The methanol-to-olefins(MTO)process has the potential to bridge future gaps in the supply of sustainable lower olefins.Promoting the selectivity of propylene and ethylene and revealing the catalytic role of active sit...The methanol-to-olefins(MTO)process has the potential to bridge future gaps in the supply of sustainable lower olefins.Promoting the selectivity of propylene and ethylene and revealing the catalytic role of active sites are challenging goals in MTO reactions.Here,we report a novel heteroatomic silicoaluminophosphate(SAPO)zeolite,SAPO-34-Ta,which incorporates active tantalum(V)sites within the framework to afford an optimal distribution of acidity.SAPO-34-Ta exhibits a remarkable total selectivity of 85.8%for propylene and ethylene with a high selectivity of 54.9%for propylene on full conversion of methanol at 400°C.In situ and operando synchrotron powder X-ray diffraction,diffuse reflectance infrared Fourier transform spectroscopy and inelastic neutron scattering,coupled with theoretical calculations,reveal trimethyloxonium as the key reaction intermediate,promoting the formation of first carbon-carbon bonds in olefins.The tacit cooperation between tantalum(V)and Brønsted acid sites within SAPO-34 provides an efficient platform for selective production of lower olefins from methanol.展开更多
Progranulin(PGRN)is a growth factor that is involved in the progression of multiple tumors.However,the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear.The expression level of PGRN was...Progranulin(PGRN)is a growth factor that is involved in the progression of multiple tumors.However,the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear.The expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma(NSCLC)patients.The proliferation,apoptosis,migration,and invasion of NSCLC cells were assessed by the MTT assay,Western blot,degree of wound healing,and Transwell assays.A nude mouse xenograft model was used to validate the role of PGRN in vivo.The expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma;by contrast,no difference was observed in female patients.The overexpression of PGRN promoted the proliferation and anti-apoptosis of H520(derived from lung squamous cell carcinoma)cells,whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549(derived from lung adenocarcinoma)cells.Copanlisib(targeting PI3K)inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein;the PI3K agonist 740 YeP partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 cells.PGRN increased the expression of Ki-67,PCNA,and Bcl-2 in vivo.PGRN inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis;PGRN positivity correlated with lung adenocarcinoma.PGRN is a potential biomarker for the treatment and diagnosis of NSCLC,especially in lung adenocarcinoma.展开更多
Progranulin(PGRN)is a multifunctional growth factor involved in many physiolog-ical processes and disease states.The apparent protective role of PGRN and the importance of chondrocyte autophagic function in the progre...Progranulin(PGRN)is a multifunctional growth factor involved in many physiolog-ical processes and disease states.The apparent protective role of PGRN and the importance of chondrocyte autophagic function in the progression of osteoarthritis(OA)led us to investi-gate the role of PGRN in the regulation of chondrocyte autophagy.PGRN knockout chondro-cytes exhibited a deficient autophagic response with limited induction following rapamycin,serum starvation,and IL-1b-induced autophagy.PGRN-mediated anabolism and suppression of IL-1b-induced catabolism were largely abrogated in the presence of the BafA1 autophagy inhibitor.Mechanistically,during the process of OA,PGRN and the ATG5eATG12 conjugate form a protein complex;PGRN regulates autophagy in chondrocytes and OA through,at least partially,the interactions between PGRN and the ATG5eATG12 conjugate.Furthermore,the ATG5eATG12 conjugate is critical for cell proliferation and apoptosis.Knockdown or knockout of ATG5 reduces the expression of ATG5eATG12 conjugate and inhibits the chondroprotective effect of PGRN on anabolism and catabolism.Overexpression of PGRN partially reversed this effect.In brief,the PGRN-mediated regulation of chondrocyte autophagy plays a key role in the chondroprotective role of PGRN in OA.Such studies provide new insights into the pathogen-esis of OA and PGRN-associated autophagy in chondrocyte homeostasis.展开更多
Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes,in which the Indian hedgehog(IHH)and parathyroid hormone-related protein-parathyroid hormone...Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes,in which the Indian hedgehog(IHH)and parathyroid hormone-related protein-parathyroid hormone-1 receptor(PTHrP-PTH1R)feedback loop is crucial.The inositol-requiring enzyme 1a/X-box-binding protein-1 spliced(IRE1α/XBP1s)branch of the unfolded protein response(UPR)is essential for normal cartilage development.However,the precise role of ER stress effector IRE1α,encoded by endoplasmic reticulum to nucleus signaling 1(ERN1),in skeletal development remains unknown.Herein,we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone growth.ERN1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth plates.Its deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and differentiation.XBP1s,produced by p-IRE1α-mediated splicing,binds and up-regulates PTH1R and IHH,which coordinate cartilage development.Meanwhile,ER stress cannot be activated normally in ERN1-deficient chondrocytes.In conclusion,ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER stress.ERN1 may have a potential role as a new target for cartilage growth and maturation.展开更多
基金University of Manchester,the National Natural Science Foundation of China and BNLMS for funding,and the EPSRC for funding of the EPSRC National EPR Facility at Manchester(EP/W014532/1 and EP/X034623/1)We are grateful to the STFC/ISIS Facility and Diamond Light Source for access to the beamlines TOSCA/MAPS,and I11/B18/B22,respectively+8 种基金We are grateful to the STFC/ISIS Facility and Diamond Light Source for access to the beamlines TOSCA/MAPS,and I11/B18/B22,respectivelyWe acknowledge the UK catalysis Hub Block Allocation Group(BAG)Programme Mode Application for provision of beamtime at B18 for collection of the data presented in this work and the initial discussion of the dataThe UK Catalysis Hub is kindly thanked for resources and support provided via our membership of the UK Catalysis Hub Consortium and funded by EPSRC grant:EP/R026939,EP/R026815,EP/R026645,EP/R027129 and EP/M013219(biocatalysis)We acknowledge the support of The University of Manchester's Dalton Cumbrian Facility(DCF),a partner in the National Nuclear User FacilityWe recognise Dr.R.Edge for the assistance during the 60Co-irradiation processesWe thank M.Kibble for help at ISIS beamlinesTEM access was supported by the Henry Royce Institute for Advanced Materials,funded through EPSRC grants EP/R00661X,EP/S019367,EP/P025021 and EP/P025498Zhaodong Zhu thanks the President's Doctoral Scholar award of University of Manchester for fundingMeng He and Lutong Shan thank the China Scholarship Council(CSC)for funding.
