus,trachea was compressed and displaced.Surgery was planned as the treatment modality.Carotid-Subclavian artery bypass and endovascular aortic repair was conducted.We used prolene 5-0 C1 sutures to precisely anastomose a 6-mm Dacron graft to the left subclavian artery.Haemostasis was secured and wounds were closed.Protamine was administered and patient was shifted to intensive care unit.Post-operative,patient responded favorably and was discharged.Regular follow-up is done.CONCLUSION The procedure we performed is novel.This will help the cardio-thoracic surgeons a better insight about the full procedures we conducted,thereby bringing more light and better treatment options in managing KD with aberrant subclavian artery.展开更多
AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investiga...AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway. TGF-β_1, TβRⅠ, TβRⅡ, Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-β_1, Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-β_1, TβRⅠ , TβRⅡ , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, signifi cantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P < 0.05). The positiveexpression ratio of Smad7 in cases with benign biliary stricture was 70.0%, higher than that in normal bile duct, but this difference is not statistically signifi cant 70.0% vs 50%, P > 0.05). There was a positive correlation between positive expression of TGF-β_1, Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-β/Smad/ CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.展开更多
Objective:To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the antiangiogenesis therapy.Methods:The siRNA tech...Objective:To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the antiangiogenesis therapy.Methods:The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor(VEGF) in A549 cells and simulate the clinical course of anti-angiogencsis therapy.Real-time PCR and western-blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively,as well as the effect on the epithelial mesenchymal transition in A549 cells.The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy.Results:The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy.Under the action of 50 nM VEGF siRNA,the proliferation ability of A549 significantly increased(P<0.05).After being treated with VEGF siRNA,the invasion ability of cells increased.Twenty-four hours after the transcription of 50 nM siRNA into cells,the number of cells that come through the membrane was278.3 ± 12.9.Compared with the Ctrl siRNA group,when VEGF was inhibited,the expression ofβ-catenin and Cyclin D1 increased by 86%and 55%respectively.Meanwhile,the expression of E-cadherin decreased,while the one of vimentin increased.Conclusions:siRNA can significantly inhibit the expression of VEGF.For the anti-angiogencsis therapy,the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.展开更多
The selective hyperpolarization-activated cyclic nucleotide-gated(HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride(ZD7288) blocks the induction of long-term pot...The selective hyperpolarization-activated cyclic nucleotide-gated(HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride(ZD7288) blocks the induction of long-term potentiation in the perforant path-CA3 region in rat hippocampus in vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path-CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hippocampal neurons using high performance liquid chromatography, and determined intracellular Ca2+ concentration([Ca2+]i) using Fura-2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspecific HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Furthermore, ZD7288 attenuated glutamate-induced rises in [Ca2+]i in a concentration-dependent manner and reversed 8-Br-c AMP-mediated facilitation of these glutamate-induced [Ca2+]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both glutamate release and resultant [Ca2+]i increases in rat hippocampal neurons.展开更多
Limestone(CaCO3),which could promote sulfur fixation,was added to coal gangue during roasting in a circulating fluidized bed(CFB)boiler.CaO and CaSO_(4) were the main Ca-bearing minerals while metakaolinite was the ma...Limestone(CaCO3),which could promote sulfur fixation,was added to coal gangue during roasting in a circulating fluidized bed(CFB)boiler.CaO and CaSO_(4) were the main Ca-bearing minerals while metakaolinite was the major Al-bearing mineral in CFB slag.The effect of CaSO_(4) and CaO on the separation of alumina and silica from metakaolinite by reduction roasting−alkaline leaching process was studied.Results showed that metakaolinite was completely converted into hercynite and silica solid solutions(i.e.,quartz and cristobalite solid solutions)by reduction roasting with hematite.More than 95%of silica in the reduced specimen was removed by alkaline leaching.The addition of CaSO_(4) and CaO remarkably decreased the separation efficiency of alumina and silica in metakaolinite,which could be attributed to the formation of Si-bearing minerals:(1)Fayalite and anorthite were formed during the reduction roasting process;(2)Fayalite was stable while anorthite was converted into sodalite and wollastonite during the alkaline leaching process.This study demonstrates that sulfur in coal gangue should be fixed by treating the exhaust gas instead of controlling the combustion process of CFB to achieve the comprehensive recovery of silica and alumina from the CFB slag.展开更多
