ChatG PT,an artificial intelligence generated content (AIGC) model developed by OpenAI,has attracted worldwide attention for its capability of dealing with challenging language understanding and generation tasks in th...ChatG PT,an artificial intelligence generated content (AIGC) model developed by OpenAI,has attracted worldwide attention for its capability of dealing with challenging language understanding and generation tasks in the form of conversations.This paper briefly provides an overview on the history,status quo and potential future development of ChatGPT,helping to provide an entry point to think about ChatGPT.Specifically,from the limited open-accessed resources,we conclude the core techniques of ChatGPT,mainly including large-scale language models,in-context learning,reinforcement learning from human feedback and the key technical steps for developing ChatGPT.We further analyze the pros and cons of ChatGPT and we rethink the duality of ChatGPT in various fields.Although it has been widely acknowledged that ChatGPT brings plenty of opportunities for various fields,mankind should still treat and use ChatG PT properly to avoid the potential threat,e.g.,academic integrity and safety challenge.Finally,we discuss several open problems as the potential development of ChatGPT.展开更多
Physalis. alkekengi fruit has long been used in traditional Chinese medicine for tumor therapy. In the present study, using plasmids that encode ovalbumin (OVA) gene, we investigate the adjuvant activity of a polysacc...Physalis. alkekengi fruit has long been used in traditional Chinese medicine for tumor therapy. In the present study, using plasmids that encode ovalbumin (OVA) gene, we investigate the adjuvant activity of a polysaccharide fraction (PPSB) isolated from P.alkekengi fruit. Formulation by simple procedures of mixing of the OVA-encoding pCI-neo-sOVA plasmid with PPSB not only induced specific antibody responses, but also induced antigen-specific cytotoxic T lymphocyte (CTL) responses (Graph abstract). Furthermore, immunization using this vaccine prevented the growth of OVA-expressing B16-OVA tumor cell growth in the immunized mice. Thus, we provide evidence supporting the adjuvant activity of PPSB in DNA vaccine against tumor.展开更多
The ionic liquid,as a new treatment agent,has been increasingly applied in oil fields due to its strong temperature resistance,good solubility and high surface activity.In this paper,we systematically discuss the acti...The ionic liquid,as a new treatment agent,has been increasingly applied in oil fields due to its strong temperature resistance,good solubility and high surface activity.In this paper,we systematically discuss the action mechanism and application effect of ionic liquids in oilfield chemistry.Ionic liquids can inhibit shale hydration expansion and reduce fluid loss through adsorption and intercalation,inhibit the formation of natural gas hydrate through imidazole five-membered ring structure as a space barrier,reduce viscosity of heavy oil by breaking chemical bonds of heavy oil macromolecules and charge transfer,improve oil displacement efficiency by forming ions pairs with carboxyl groups in crude oil,demulsify by forming channels between dispersed water droplets,acidify the formation by reacting with water to produce acid,interacts with organic material through weak hydrogen bonds and extracts it from oilfield wastewater,desulphurize by inserting sulfide molecules into the“stack”structure and form liquid inclusion complex,inhibit corrosion by forming a protective film on the metal surface.Based on the above aspects,the development direction of ionic liquids is proposed.The application of ionic liquids in oilfield chemistry is still in its infancy.It is urgent to fully explore the application performance of ionic liquids in oilfield chemistry,which also provides theoretical and technical supports for efficient reservoir development.展开更多
Mesenchymal stem cell(MSC)-based therapies have emerged as promising methods for regenerative medicine;however,how to precisely enhance their tissue repair effects is still a major question in the field.Circulating ex...Mesenchymal stem cell(MSC)-based therapies have emerged as promising methods for regenerative medicine;however,how to precisely enhance their tissue repair effects is still a major question in the field.Circulating extracellular vesicles(EVs)from diseased states carry diverse pathological information and affect the functions of recipient cells.Based on this unique property,we report that disease-derived circulating EV(disease-EV)preconditioning is a potent strategy for precisely enhancing the tissue repair potency of MSCs in diverse disease models.Briefly,plasma EVs from lung or kidney tissue injuries were shown to contain distinctly enriched molecules and were shown to induce tissue injury-specific gene expression responses in cultured MSCs.Disease-EV preconditioning improved the performance(including proliferation,migration,and growth factor production)of MSCs through metabolic reprogramming(such as via enhanced oxidative phosphorylation and lipid metabolism)without inducing an adverse immune response.Consequently,compared with normal MSCs,disease-EV-preconditioned MSCs exhibited superior tissue repair effects(including anti-inflammatory and antiapoptotic effects)in diverse types of tissue injury(such as acute lung or kidney injury).Disease-derived EVs may serve as a type of“off-the-shelf”product due to multiple advantages,such as flexibility,stability,long-term storage,and ease of shipment and use.This study highlights the idea that disease-EV preconditioning is a robust strategy for precisely enhancing the regenerative capacity of MSC-based therapies.展开更多
