With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as ...With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries.Previously,we developed a coronavirus disease 2019(COVID-19)protein subunit vaccine ZF2001?based on the tandem homo-prototype receptor-binding domain(RBD)-dimer of the SARS-CoV-2 spike protein.We upgraded the antigen into a hetero-chimeric prototype(PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms.Herein,we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine(Ⅳ)in mice.Our data demonstrated that the chi-meric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the vari-ants,and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice,shedding light on the antigen design for the next-generation COVID-19 vaccines.展开更多
Synthetic molecules that can mediate the coupled transport of Cl^(-) with K^(+) and/or Na+across the lipid bilayers have aroused great interest due to their potential as a novel therapeutic strategy by disrupting cell...Synthetic molecules that can mediate the coupled transport of Cl^(-) with K^(+) and/or Na+across the lipid bilayers have aroused great interest due to their potential as a novel therapeutic strategy by disrupting cellular ion homeostasis.Based on the structural advantages of molecular rotaxanes,we herein show that two rotaxane-based transporters[2]R and[3]R induce coupled K^(+)/Cl^(-) channel transport by introducing Cl^(-) recognition sites in the thread and K^(+) binding group in the wheel,respectively.The welldesigned molecular structures allow the insertion of unimolecular rotaxanes into the lipid bilayer,thus achieving effective ion transport by means of thermodynamically controlled movement and driven by the difference in ion concentration inside and outside the vesicles.In addition,the use of a three-component rotaxane can accelerate ion transport through a cooperative shuttlerelay mechanism in which two wheels move along the thread in the lipid membrane,thereby enabling[3]R to have higher ion transport capacity.This work represents a major advance in the use of rotaxane molecules to accomplish more complex and effective tasks.展开更多
The Lower Triassic Feixianguan Formation at the well-known Puguang gasfield in the northeastern Sichuan Basin of southwest China produces a representa- tive oolitic reservoir, which has been the biggest marinesourced ...The Lower Triassic Feixianguan Formation at the well-known Puguang gasfield in the northeastern Sichuan Basin of southwest China produces a representa- tive oolitic reservoir, which has been the biggest marinesourced gasfield so far in China （discovered in 2003 with proven gas reserves greater than 350× 10^8 m3）. This study combines core, thin section, and scanning electron microscopy observations, and geochemical analysis （C, O, and Sr isotopes） in order to investigate the basic characteristics and formation mechanisms of the reservoir. Observations indicate that platform margin oolitic dolomites are the most important reservoir rocks. Porosity is dominated by intergranular and intragranular solution, and moldic pore. The dolomites are characterized by medium porosity and permeability, averaging at approximately 9% and 29.7 mD, respectively. ^87Sr/^86Sr （0.707536-0.707934） and δ^13CpDB （1.8 ‰--3.5 ‰） isotopic values indicate that the dolomitization fluid is predominantly concentrated seawater by evaporation, and the main mechanism for the oolitic dolomite formation is seepage reflux at an early stage of eodiagenesis. Both sedimentation and diagenesis （e.g., dolomitization and dissolution） have led to the formation of high-quality rocks to different degrees. Dolomite formation may have little contribution, karst may have had both positive and negative influences, and burial dissolution-TSR （thermochemical sulfate reduction） may not impact widely. The preservation of primary intergranular pores and dissolution by meteoric or mixed waters at the early stage of eogenesis are the main influences. This study may assist oil and gas explorationactivities in the Puguang area and in other areas withdolomitic reservoirs.展开更多
With increasing industrial activities,mercury has been largely discharged into environment and caused serious environmental problems.The growing level of mercury pollution has become a huge threat to human health due ...With increasing industrial activities,mercury has been largely discharged into environment and caused serious environmental problems.The growing level of mercury pollution has become a huge threat to human health due to its significant biotoxicity.Therefore,the simple and fast means for on-site monitoring discharged mercury pollution are highly necessary to protect human beings from its pernicious effects in time.Herein,a"turn off"fluorescent biosensor(mCherry L199 C)for sensing Hg2+was successfully designed based on direct modification of the chromophore environment of fluorescent protein mCherry.For rapid screening and characterization,the designed variant of mCherry(mCherry L199 C)was directly expressed on outer-membrane of Escherichia coli cells by cell surface display technique.The fluorescent biosensor was characterized to have favorable response to Hg2+at micromole level among other metal ions and over a broad pH range.Further,the cells of the fluorescent biosensor were encapsulated in alginate hydrogel to develop the cells-alginate hydrogel-based paper.The cells-alginate hydrogel-based paper could detect mercury pollution in 5 min with simple operation process and inexpensive equipment,and it could keep fluorescence and activity stable at 4℃ for 24 hr,which would be a high-throughput screening tool in preliminarily reporting the presence of mercury pollution in natural setting.展开更多
基金supported by the National Key R&D Program of China(2022YFC2303403)the National Natural Science Foundation of China(82225021 and 32171428)the CAS Young Scientists in Basic Research(YSBR-010)。
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(grant number XDB29040203)the National Key Research and Development Program of China(grant number 2021YFA1301404 and 2020YFA0907102)+2 种基金the National Natural Science Foundation of China(grant numbers 82225021 and 32171428)In addition,Qihui Wang was supported by the CAS Project for Young Scientists in Basic Research(grant number YSBR-010)the Youth Innovation Promotion Association of the CAS(grant number Y2022037).We thank Professor Xiao Zhao from the National Center for Nanoscience and Technology for sharing the LNP encapsulation and DLS platforms.We thank Dr.Kun Xu for his help during the revision of this manuscript.We thank Linjie Li for sharing recombinant RBD proteins.We thank the Institutional Center for Shared Technology and Facilitates in the Institute of Microbiology,CAS,and the Institute of Zoology,CAS.
