The pore structures and controlling factors of several different Paleozoic shales from Southern China and their kerogens were studied using nitrogen adsorption and scanning electron microscopy methods. The results ind...The pore structures and controlling factors of several different Paleozoic shales from Southern China and their kerogens were studied using nitrogen adsorption and scanning electron microscopy methods. The results indicate that： 1） The specific surface area is 2.22-3.52 m2/g and has no correlation with the TOC content of the Permian Dalong Formation shales, nanopores are extremely undeveloped in the Dalong Formation kerogens, which have specific surface areas of 20.35-27.49 me/g; 2） the specific surface area of the Silurian Longmaxi Formation shales is in the range of 17.83-29.49 m2/g and is positively correlated with TOC content, the kerogens from the Longmaxi Formation have well-developed nanopores, with round or elliptical shapes, and the specific surface areas of these kerogens are as high as 279.84-300.3 m2/g; 3） for the Niutitang Formation shales, the specific surface area is 20.12-29.49 m2/grock and increases significantly with increasing TOC and smectite content. The Niuti- tang Formation kerogens develop a certain amount of nanopores with a specific surface area of 161.2 m2/g. Oil shale was also examined for comparison, and was found to have a specific surface area of 19.99 m2/g. Nanopores are rare in the Youganwo Formation kerogen, which has a specific surface area of only 5.54 m2/g, suggesting that the specific surface area of oil shale is due mainly to the presence of smectite and other clay minerals. The specific surface area and the number of pores present in shales are closely related to TOC, kerogen type and maturity, smectite content, and other factors. Low-maturity kerogen has very few nanopores and therefore has a very low specific surface area, whereas nanopores are abundant in mature to over- mature kerogen, leading to high specific surface areas. The Longmaxi Formation kerogen has more developed nanopores and a higher specific surface area than the Niutitang Formation kerogen, which may be due to differences in the kerogen type and maceral components. A high content of smectite may a展开更多
TANK-binding kinase 1(TBK1)is an essential protein kinase for activation of interferon regulatory factor 3(IRF3)and induction of the type I interferons(IFN-I).Although the biochemical regulation of TBK1 activation has...TANK-binding kinase 1(TBK1)is an essential protein kinase for activation of interferon regulatory factor 3(IRF3)and induction of the type I interferons(IFN-I).Although the biochemical regulation of TBK1 activation has been studied,little is known about how enterovirus 71(EV71)employs the deubiquitinases(DUBs)to regulate TBK1 activation for viral immune evasion.Here,we found that EV71 infection upregulated the expression of ubiquitinspecific protease 24(USP24).Further studies revealed that USP24 physically interacted with TBK1,and can reduce K63-linked polyubiquitination of TBK1.Knockdown of USP24 upregulated TBK1 K63-linked polyubiquitination,promoted the phosphorylation and nuclear translocation of IRF3,and in turn improved IFN-I production during EV71 infection.As a consequence,USP24 knockdown dramatically inhibited EV71 infection.This study revealed USP24 as a novel regulator of TBK1 activation,which promotes the understanding of immune evasion mechanisms of EV71 and could provide a potential strategy for treatment of EV71 infection.展开更多
It is of profound theoretical and practical significance to study endangerment status of rare species in Tibet. Index system is firstly set down for quantitative assessment of rare animal and plant species, then endan...It is of profound theoretical and practical significance to study endangerment status of rare species in Tibet. Index system is firstly set down for quantitative assessment of rare animal and plant species, then endangerment degree of wildlife under special state protection are calculated, which is expressed by value E. The results reveal that Yunnan snub-nosed monkey （Rhinopithecus bieti）, Himalayan tahr （Hemitragus jemlahicus） and Gigantic Cypress （Cupressus gigantea） have the highest E respectively in animals and plants. According to value E, all species are categorized into 4 ranks： critically endangered（0.6-0.8）, endangered （0.4- 0.6）, vulnerable （0.2-0.4） and lower risk （ E ≤ 0.2）. By comparison of the first five animals and plants of the highest E, each sub-ecozone bears a distinct identity.展开更多
Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual ...Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual curation,which is cumbersome and subjective.The increasing number of scRNA-seq datasets,as well as numerous published genetic studies,has motivated us to build a comprehensive human cell type reference atlas.Here,we present decoding Cell type Specificity(deCS),an automatic cell type annotation method augmented by a comprehensive collection of human cell type expression profiles and marker genes.We used deCS to annotate scRNAseq data from various tissue types and systematically evaluated the annotation accuracy under different conditions,including reference panels,sequencing depth,and feature selection strategies.Our results demonstrate that expanding the references is critical for improving annotation accuracy.Compared to many existing state-of-the-art annotation tools,deCS significantly reduced computation time and increased accuracy.deCS can be integrated into the standard scRNA-seq analytical pipeline to enhance cell type annotation.Finally,we demonstrated the broad utility of deCS to identify trait-cell type associations in 51 human complex traits,providing deep insights into the cellular mechanisms underlying disease pathogenesis.展开更多