Graphene is a single atom thick crystal composed of carbon atoms.It is the lightest,thinnest,strongest material that conducts heat and electricity well heretofore.In terms of application,by introducing oxygen-containi...Graphene is a single atom thick crystal composed of carbon atoms.It is the lightest,thinnest,strongest material that conducts heat and electricity well heretofore.In terms of application,by introducing oxygen-containing groups,graphene can be well dispersed in solvents,can be chemically modified and functionalized,or connected with other electroactive substances through covalent bond or non-covalent bond to form composite materials,which is conducive to further processing and promotion.The application of graphene in oilfield chemistry started late,but developed rapidly.Graphene has played an active role in drilling fluid,cementing fluid,fracturing fluid,displacement fluid and other oilfield working fluids.It can enhance the temperature and salt resistance of working fluid and improve the effect of working fluid.In this paper,several directions of graphene applications in oilfield chemistry,such as modified graphene,graphene copolymers and graphene nanoparticles,are reviewed in detail from the synthesis methods,action mechanisms and effects of graphene and its derivatives,and the frontier cases at this stage are given.On the basis of the existing research,suggestions for the development direction of graphene materials in oilfield chemistry are given for a variety of graphene materials,aiming to provide guidance for the application of graphene in oilfield chemistry.展开更多
Severe acute pancreatitis-associated acute lung injury(SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI;however, the mechanism remains unclear. We report that ...Severe acute pancreatitis-associated acute lung injury(SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI;however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely,emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury,and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.展开更多
To enhance the fuel economy of a vehicle powered by a gasoline engine under road conditions,an energy flow test of a vehicle was performed experimentally under the New European Driving Cycle of cold start.The energy d...To enhance the fuel economy of a vehicle powered by a gasoline engine under road conditions,an energy flow test of a vehicle was performed experimentally under the New European Driving Cycle of cold start.The energy distributions and related influencing factors were analyzed using the test data.Results show that the effective power and thermal efficiency are mainly affected by the engine load except in the early stage of the New European Driving Cycle.Because of the retarded CA50 and longer CA10-90,the effective thermal efficiency is lower in the early phase of driving conditions.Initially,the heat transfer loss mainly comprises the loss of the heating,ventilation,and air conditioning system.The radiator then plays the major role,with its percentage affected by the engine load and decreasing under the extra-urban driving cycle.The exhaust gas loss is decided by the temperature and flow rate of the exhaust gas,while its percentage is mainly affected by the temperature of the exhaust gas.In the early phase of driving conditions,the retarded spark advance angle leads to a higher temperature of the exhaust gas and a greater exhaust gas loss.The pumping loss and its percentage are mainly determined by the engine speed under the urban driving cycle,and both decrease under the extra-urban driving cycle except at maximum vehicle speed.展开更多
The maternal immune system is vital in maintaining immunotolerance to the semiallogeneic fetus for a successful pregnancy.Although studies have shown that myeloid-derived suppressor cells(MDSCs)play an important role ...The maternal immune system is vital in maintaining immunotolerance to the semiallogeneic fetus for a successful pregnancy.Although studies have shown that myeloid-derived suppressor cells(MDSCs)play an important role in maintaining feto-maternal tolerance,little is known about the role of MDSCs in pregnancies with intrauterine growth retardation(IUGR).Here,we reported that the activation of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)during pregnancy was closely associated with fetal growth.In humans,class E scavenger receptor 1(SR-E1),a distinct marker for human PMN-MDSCs,was used to investigate PMN-MDSC function during pregnancy.Continuous activation of SR-E1+PMN-MDSCs was observed in