文摘The methanol-to-olefins(MTO)process has the potential to bridge future gaps in the supply of sustainable lower olefins.Promoting the selectivity of propylene and ethylene and revealing the catalytic role of active sites are challenging goals in MTO reactions.Here,we report a novel heteroatomic silicoaluminophosphate(SAPO)zeolite,SAPO-34-Ta,which incorporates active tantalum(V)sites within the framework to afford an optimal distribution of acidity.SAPO-34-Ta exhibits a remarkable total selectivity of 85.8%for propylene and ethylene with a high selectivity of 54.9%for propylene on full conversion of methanol at 400°C.In situ and operando synchrotron powder X-ray diffraction,diffuse reflectance infrared Fourier transform spectroscopy and inelastic neutron scattering,coupled with theoretical calculations,reveal trimethyloxonium as the key reaction intermediate,promoting the formation of first carbon-carbon bonds in olefins.The tacit cooperation between tantalum(V)and Brønsted acid sites within SAPO-34 provides an efficient platform for selective production of lower olefins from methanol.
基金This research was supported by Chongqing Technology Innovation and application development special fund(No.cstc2019jscx-msxmX0095)National Natural Science Foundation of China(No.NSFC 81672103)The authors are responsible for the results and opinions provided by this research,and the sponsor is not responsible for the content published.
文摘Progranulin(PGRN)is a growth factor that is involved in the progression of multiple tumors.However,the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear.The expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma(NSCLC)patients.The proliferation,apoptosis,migration,and invasion of NSCLC cells were assessed by the MTT assay,Western blot,degree of wound healing,and Transwell assays.A nude mouse xenograft model was used to validate the role of PGRN in vivo.The expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma;by contrast,no difference was observed in female patients.The overexpression of PGRN promoted the proliferation and anti-apoptosis of H520(derived from lung squamous cell carcinoma)cells,whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549(derived from lung adenocarcinoma)cells.Copanlisib(targeting PI3K)inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein;the PI3K agonist 740 YeP partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 cells.PGRN increased the expression of Ki-67,PCNA,and Bcl-2 in vivo.PGRN inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis;PGRN positivity correlated with lung adenocarcinoma.PGRN is a potential biomarker for the treatment and diagnosis of NSCLC,especially in lung adenocarcinoma.
基金supported by the National Natural Science Foundation of China(No.81672209)Chongqing Science and Technology Bureau(No.cstc2020jcyj-msxmX0175),ChinaChongqing Human Resources and Social Security Bureau(No.2018-389),China.
文摘Progranulin(PGRN)is a multifunctional growth factor involved in many physiolog-ical processes and disease states.The apparent protective role of PGRN and the importance of chondrocyte autophagic function in the progression of osteoarthritis(OA)led us to investi-gate the role of PGRN in the regulation of chondrocyte autophagy.PGRN knockout chondro-cytes exhibited a deficient autophagic response with limited induction following rapamycin,serum starvation,and IL-1b-induced autophagy.PGRN-mediated anabolism and suppression of IL-1b-induced catabolism were largely abrogated in the presence of the BafA1 autophagy inhibitor.Mechanistically,during the process of OA,PGRN and the ATG5eATG12 conjugate form a protein complex;PGRN regulates autophagy in chondrocytes and OA through,at least partially,the interactions between PGRN and the ATG5eATG12 conjugate.Furthermore,the ATG5eATG12 conjugate is critical for cell proliferation and apoptosis.Knockdown or knockout of ATG5 reduces the expression of ATG5eATG12 conjugate and inhibits the chondroprotective effect of PGRN on anabolism and catabolism.Overexpression of PGRN partially reversed this effect.In brief,the PGRN-mediated regulation of chondrocyte autophagy plays a key role in the chondroprotective role of PGRN in OA.Such studies provide new insights into the pathogen-esis of OA and PGRN-associated autophagy in chondrocyte homeostasis.
基金supported by the National Natural Science Foundation of China(No.81672209,81871769,82272550)the Chongqing Science and Technology Bureau(China)(No.cstc2021jcyj-bshX0214).
文摘Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes,in which the Indian hedgehog(IHH)and parathyroid hormone-related protein-parathyroid hormone-1 receptor(PTHrP-PTH1R)feedback loop is crucial.The inositol-requiring enzyme 1a/X-box-binding protein-1 spliced(IRE1α/XBP1s)branch of the unfolded protein response(UPR)is essential for normal cartilage development.However,the precise role of ER stress effector IRE1α,encoded by endoplasmic reticulum to nucleus signaling 1(ERN1),in skeletal development remains unknown.Herein,we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone growth.ERN1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth plates.Its deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and differentiation.XBP1s,produced by p-IRE1α-mediated splicing,binds and up-regulates PTH1R and IHH,which coordinate cartilage development.Meanwhile,ER stress cannot be activated normally in ERN1-deficient chondrocytes.In conclusion,ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER stress.ERN1 may have a potential role as a new target for cartilage growth and maturation.