The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying pheno...The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds,African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group,while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function.Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation,energy metabolism, and growth development.Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30domesticated sheep breeds. The IFI44 c. 54413058C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recogn...BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.展开更多
In the central nervous system,hyperpolarizationactivated cyclic nucleotide-gated(HCN)channels are essential to maintain normal neuronal function.Recent studies have shown that HCN channels may be involved in the patho...In the central nervous system,hyperpolarizationactivated cyclic nucleotide-gated(HCN)channels are essential to maintain normal neuronal function.Recent studies have shown that HCN channels may be involved in the pathological process of ischemic brain injury,but the mechanisms remain unclear.Autophagy is activated in cerebral ischemia,but its role in cell death/survival remains controversial.In this study,our results showed that the HCN channel blocker ZD7288 remarkably decreased the percentage of apoptotic neurons and corrected the excessive autophagy induced by oxygen-glucose deprivation followed by reperfusion(OGD/R)in hippocampal HT22 neurons.Furthermore,in the OGD/R group,p-mTOR,p-ULK1(Ser757),and p62 were significantly decreased,while p-ULK1(Ser317),atg5,and beclin1 were remarkably increased.ZD7288 did not change the expression of p-ULK1(Ser757),ULK1(Ser317),p62,Beclin1,and atg5,which are involved in regulating autophagosome formation.Besides,we found that OGD/R induced a significant increase in Cathepsin D expression,but not LAMP-1.Treatment with ZD7288 at 10μmol/L in the OGD/R group did not change the expression of cathepsin D and LAMP-1.However,chloroquine(CQ),which decreases autophagosome-lysosome fusion,eliminated the correction of excessive autophagy and neuroprotection by ZD7288.Besides,shRNA knockdown of HCN2 channels significantly reduced the accumulation of LC3-Ⅱand increased neuron survival in the OGD/R and transient global cerebral ischemia(TGCI)models,and CQ also eliminated the effects of HCN2-shRNA.Furthermore,we found that the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes decreased in Con-shRNAtransfected HT22 neurons exposed to OGD/R or CQ.In HCN2-shRNA-transfected HT22 neurons,the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes increased under OGD/R;however,the percentage was significantly decreased by the addition of CQ to HCN2-shRNA-transfected HT22 neurons.The present results demonstrated that blockade of HCN2 channels provides neuroprotection against OGD/R and TGCI by accelerating autophagic degradation attributable to the promotion of autophagosome and lysosome fusion.展开更多
The solar X-ray and Extreme Ultraviolet Imager(X-EUVI),developed by the Changchun Institute of Optics,Fine Mechanics and Physics,Chinese Academy of Sciences(CIOMP),is the first space-based solar X-ray and Extreme ultr...The solar X-ray and Extreme Ultraviolet Imager(X-EUVI),developed by the Changchun Institute of Optics,Fine Mechanics and Physics,Chinese Academy of Sciences(CIOMP),is the first space-based solar X-ray and Extreme ultraviolet(EUV)imager of China loaded on the Fengyun-3E(FY-3E)satellite supported by the China Meteorological Administration(CMA)for solar observation.Since started work on July 11,2021,X-EUVI has obtained many solar images.The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun,which covers 0.6-8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region.X-EUVI has a field of view of 42′,an angular resolution of 2.5″per pixel in the EUV band and an angular resolution of 4.1″per pixel in the X-ray band.The instrument also includes an X-ray and EUV irradiance sensor(X-EUVS)with the same bands as its imaging optics,which measures the solar irradiance and regularly calibrates the solar images.The radiometric calibration of X-EUVS on the ground has been completed,with a calibration accuracy of 12%.X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate.Flat-field calibration is conducted by utilizing successive rotation solar images.The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.展开更多
文摘BACKGROUND Kommerell’s diverticulum(KD)with aberrant left subclavian artery is a rare congenital deformity and also has very little research literature about it(35%of case study).There are three types of aortic arch diverticulum.Even literature concerning the treatment options are limited.CASE SUMMARY We present a case report of a 50-year-old male with KD in the right aortic arch with aberrant left subclavian artery.We conducted a total endovascular repair procedure,which is innovative and will spread more light in the medical world.Our patient has no past medical history and is a non-smoker and non-alcoholic.Patient presented with shortness of breath,chest pain and dizziness for six months.Blood tests were done and computerized tomography(CT)angiogram of the chest confirmed the diagnosis,illustrating showed a 3.9 cm KD.On Day 1,the CT angiogram showed mild dilatation of the thoracic aorta,adjacent esophagus,trachea was compressed and displaced.Surgery was planned as the treatment modality.Carotid-Subclavian artery bypass and endovascular aortic repair was conducted.We used prolene 5-0 C1 sutures to precisely anastomose a 6-mm Dacron graft to the left subclavian artery.Haemostasis was secured and wounds were closed.Protamine was administered and patient was shifted to intensive care unit.Post-operative,patient responded favorably and was discharged.Regular follow-up is done.CONCLUSION The procedure we performed is novel.This will help the cardio-thoracic surgeons a better insight about the full procedures we conducted,thereby bringing more light and better treatment options in managing KD with aberrant subclavian artery.