all stages of pregnancy,accompanied by high cellular levels of ROS and arginase-1 activity,mediated through STAT6 signaling.However,SR-E1+PMN-MDSCs in pregnancies with IUGR showed significantly lower suppressive activity,lower arginase-1 activity and ROS levels,and decreased STAT6 phosphorylation level,which were accompanied by an increase in inflammatory factors,compared with those in normal pregnancies.Moreover,the population of SR-E1+PMN-MDSCs was negatively correlated with the adverse outcomes of newborns from pregnancies with IUGR.In mice,decreases in cell population,suppressive activity,target expression levels,and STAT6 phosphorylation levels were also observed in the pregnancies with IUGR compared with the normal pregnancies,which were rescued by the adoptive transfer of PMN-MDSCs from pregnant mice.Interestingly,the growth-promoting factors(GPFs)secreted by placental PMN-MDSCs in both humans and mice play a vital role in fetal development.These findings collectively support that PMN-MDSCs have another new role in pregnancy,which can improve adverse neonatal outcomes.展开更多
During the drilling process for oil and gas production,a larger number of drilling fluids invade the formation,causing severe formation damage and wellbore collapsing,which seriously hinders the efficient production o...During the drilling process for oil and gas production,a larger number of drilling fluids invade the formation,causing severe formation damage and wellbore collapsing,which seriously hinders the efficient production of deep oil and gas.Although several plugging agents have been developed for efficient fracture sealing in recent years,the development of high-performance plugging agents with self-adaptive ability and high-temperature resistance remain a challenge.Herein,we report the synthesis of an internal rigid and external flexible plugging agent PANS by reversed-phase emulsion polymerization with nano-silica as the rigid core and poly(acrylamide-co-N-vinylpyrrolidone)as a flexible shell.The plugging agent has a median particle size of 10.5μm and can self-adapt to seal the microfractures and fractures in the formation,leading to an effective reduction in the filtration loss of bentonite water-based drilling fluid under both low temperature and low pressure(LTLP)and high temperature and high pressure(HTHP)conditions.In addition,compared with the neat nano-silica(500 nm),the sealing efficiency of PANS toward 100–120 mesh sand bed was increased by 71.4%after hot rolling at 180°C.展开更多
Osteoporosis(OP)is a systemic skeletal disease that primarily affects the elderly population,which greatly increases the risk of fractures.Here we report that Kindlin-2 expression in adipose tissue increases during ag...Osteoporosis(OP)is a systemic skeletal disease that primarily affects the elderly population,which greatly increases the risk of fractures.Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass.Kindlin-2 specific deletion(K2KO)controlled by Adipoq-Cre mice or adipose tissue-targeting AAV(AAV-Rec2-CasRx-sgK2)significantly increases bone mass.Mechanistically,Kindlin-2 promotes peroxisome proliferator-activated receptor gamma(PPARγ)activation and downstream fatty acid binding protein 4(FABP4)expression through stabilizing fatty acid synthase(FAS),and increased FABP4 inhibits insulin expression and decreases bone mass.Kindlin-2 inhibition results in accelerated FAS degradation,decreased PPARγactivation and FABP4 expression,and therefore increased insulin expression and bone mass.Interestingly,we find that FABP4 is increased while insulin is decreased in serum of OP patients.Increased FABP4 expression through PPARγactivation by rosiglitazone reverses the high bone mass phenotype of K2KO mice.Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice.Collectively,our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.展开更多
基金supported by National Key Research and Development Program of China (2021YFB1714300)National Natural Science Foundation of China (62293502, 61831022, 61976211)Youth Innovation Promotion Association CAS。
文摘ChatG PT,an artificial intelligence generated content (AIGC) model developed by OpenAI,has attracted worldwide attention for its capability of dealing with challenging language understanding and generation tasks in the form of conversations.This paper briefly provides an overview on the history,status quo and potential future development of ChatGPT,helping to provide an entry point to think about ChatGPT.Specifically,from the limited open-accessed resources,we conclude the core techniques of ChatGPT,mainly including large-scale language models,in-context learning,reinforcement learning from human feedback and the key technical steps for developing ChatGPT.We further analyze the pros and cons of ChatGPT and we rethink the duality of ChatGPT in various fields.Although it has been widely acknowledged that ChatGPT brings plenty of opportunities for various fields,mankind should still treat and use ChatG PT properly to avoid the potential threat,e.g.,academic integrity and safety challenge.Finally,we discuss several open problems as the potential development of ChatGPT.
