Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that gene...Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.展开更多
The sedimentary environment is inextricably linked to the macroscopic and microscopic characteristics of shale reservoirs,which influences shale gas accumulation significantly.This study discusses how the sedimentary ...The sedimentary environment is inextricably linked to the macroscopic and microscopic characteristics of shale reservoirs,which influences shale gas accumulation significantly.This study discusses how the sedimentary environment affects the organic-matter-rich shale reservoirs that have been deposited in typical marine,marine-continental transitional,and continental basins in China.The following four aspects were analyzed including shale rock type and thickness distribution,organic matter abundance and distribution,mineral composition and pore structure,and kerogen type and hydrocarbon generation potential.From continental to marine facies,the sedimentary setting of shales with high organic content generally ranges from shore-shallow lakes to deep lakes,deltas,tidal flat lagoons,shallow sea shelves,and deep or semi-deep seas.In deeper water,the clay mineral content decreases,but the brittleness index and siliceous content increase with darker shale color.Thick shales mostly were deposited in deep or semi-deep lakes,delta fronts,prodeltas,tidal flat lagoons,and deep or semi-deep seas from continental to marine basins.The primary factors influencing organic matter enrichment in deep-sea and deep-lake shales are redox conditions and high biological productivity under favorable sedimentary environments,whereas favorable factors for organic matter enrichment in transitional facies include warm-humid palaeoclimates and abundant debris inputs.Continental shale is characterized by the presence of intergranular and intragranular pores,a low pore volume and specific surface area,and a high average pore size and hydrocarbon potential.The kerogen types are complex in continental shales,with type I in deep lake shales and type III in lakeshore shales.Transitional shales occur mostly in coal-bearing strata with type III organic content,medium pore sizes,and hydrocarbon generation potential.The high specific surface area and pore volume,small pore size,and high brittle mineral content of marine shale facilitate the production of dissolution pores.Marine shales are mainly kerogen type I–II1 with relatively high maturity and low hydrocarbon production potential.By constructing an intrinsic link between the sedimentary environment and reservoir parameters,a sedimentary model of organic-rich shale under different depositional context should be summarized in the future,which can provide a foundation to analyze the geological circumstances of shale gas accumulation.展开更多
基金supported by the National Natural Science Foundation Council of China(82172386 and 81922081 to C.L.,82100943 to X.F.,82104216 to J.L.,and 82230081,82250710175 and 8226116039 to G.X.)the Department of Education of Guangdong Province(2021KTSCX104 to C.L.)+5 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab)(2020B1212030006 to A.L.)the Guangdong Provincial Science and Technology Innovation Council Grant(2017B030301018 to G.X.)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012164 to C.L.,and 2023A1515012000 to X.F.)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20210324104201005 to C.L.,JCYJ20220530115006014 to X.F.,JCYJ20230807095118035 to J.L.,and JCYJ20220818100617036 to G.X.)the Hong Kong General Research Fund(12102722 to A.L.)the Hong Kong RGC Themebased Research Scheme(T12-201/20-R to A.L.).
文摘Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.
基金supported by the National Natural Science Foundation of China(Grant No.42102223)the China Postdoctoral Science Foundation(Nos.2021M693844,2022T150284).
文摘The sedimentary environment is inextricably linked to the macroscopic and microscopic characteristics of shale reservoirs,which influences shale gas accumulation significantly.This study discusses how the sedimentary environment affects the organic-matter-rich shale reservoirs that have been deposited in typical marine,marine-continental transitional,and continental basins in China.The following four aspects were analyzed including shale rock type and thickness distribution,organic matter abundance and distribution,mineral composition and pore structure,and kerogen type and hydrocarbon generation potential.From continental to marine facies,the sedimentary setting of shales with high organic content generally ranges from shore-shallow lakes to deep lakes,deltas,tidal flat lagoons,shallow sea shelves,and deep or semi-deep seas.In deeper water,the clay mineral content decreases,but the brittleness index and siliceous content increase with darker shale color.Thick shales mostly were deposited in deep or semi-deep lakes,delta fronts,prodeltas,tidal flat lagoons,and deep or semi-deep seas from continental to marine basins.The primary factors influencing organic matter enrichment in deep-sea and deep-lake shales are redox conditions and high biological productivity under favorable sedimentary environments,whereas favorable factors for organic matter enrichment in transitional facies include warm-humid palaeoclimates and abundant debris inputs.Continental shale is characterized by the presence of intergranular and intragranular pores,a low pore volume and specific surface area,and a high average pore size and hydrocarbon potential.The kerogen types are complex in continental shales,with type I in deep lake shales and type III in lakeshore shales.Transitional shales occur mostly in coal-bearing strata with type III organic content,medium pore sizes,and hydrocarbon generation potential.The high specific surface area and pore volume,small pore size,and high brittle mineral content of marine shale facilitate the production of dissolution pores.Marine shales are mainly kerogen type I–II1 with relatively high maturity and low hydrocarbon production potential.By constructing an intrinsic link between the sedimentary environment and reservoir parameters,a sedimentary model of organic-rich shale under different depositional context should be summarized in the future,which can provide a foundation to analyze the geological circumstances of shale gas accumulation.