基金The grant from Shaanxi Science and Technology Project, No. 2002K10-G8
文摘AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway. TGF-β_1, TβRⅠ, TβRⅡ, Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-β_1, Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-β_1, TβRⅠ , TβRⅡ , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, signifi cantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P < 0.05). The positiveexpression ratio of Smad7 in cases with benign biliary stricture was 70.0%, higher than that in normal bile duct, but this difference is not statistically signifi cant 70.0% vs 50%, P > 0.05). There was a positive correlation between positive expression of TGF-β_1, Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-β/Smad/ CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.
基金supported by National Natural Science Foundation(No.81372530)
文摘Objective:To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the antiangiogenesis therapy.Methods:The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor(VEGF) in A549 cells and simulate the clinical course of anti-angiogencsis therapy.Real-time PCR and western-blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively,as well as the effect on the epithelial mesenchymal transition in A549 cells.The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy.Results:The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy.Under the action of 50 nM VEGF siRNA,the proliferation ability of A549 significantly increased(P<0.05).After being treated with VEGF siRNA,the invasion ability of cells increased.Twenty-four hours after the transcription of 50 nM siRNA into cells,the number of cells that come through the membrane was278.3 ± 12.9.Compared with the Ctrl siRNA group,when VEGF was inhibited,the expression ofβ-catenin and Cyclin D1 increased by 86%and 55%respectively.Meanwhile,the expression of E-cadherin decreased,while the one of vimentin increased.Conclusions:siRNA can significantly inhibit the expression of VEGF.For the anti-angiogencsis therapy,the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.
基金supported by grants from the National Natural Science Foundation of China,No.81173038,81001425
文摘The selective hyperpolarization-activated cyclic nucleotide-gated(HCN) channel blocker 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride(ZD7288) blocks the induction of long-term potentiation in the perforant path-CA3 region in rat hippocampus in vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path-CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hippocampal neurons using high performance liquid chromatography, and determined intracellular Ca2+ concentration([Ca2+]i) using Fura-2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspecific HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Furthermore, ZD7288 attenuated glutamate-induced rises in [Ca2+]i in a concentration-dependent manner and reversed 8-Br-c AMP-mediated facilitation of these glutamate-induced [Ca2+]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both glutamate release and resultant [Ca2+]i increases in rat hippocampal neurons.
基金the financial supports from the National Natural Science Foundation of China (Nos. 52004194, 51874219)the China Postdoctoral Science Foundation (No. 2019M662733)。
文摘Limestone(CaCO3),which could promote sulfur fixation,was added to coal gangue during roasting in a circulating fluidized bed(CFB)boiler.CaO and CaSO_(4) were the main Ca-bearing minerals while metakaolinite was the major Al-bearing mineral in CFB slag.The effect of CaSO_(4) and CaO on the separation of alumina and silica from metakaolinite by reduction roasting−alkaline leaching process was studied.Results showed that metakaolinite was completely converted into hercynite and silica solid solutions(i.e.,quartz and cristobalite solid solutions)by reduction roasting with hematite.More than 95%of silica in the reduced specimen was removed by alkaline leaching.The addition of CaSO_(4) and CaO remarkably decreased the separation efficiency of alumina and silica in metakaolinite,which could be attributed to the formation of Si-bearing minerals:(1)Fayalite and anorthite were formed during the reduction roasting process;(2)Fayalite was stable while anorthite was converted into sodalite and wollastonite during the alkaline leaching process.This study demonstrates that sulfur in coal gangue should be fixed by treating the exhaust gas instead of controlling the combustion process of CFB to achieve the comprehensive recovery of silica and alumina from the CFB slag.