文摘With continuous mutations of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the severe immune escape of Omicron sub-variants urges the development of next-generation broad-spectrum vaccines,especially as booster jabs after high-level vaccination coverage of inactivated vaccines in China and many other countries.Previously,we developed a coronavirus disease 2019(COVID-19)protein subunit vaccine ZF2001?based on the tandem homo-prototype receptor-binding domain(RBD)-dimer of the SARS-CoV-2 spike protein.We upgraded the antigen into a hetero-chimeric prototype(PT)-Beta or Delta-BA.1 RBD-dimer to broaden the cross-protection efficacy and prove its efficiency with protein subunit and mRNA vaccine platforms.Herein,we further explored the hetero-chimeric RBD-dimer mRNA vaccines and evaluated their broad-spectrum activities as booster jabs following two doses of inactivated vaccine(Ⅳ)in mice.Our data demonstrated that the chi-meric vaccines significantly boosted neutralizing antibody levels and specific T-cell responses against the vari-ants,and PT-Beta was superior to Delta-BA.1 RBD as a booster in mice,shedding light on the antigen design for the next-generation COVID-19 vaccines.
基金supported by the National Natural Science Foundation of China(22171085)the Shanghai Science Technology Communication(21ZR1415500)Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission,Grant 2021 Sci&Tech 03-28)。
文摘Synthetic molecules that can mediate the coupled transport of Cl^(-) with K^(+) and/or Na+across the lipid bilayers have aroused great interest due to their potential as a novel therapeutic strategy by disrupting cellular ion homeostasis.Based on the structural advantages of molecular rotaxanes,we herein show that two rotaxane-based transporters[2]R and[3]R induce coupled K^(+)/Cl^(-) channel transport by introducing Cl^(-) recognition sites in the thread and K^(+) binding group in the wheel,respectively.The welldesigned molecular structures allow the insertion of unimolecular rotaxanes into the lipid bilayer,thus achieving effective ion transport by means of thermodynamically controlled movement and driven by the difference in ion concentration inside and outside the vesicles.In addition,the use of a three-component rotaxane can accelerate ion transport through a cooperative shuttlerelay mechanism in which two wheels move along the thread in the lipid membrane,thereby enabling[3]R to have higher ion transport capacity.This work represents a major advance in the use of rotaxane molecules to accomplish more complex and effective tasks.
文摘The Lower Triassic Feixianguan Formation at the well-known Puguang gasfield in the northeastern Sichuan Basin of southwest China produces a representa- tive oolitic reservoir, which has been the biggest marinesourced gasfield so far in China （discovered in 2003 with proven gas reserves greater than 350× 10^8 m3）. This study combines core, thin section, and scanning electron microscopy observations, and geochemical analysis （C, O, and Sr isotopes） in order to investigate the basic characteristics and formation mechanisms of the reservoir. Observations indicate that platform margin oolitic dolomites are the most important reservoir rocks. Porosity is dominated by intergranular and intragranular solution, and moldic pore. The dolomites are characterized by medium porosity and permeability, averaging at approximately 9% and 29.7 mD, respectively. ^87Sr/^86Sr （0.707536-0.707934） and δ^13CpDB （1.8 ‰--3.5 ‰） isotopic values indicate that the dolomitization fluid is predominantly concentrated seawater by evaporation, and the main mechanism for the oolitic dolomite formation is seepage reflux at an early stage of eodiagenesis. Both sedimentation and diagenesis （e.g., dolomitization and dissolution） have led to the formation of high-quality rocks to different degrees. Dolomite formation may have little contribution, karst may have had both positive and negative influences, and burial dissolution-TSR （thermochemical sulfate reduction） may not impact widely. The preservation of primary intergranular pores and dissolution by meteoric or mixed waters at the early stage of eogenesis are the main influences. This study may assist oil and gas explorationactivities in the Puguang area and in other areas withdolomitic reservoirs.
基金supported by the Natural Science Foundation of Guangxi Province(No.2018JJB120049)National Natural Science Foundation of China(No.31800631)+1 种基金the BAGUI Scholar Program of Guangxi Province of China。
文摘With increasing industrial activities,mercury has been largely discharged into environment and caused serious environmental problems.The growing level of mercury pollution has become a huge threat to human health due to its significant biotoxicity.Therefore,the simple and fast means for on-site monitoring discharged mercury pollution are highly necessary to protect human beings from its pernicious effects in time.Herein,a"turn off"fluorescent biosensor(mCherry L199 C)for sensing Hg2+was successfully designed based on direct modification of the chromophore environment of fluorescent protein mCherry.For rapid screening and characterization,the designed variant of mCherry(mCherry L199 C)was directly expressed on outer-membrane of Escherichia coli cells by cell surface display technique.The fluorescent biosensor was characterized to have favorable response to Hg2+at micromole level among other metal ions and over a broad pH range.Further,the cells of the fluorescent biosensor were encapsulated in alginate hydrogel to develop the cells-alginate hydrogel-based paper.The cells-alginate hydrogel-based paper could detect mercury pollution in 5 min with simple operation process and inexpensive equipment,and it could keep fluorescence and activity stable at 4℃ for 24 hr,which would be a high-throughput screening tool in preliminarily reporting the presence of mercury pollution in natural setting.