文摘Physalis. alkekengi fruit has long been used in traditional Chinese medicine for tumor therapy. In the present study, using plasmids that encode ovalbumin (OVA) gene, we investigate the adjuvant activity of a polysaccharide fraction (PPSB) isolated from P.alkekengi fruit. Formulation by simple procedures of mixing of the OVA-encoding pCI-neo-sOVA plasmid with PPSB not only induced specific antibody responses, but also induced antigen-specific cytotoxic T lymphocyte (CTL) responses (Graph abstract). Furthermore, immunization using this vaccine prevented the growth of OVA-expressing B16-OVA tumor cell growth in the immunized mice. Thus, we provide evidence supporting the adjuvant activity of PPSB in DNA vaccine against tumor.
基金support from the National Natural Science Foundation of China (No.52074330&No.52288101)Taishan Scholar Foundation of Shandong Province (No.202208832).
文摘The ionic liquid,as a new treatment agent,has been increasingly applied in oil fields due to its strong temperature resistance,good solubility and high surface activity.In this paper,we systematically discuss the action mechanism and application effect of ionic liquids in oilfield chemistry.Ionic liquids can inhibit shale hydration expansion and reduce fluid loss through adsorption and intercalation,inhibit the formation of natural gas hydrate through imidazole five-membered ring structure as a space barrier,reduce viscosity of heavy oil by breaking chemical bonds of heavy oil macromolecules and charge transfer,improve oil displacement efficiency by forming ions pairs with carboxyl groups in crude oil,demulsify by forming channels between dispersed water droplets,acidify the formation by reacting with water to produce acid,interacts with organic material through weak hydrogen bonds and extracts it from oilfield wastewater,desulphurize by inserting sulfide molecules into the“stack”structure and form liquid inclusion complex,inhibit corrosion by forming a protective film on the metal surface.Based on the above aspects,the development direction of ionic liquids is proposed.The application of ionic liquids in oilfield chemistry is still in its infancy.It is urgent to fully explore the application performance of ionic liquids in oilfield chemistry,which also provides theoretical and technical supports for efficient reservoir development.
基金supported by the National Natural Science Foundation of China(32071453,32271438,31871001 to Jingping Liu)the 1.3.5 Project for Disciplines of Excellence(ZYYC23001 to Jingping Liu,China),West China Hospital of Sichuan University.