基金supported by the National Key R&D Program of China (2021YFD1300901)National Natural Science Foundation of China (31960653)+1 种基金West Light Foundation of the Chinese Academy of SciencesNational Joint Research on Improved Breeds of Livestock and Poultry (19210365)。
文摘The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds,African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group,while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function.Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation,energy metabolism, and growth development.Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30domesticated sheep breeds. The IFI44 c. 54413058C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.
基金Supported by National Natural Science Foundation of China,No.82172944 and No.81900558Co-operation Research Plan of Medical Science and Technology of Henan Province,No.LHGJ20190149the Key Scientific Research Projects of Universities of Henan Province,No.21A320052。
文摘BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.
基金supported by grants from the National Natural Science Foundation of China (85100929)the Natural Science Foundation of Hubei Province,China (2018CFB302 and 2019CFB446)the Youth Fund of Health and Family Planning Commission of Wuhan Municipality,Hubei Province,China (WX18Q13 and WX18Q22)。
文摘In the central nervous system,hyperpolarizationactivated cyclic nucleotide-gated(HCN)channels are essential to maintain normal neuronal function.Recent studies have shown that HCN channels may be involved in the pathological process of ischemic brain injury,but the mechanisms remain unclear.Autophagy is activated in cerebral ischemia,but its role in cell death/survival remains controversial.In this study,our results showed that the HCN channel blocker ZD7288 remarkably decreased the percentage of apoptotic neurons and corrected the excessive autophagy induced by oxygen-glucose deprivation followed by reperfusion(OGD/R)in hippocampal HT22 neurons.Furthermore,in the OGD/R group,p-mTOR,p-ULK1(Ser757),and p62 were significantly decreased,while p-ULK1(Ser317),atg5,and beclin1 were remarkably increased.ZD7288 did not change the expression of p-ULK1(Ser757),ULK1(Ser317),p62,Beclin1,and atg5,which are involved in regulating autophagosome formation.Besides,we found that OGD/R induced a significant increase in Cathepsin D expression,but not LAMP-1.Treatment with ZD7288 at 10μmol/L in the OGD/R group did not change the expression of cathepsin D and LAMP-1.However,chloroquine(CQ),which decreases autophagosome-lysosome fusion,eliminated the correction of excessive autophagy and neuroprotection by ZD7288.Besides,shRNA knockdown of HCN2 channels significantly reduced the accumulation of LC3-Ⅱand increased neuron survival in the OGD/R and transient global cerebral ischemia(TGCI)models,and CQ also eliminated the effects of HCN2-shRNA.Furthermore,we found that the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes decreased in Con-shRNAtransfected HT22 neurons exposed to OGD/R or CQ.In HCN2-shRNA-transfected HT22 neurons,the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes increased under OGD/R;however,the percentage was significantly decreased by the addition of CQ to HCN2-shRNA-transfected HT22 neurons.The present results demonstrated that blockade of HCN2 channels provides neuroprotection against OGD/R and TGCI by accelerating autophagic degradation attributable to the promotion of autophagosome and lysosome fusion.
基金supported in part by the National Science Foundation of China(Grant Nos.41931073,10878004,U1931118 and 42104166).
文摘The solar X-ray and Extreme Ultraviolet Imager(X-EUVI),developed by the Changchun Institute of Optics,Fine Mechanics and Physics,Chinese Academy of Sciences(CIOMP),is the first space-based solar X-ray and Extreme ultraviolet(EUV)imager of China loaded on the Fengyun-3E(FY-3E)satellite supported by the China Meteorological Administration(CMA)for solar observation.Since started work on July 11,2021,X-EUVI has obtained many solar images.The instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun,which covers 0.6-8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region.X-EUVI has a field of view of 42′,an angular resolution of 2.5″per pixel in the EUV band and an angular resolution of 4.1″per pixel in the X-ray band.The instrument also includes an X-ray and EUV irradiance sensor(X-EUVS)with the same bands as its imaging optics,which measures the solar irradiance and regularly calibrates the solar images.The radiometric calibration of X-EUVS on the ground has been completed,with a calibration accuracy of 12%.X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform rate.Flat-field calibration is conducted by utilizing successive rotation solar images.The agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.