Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil econom...Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil economy.The construction of non-natural and efficient biosynthesis routes of chemicals is an important goal of green biomanufacturing.Traditional methods that rely on experience are difficult to support the realization of this goal.However,with the rapid development of information technology,the intelligence of biomanufacturing has brought hope to achieve this goal.Retrobiosynthesis and computational enzyme design,as two of the main technologies in intelligent biomanufacturing,have developed rapidly in recent years and have made great achievements and some representative works have demonstrated the great value that the integration of the two fields may bring.To achieve the final integration of the two fields,it is necessary to examine the information,methods and tools from a bird’s-eye view,and to find a feasible idea and solution for establishing a connection point.For this purpose,this article briefly reviewed the main ideas,methods and tools of the two fields,and put forward views on how to achieve the integration of the two fields.展开更多
Formaldehyde(HCHO)is a common indoor gaseous pollutant,and long-term exposure to it may cause serious damage to the human immune system.Photocatalytic degradation of HCHO is a promising technique.However,most photocat...Formaldehyde(HCHO)is a common indoor gaseous pollutant,and long-term exposure to it may cause serious damage to the human immune system.Photocatalytic degradation of HCHO is a promising technique.However,most photocatalysts have the disadvantage of rapid recombination of photo-generated electron-hole pairs.In this work,the recombination of photogenerated electron holes was proposed to inhibit through the piezoelectric effect.A two-dimensional(2D)piezoelectric material,2H-MoS_(2),was selected to investigate the catalytic performance for HCHO degradation by the synergy of the piezoelectric and photocatalysis properties.The results show that the piezoelectric effect can induce the polarization in 2H-MoS_(2) and inhibit the recombination of photogenerated electron-hole pairs,thus improving the photogeneration of hydroxyl radicals for HCHO degradation.Therefore,the piezoelectric-photo-catalysis synergistic effect based on density functional theory(DFT)calculation was proposed to elucidate the HCHO degradation performance.This work could provide important guidance for the development of effective catalysts for HCHO degradation and the application of 2D piezoelectric materials.展开更多
Autophagy and apoptosis are both highly regulated biological processes that play essential roles in tissue homeostasis,development and diseases.Autophagy is also described as a mechanism of death pathways,however,the ...Autophagy and apoptosis are both highly regulated biological processes that play essential roles in tissue homeostasis,development and diseases.Autophagy is also described as a mechanism of death pathways,however,the precise mechanism of how autophagy links to cell death remains to be fully understood.Beclin 1 is a dual regulator for both autophagy and apoptosis.In this study we found that Beclin 1 was a substrate of caspase-3 with two cleavage sites at positions 124 and 149,respectively.Furthermore,the autophagosome formation occurred,followed by the appearance of morphological hallmarks of apoptosis after staurosporine treatment.The cleavage products of Beclin 1 reduced autophagy and promoted apoptosis in HeLa cells and the cells in which Beclin 1 was stably knocked down by specific shRNA.In addition,the cleavage of Beclin 1 resulted in abrogating the interaction between Bcl-2 with Beclin 1,which could be blocked by z-VAD-fmk.Thus,our results suggest that the cleavage of Beclin 1 by caspase-3 may contribute to inactivate autophagy leading towards augmented apoptosis.展开更多
Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal ceils...Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal ceils in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.展开更多
基金support from the National Nat-ural Science Foundation of China(U1663227,21861132017,21811530003,21878170).
文摘Biomanufacturing,which uses renewable resources as raw materials and uses biological processes to produce energy and chemicals,has long been regarded as a production model that replaces the unsustainable fossil economy.The construction of non-natural and efficient biosynthesis routes of chemicals is an important goal of green biomanufacturing.Traditional methods that rely on experience are difficult to support the realization of this goal.However,with the rapid development of information technology,the intelligence of biomanufacturing has brought hope to achieve this goal.Retrobiosynthesis and computational enzyme design,as two of the main technologies in intelligent biomanufacturing,have developed rapidly in recent years and have made great achievements and some representative works have demonstrated the great value that the integration of the two fields may bring.To achieve the final integration of the two fields,it is necessary to examine the information,methods and tools from a bird’s-eye view,and to find a feasible idea and solution for establishing a connection point.For this purpose,this article briefly reviewed the main ideas,methods and tools of the two fields,and put forward views on how to achieve the integration of the two fields.
基金financially supported by the National Natural Science Foundation of China(Nos.22176041 and 41807191)the Science and Technology Planning Project of Guangdong Province(No.2017B020216003)。
文摘Formaldehyde(HCHO)is a common indoor gaseous pollutant,and long-term exposure to it may cause serious damage to the human immune system.Photocatalytic degradation of HCHO is a promising technique.However,most photocatalysts have the disadvantage of rapid recombination of photo-generated electron-hole pairs.In this work,the recombination of photogenerated electron holes was proposed to inhibit through the piezoelectric effect.A two-dimensional(2D)piezoelectric material,2H-MoS_(2),was selected to investigate the catalytic performance for HCHO degradation by the synergy of the piezoelectric and photocatalysis properties.The results show that the piezoelectric effect can induce the polarization in 2H-MoS_(2) and inhibit the recombination of photogenerated electron-hole pairs,thus improving the photogeneration of hydroxyl radicals for HCHO degradation.Therefore,the piezoelectric-photo-catalysis synergistic effect based on density functional theory(DFT)calculation was proposed to elucidate the HCHO degradation performance.This work could provide important guidance for the development of effective catalysts for HCHO degradation and the application of 2D piezoelectric materials.
基金This work was supported by the National Basic Research Program(973 program project)(grants Nos.2007CB914800,2006CB910102)grants from National Natural Science Foundation of China(grant Nos.30630038 and 30400098)+1 种基金grants from Tianjin Natural Science foundation(09JCZDJC21200)to Y.Zhua project grant from Chinese Academy of Sciences KSCX2-YW-R-02 to Q.Chen.
文摘Autophagy and apoptosis are both highly regulated biological processes that play essential roles in tissue homeostasis,development and diseases.Autophagy is also described as a mechanism of death pathways,however,the precise mechanism of how autophagy links to cell death remains to be fully understood.Beclin 1 is a dual regulator for both autophagy and apoptosis.In this study we found that Beclin 1 was a substrate of caspase-3 with two cleavage sites at positions 124 and 149,respectively.Furthermore,the autophagosome formation occurred,followed by the appearance of morphological hallmarks of apoptosis after staurosporine treatment.The cleavage products of Beclin 1 reduced autophagy and promoted apoptosis in HeLa cells and the cells in which Beclin 1 was stably knocked down by specific shRNA.In addition,the cleavage of Beclin 1 resulted in abrogating the interaction between Bcl-2 with Beclin 1,which could be blocked by z-VAD-fmk.Thus,our results suggest that the cleavage of Beclin 1 by caspase-3 may contribute to inactivate autophagy leading towards augmented apoptosis.
基金We are grateful to Drs. Ted Dawson and Jian Feng for generously providing the plasmids. We are also grateful to Professor Mark Bartlam from Nankai University, Tianjin, China for a critical reading of the manuscript. The research was supported by the National Basic Research Program (973 Program) (No. 2011 CB910903) from MOST and project (Grant Nos. 81130045, 31471300, 31271529, 301520103904) from the National Natural Science Foundation of China.
文摘Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal ceils in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.