Objective Ubiquitin-specific protease 4(USP4)facilitates the development of transforming growth factor-beta 1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)in various cancer cells.Moreover,EMT of renal tubula...Objective Ubiquitin-specific protease 4(USP4)facilitates the development of transforming growth factor-beta 1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)in various cancer cells.Moreover,EMT of renal tubular epithelial cells(RTECs)is required for the progression of renal interstitial fibrosis.However,the role of USP4 in EMT of RTECs remains unknown.The present study aimed to explore the effect of USP4 on the EMT of RTECs as well as the involved mechanism.Methods In established unilateral ureteral obstruction(UUO)rats and NRK-52E cells,immunohistochemistry and Western blot assays were performed.Results USP4 expression was increased significantly with obstruction time.In NRK-52E cells stimulated by TGF-β1,USP4 expression was increased in a time-dependent manner.In addition,USP4 silencing with specific siRNA indicated that USP4 protein was suppressed effectively.Meanwhile,USP4 siRNA treatment restored E-cadherin and weakened alpha smooth muscle actin(α-SMA)expression,indicating that USP4 may promote EMT.After treatment with USP4 siRNA and TGF-β1 for 24 h,the expression of TGF-β1 receptor type I(TβRI)was decreased.Conclusion USP4 promotes the EMT of RTECs through upregulating TβRI,thereby facilitating renal interstitial fibrosis.These findings may provide a potential target of USP4 in the treatment of renal fibrosis.展开更多
AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a sy...AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.展开更多
With the increasing of data size and model size,deep neural networks(DNNs)show outstanding performance in many artificial intelligence(AI)applications.But the big model size makes it a challenge for high-performance a...With the increasing of data size and model size,deep neural networks(DNNs)show outstanding performance in many artificial intelligence(AI)applications.But the big model size makes it a challenge for high-performance and low-power running DNN on processors,such as central processing unit(CPU),graphics processing unit(GPU),and tensor processing unit(TPU).This paper proposes a LOGNN data representation of 8 bits and a hardware and software co-design deep neural network accelerator LACC to meet the challenge.LOGNN data representation replaces multiply operations to add and shift operations in running DNN.LACC accelerator achieves higher efficiency than the state-of-the-art DNN accelerators by domain specific arithmetic computing units.Finally,LACC speeds up the performance per watt by 1.5 times,compared to the state-of-the-art DNN accelerators on average.展开更多
基金supported by National Basic Research Program of China(Grant No.2012CB214704)Major National Science and Techno-logy Project(Grant No.2011ZX05008-002-20)National Natural Science Foundation of China(Grant No.4123058)
文摘The pore structures and controlling factors of several different Paleozoic shales from Southern China and their kerogens were studied using nitrogen adsorption and scanning electron microscopy methods. The results indicate that： 1） The specific surface area is 2.22-3.52 m2/g and has no correlation with the TOC content of the Permian Dalong Formation shales, nanopores are extremely undeveloped in the Dalong Formation kerogens, which have specific surface areas of 20.35-27.49 me/g; 2） the specific surface area of the Silurian Longmaxi Formation shales is in the range of 17.83-29.49 m2/g and is positively correlated with TOC content, the kerogens from the Longmaxi Formation have well-developed nanopores, with round or elliptical shapes, and the specific surface areas of these kerogens are as high as 279.84-300.3 m2/g; 3） for the Niutitang Formation shales, the specific surface area is 20.12-29.49 m2/grock and increases significantly with increasing TOC and smectite content. The Niuti- tang Formation kerogens develop a certain amount of nanopores with a specific surface area of 161.2 m2/g. Oil shale was also examined for comparison, and was found to have a specific surface area of 19.99 m2/g. Nanopores are rare in the Youganwo Formation kerogen, which has a specific surface area of only 5.54 m2/g, suggesting that the specific surface area of oil shale is due mainly to the presence of smectite and other clay minerals. The specific surface area and the number of pores present in shales are closely related to TOC, kerogen type and maturity, smectite content, and other factors. Low-maturity kerogen has very few nanopores and therefore has a very low specific surface area, whereas nanopores are abundant in mature to over- mature kerogen, leading to high specific surface areas. The Longmaxi Formation kerogen has more developed nanopores and a higher specific surface area than the Niutitang Formation kerogen, which may be due to differences in the kerogen type and maceral components. A high content of smectite may a
基金support was provided by the National Natural Science Foundation of China(81572052 and 82102473)Changzhou science and technology support plan(CE20225036,CJ20210141)Young Talent Development Plan of Changzhou Health Commission(2020-233).
文摘TANK-binding kinase 1(TBK1)is an essential protein kinase for activation of interferon regulatory factor 3(IRF3)and induction of the type I interferons(IFN-I).Although the biochemical regulation of TBK1 activation has been studied,little is known about how enterovirus 71(EV71)employs the deubiquitinases(DUBs)to regulate TBK1 activation for viral immune evasion.Here,we found that EV71 infection upregulated the expression of ubiquitinspecific protease 24(USP24).Further studies revealed that USP24 physically interacted with TBK1,and can reduce K63-linked polyubiquitination of TBK1.Knockdown of USP24 upregulated TBK1 K63-linked polyubiquitination,promoted the phosphorylation and nuclear translocation of IRF3,and in turn improved IFN-I production during EV71 infection.As a consequence,USP24 knockdown dramatically inhibited EV71 infection.This study revealed USP24 as a novel regulator of TBK1 activation,which promotes the understanding of immune evasion mechanisms of EV71 and could provide a potential strategy for treatment of EV71 infection.