文摘Mesenchymal stem cell(MSC)-based therapies have emerged as promising methods for regenerative medicine;however,how to precisely enhance their tissue repair effects is still a major question in the field.Circulating extracellular vesicles(EVs)from diseased states carry diverse pathological information and affect the functions of recipient cells.Based on this unique property,we report that disease-derived circulating EV(disease-EV)preconditioning is a potent strategy for precisely enhancing the tissue repair potency of MSCs in diverse disease models.Briefly,plasma EVs from lung or kidney tissue injuries were shown to contain distinctly enriched molecules and were shown to induce tissue injury-specific gene expression responses in cultured MSCs.Disease-EV preconditioning improved the performance(including proliferation,migration,and growth factor production)of MSCs through metabolic reprogramming(such as via enhanced oxidative phosphorylation and lipid metabolism)without inducing an adverse immune response.Consequently,compared with normal MSCs,disease-EV-preconditioned MSCs exhibited superior tissue repair effects(including anti-inflammatory and antiapoptotic effects)in diverse types of tissue injury(such as acute lung or kidney injury).Disease-derived EVs may serve as a type of“off-the-shelf”product due to multiple advantages,such as flexibility,stability,long-term storage,and ease of shipment and use.This study highlights the idea that disease-EV preconditioning is a robust strategy for precisely enhancing the regenerative capacity of MSC-based therapies.
文摘Graphene is a single atom thick crystal composed of carbon atoms.It is the lightest,thinnest,strongest material that conducts heat and electricity well heretofore.In terms of application,by introducing oxygen-containing groups,graphene can be well dispersed in solvents,can be chemically modified and functionalized,or connected with other electroactive substances through covalent bond or non-covalent bond to form composite materials,which is conducive to further processing and promotion.The application of graphene in oilfield chemistry started late,but developed rapidly.Graphene has played an active role in drilling fluid,cementing fluid,fracturing fluid,displacement fluid and other oilfield working fluids.It can enhance the temperature and salt resistance of working fluid and improve the effect of working fluid.In this paper,several directions of graphene applications in oilfield chemistry,such as modified graphene,graphene copolymers and graphene nanoparticles,are reviewed in detail from the synthesis methods,action mechanisms and effects of graphene and its derivatives,and the frontier cases at this stage are given.On the basis of the existing research,suggestions for the development direction of graphene materials in oilfield chemistry are given for a variety of graphene materials,aiming to provide guidance for the application of graphene in oilfield chemistry.
基金supported by Natural Science Foundation of China(Nos.81974552,81774160)Technology Agency of Sichuan Province Foundation Project(No.2019YFS0389)Scientific Research Foundation of the Science and Technology Department of Sichuan Province(No.2022YFS0417,China).
文摘Severe acute pancreatitis-associated acute lung injury(SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI;however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely,emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury,and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.
基金This research work is jointly sponsored by the National Natural Science Foundation of China(No.51776061)Young Elite Scientists Sponsorship Program of the China Association for Science and Technology(No.2017QNRC001)Fundamental Research Funds for the Central Universities.
文摘To enhance the fuel economy of a vehicle powered by a gasoline engine under road conditions,an energy flow test of a vehicle was performed experimentally under the New European Driving Cycle of cold start.The energy distributions and related influencing factors were analyzed using the test data.Results show that the effective power and thermal efficiency are mainly affected by the engine load except in the early stage of the New European Driving Cycle.Because of the retarded CA50 and longer CA10-90,the effective thermal efficiency is lower in the early phase of driving conditions.Initially,the heat transfer loss mainly comprises the loss of the heating,ventilation,and air conditioning system.The radiator then plays the major role,with its percentage affected by the engine load and decreasing under the extra-urban driving cycle.The exhaust gas loss is decided by the temperature and flow rate of the exhaust gas,while its percentage is mainly affected by the temperature of the exhaust gas.In the early phase of driving conditions,the retarded spark advance angle leads to a higher temperature of the exhaust gas and a greater exhaust gas loss.The pumping loss and its percentage are mainly determined by the engine speed under the urban driving cycle,and both decrease under the extra-urban driving cycle except at maximum vehicle speed.
基金supported by grants from the following institutions:the High-level Talent Start-up Funding of Southern Medical Universitythe National Natural Science Foundation of China(grant numbers:31700061,81971420 and 81991511)+2 种基金the Guangdong Special Support Program for Youth Science and Technology Innovation Talents(grant number:2019TQ05Y585)the National Natural Science Foundation of Guangdong(grant number:2019A1515011435)the Science and Technology Program of Guangzhou(grant number:201904010073).