基金the National Natural Science Foundation of China (50099620)
文摘It is of profound theoretical and practical significance to study endangerment status of rare species in Tibet. Index system is firstly set down for quantitative assessment of rare animal and plant species, then endangerment degree of wildlife under special state protection are calculated, which is expressed by value E. The results reveal that Yunnan snub-nosed monkey （Rhinopithecus bieti）, Himalayan tahr （Hemitragus jemlahicus） and Gigantic Cypress （Cupressus gigantea） have the highest E respectively in animals and plants. According to value E, all species are categorized into 4 ranks： critically endangered（0.6-0.8）, endangered （0.4- 0.6）, vulnerable （0.2-0.4） and lower risk （ E ≤ 0.2）. By comparison of the first five animals and plants of the highest E, each sub-ecozone bears a distinct identity.
基金supported by National Institutes of Health grants(Grant Nos.R01LM012806R,I01DE030122,and R01DE029818)support from Cancer Prevention and Research Institute of Texas(Grant Nos.CPRIT RP180734 and RP210045),United States.
文摘Single-cell RNA sequencing(scRNA-seq)is revolutionizing the study of complex and dynamic cellular mechanisms.However,cell type annotation remains a main challenge as it largely relies on a priori knowledge and manual curation,which is cumbersome and subjective.The increasing number of scRNA-seq datasets,as well as numerous published genetic studies,has motivated us to build a comprehensive human cell type reference atlas.Here,we present decoding Cell type Specificity(deCS),an automatic cell type annotation method augmented by a comprehensive collection of human cell type expression profiles and marker genes.We used deCS to annotate scRNAseq data from various tissue types and systematically evaluated the annotation accuracy under different conditions,including reference panels,sequencing depth,and feature selection strategies.Our results demonstrate that expanding the references is critical for improving annotation accuracy.Compared to many existing state-of-the-art annotation tools,deCS significantly reduced computation time and increased accuracy.deCS can be integrated into the standard scRNA-seq analytical pipeline to enhance cell type annotation.Finally,we demonstrated the broad utility of deCS to identify trait-cell type associations in 51 human complex traits,providing deep insights into the cellular mechanisms underlying disease pathogenesis.
文摘Objective Ubiquitin-specific protease 4(USP4)facilitates the development of transforming growth factor-beta 1(TGF-β1)-induced epithelial-mesenchymal transition(EMT)in various cancer cells.Moreover,EMT of renal tubular epithelial cells(RTECs)is required for the progression of renal interstitial fibrosis.However,the role of USP4 in EMT of RTECs remains unknown.The present study aimed to explore the effect of USP4 on the EMT of RTECs as well as the involved mechanism.Methods In established unilateral ureteral obstruction(UUO)rats and NRK-52E cells,immunohistochemistry and Western blot assays were performed.Results USP4 expression was increased significantly with obstruction time.In NRK-52E cells stimulated by TGF-β1,USP4 expression was increased in a time-dependent manner.In addition,USP4 silencing with specific siRNA indicated that USP4 protein was suppressed effectively.Meanwhile,USP4 siRNA treatment restored E-cadherin and weakened alpha smooth muscle actin(α-SMA)expression,indicating that USP4 may promote EMT.After treatment with USP4 siRNA and TGF-β1 for 24 h,the expression of TGF-β1 receptor type I(TβRI)was decreased.Conclusion USP4 promotes the EMT of RTECs through upregulating TβRI,thereby facilitating renal interstitial fibrosis.These findings may provide a potential target of USP4 in the treatment of renal fibrosis.
基金Supported by A grant from Innovative Research Institute for Cell Therapy Project,South Korea,No.A062260
文摘AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter(rAd-SP-rINSfur) into diabetic Lepr db/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control(rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve(AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk(AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice(AUC:9150.17 ± 1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.
基金Supported by the National Key Research and Development Program of China(No.2018AAA0103300,2017YFA0700900,2017YFA0700902,2017YFA0700901,2019AAA0103802,2020AAA0103802)。
文摘With the increasing of data size and model size,deep neural networks(DNNs)show outstanding performance in many artificial intelligence(AI)applications.But the big model size makes it a challenge for high-performance and low-power running DNN on processors,such as central processing unit(CPU),graphics processing unit(GPU),and tensor processing unit(TPU).This paper proposes a LOGNN data representation of 8 bits and a hardware and software co-design deep neural network accelerator LACC to meet the challenge.LOGNN data representation replaces multiply operations to add and shift operations in running DNN.LACC accelerator achieves higher efficiency than the state-of-the-art DNN accelerators by domain specific arithmetic computing units.Finally,LACC speeds up the performance per watt by 1.5 times,compared to the state-of-the-art DNN accelerators on average.