文摘The maternal immune system is vital in maintaining immunotolerance to the semiallogeneic fetus for a successful pregnancy.Although studies have shown that myeloid-derived suppressor cells(MDSCs)play an important role in maintaining feto-maternal tolerance,little is known about the role of MDSCs in pregnancies with intrauterine growth retardation(IUGR).Here,we reported that the activation of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)during pregnancy was closely associated with fetal growth.In humans,class E scavenger receptor 1(SR-E1),a distinct marker for human PMN-MDSCs,was used to investigate PMN-MDSC function during pregnancy.Continuous activation of SR-E1+PMN-MDSCs was observed in all stages of pregnancy,accompanied by high cellular levels of ROS and arginase-1 activity,mediated through STAT6 signaling.However,SR-E1+PMN-MDSCs in pregnancies with IUGR showed significantly lower suppressive activity,lower arginase-1 activity and ROS levels,and decreased STAT6 phosphorylation level,which were accompanied by an increase in inflammatory factors,compared with those in normal pregnancies.Moreover,the population of SR-E1+PMN-MDSCs was negatively correlated with the adverse outcomes of newborns from pregnancies with IUGR.In mice,decreases in cell population,suppressive activity,target expression levels,and STAT6 phosphorylation levels were also observed in the pregnancies with IUGR compared with the normal pregnancies,which were rescued by the adoptive transfer of PMN-MDSCs from pregnant mice.Interestingly,the growth-promoting factors(GPFs)secreted by placental PMN-MDSCs in both humans and mice play a vital role in fetal development.These findings collectively support that PMN-MDSCs have another new role in pregnancy,which can improve adverse neonatal outcomes.
基金Natural Science Foundation of China(Grants 51904328).
文摘During the drilling process for oil and gas production,a larger number of drilling fluids invade the formation,causing severe formation damage and wellbore collapsing,which seriously hinders the efficient production of deep oil and gas.Although several plugging agents have been developed for efficient fracture sealing in recent years,the development of high-performance plugging agents with self-adaptive ability and high-temperature resistance remain a challenge.Herein,we report the synthesis of an internal rigid and external flexible plugging agent PANS by reversed-phase emulsion polymerization with nano-silica as the rigid core and poly(acrylamide-co-N-vinylpyrrolidone)as a flexible shell.The plugging agent has a median particle size of 10.5μm and can self-adapt to seal the microfractures and fractures in the formation,leading to an effective reduction in the filtration loss of bentonite water-based drilling fluid under both low temperature and low pressure(LTLP)and high temperature and high pressure(HTHP)conditions.In addition,compared with the neat nano-silica(500 nm),the sealing efficiency of PANS toward 100–120 mesh sand bed was increased by 71.4%after hot rolling at 180°C.
基金partially came from National Natural Science Foundation of China Grants (82022047 and 81972100)the National Key Research and Development Program of China Grants (2019YFA0906001)Guangdong Provincial Science and Technology Innovation Council Grant (2017B030301018,China)。
文摘Osteoporosis(OP)is a systemic skeletal disease that primarily affects the elderly population,which greatly increases the risk of fractures.Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass.Kindlin-2 specific deletion(K2KO)controlled by Adipoq-Cre mice or adipose tissue-targeting AAV(AAV-Rec2-CasRx-sgK2)significantly increases bone mass.Mechanistically,Kindlin-2 promotes peroxisome proliferator-activated receptor gamma(PPARγ)activation and downstream fatty acid binding protein 4(FABP4)expression through stabilizing fatty acid synthase(FAS),and increased FABP4 inhibits insulin expression and decreases bone mass.Kindlin-2 inhibition results in accelerated FAS degradation,decreased PPARγactivation and FABP4 expression,and therefore increased insulin expression and bone mass.Interestingly,we find that FABP4 is increased while insulin is decreased in serum of OP patients.Increased FABP4 expression through PPARγactivation by rosiglitazone reverses the high bone mass phenotype of K2KO mice.Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice.Collectively,our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.
