Two years after the coronavirus disease 2019(COVID-19)outbreak,an increasing number of patients continue to suffer from long COVID(LC),persistent symptoms,and/or delayed or long-term complications beyond the initial 4...Two years after the coronavirus disease 2019(COVID-19)outbreak,an increasing number of patients continue to suffer from long COVID(LC),persistent symptoms,and/or delayed or long-term complications beyond the initial 4 weeks from the onset of symptoms.Constant fatigue is one of the most common LC symptoms,leading to severely reduced quality of life among patients.Ginseng Radix et Rhizoma—known as the King of Herbs in traditional Chinese medicine—has shown clinical anti-fatigue effects.In this review,we summarize the underlying anti-fatigue mechanisms of Ginseng Radix et Rhizoma extracts and their bioactive compounds,with a special focus on anti-viral,immune remodeling,endocrine system regulation,and metabolism,suggesting that Ginseng Radix et Rhizoma is a potentially promising treatment for LC,especially regarding targeting fatigue.展开更多
In order to study the influence of dry methane concentration on outputs in solid oxide fuel cells (SOFCs), the output performance was obtained for dry methane of different concentrations on a Ni-ScSZ anode in solid ox...In order to study the influence of dry methane concentration on outputs in solid oxide fuel cells (SOFCs), the output performance was obtained for dry methane of different concentrations on a Ni-ScSZ anode in solid oxide fuel cells, and the anode exhaust gas was measured by online chromatography. The underlying causes of the output performance change were analyzed from the anode reactions by summarizing the anode exhaust gas regular pattern for different reactions, and analyzing the electrochemical reaction kinetics of methane with oxygen ion. As the oxygen ion concentration at the anode three-phase boundary proportionally increased with current density, the following reactions occurred for different dry methane concentrations in sequence CH4 + O2﹣ → CO + 2H2 + 2e﹣, CH4 + 2O2﹣ → CO + H2O + H2 + 4e﹣, CH4 + 3O2﹣ → CO + 2H2O + 6e﹣, CH4 + 4O2﹣ → CO2 + 2H2O + 8e﹣. With various concentrations of methane at a low current, the outlet methane continuously reduced with the increase of the current density. Meanwhile, CO and H2 exhaust gas increased with increasing current density for low concentration of methane. With methane concentrations at 3.85% and 5.66%, the cell output voltage dropped rapidly. For concentrations of 29.7% and 3.85%, the anode exhaust residual methane changed irregularly with current density and this phenomenon was associated with the dry methane that reacted on anode of the cell. The transformation of reactions, the water produced in the electrochemical reactions and the polarization in response to the change of reactions maybe induced the output voltage and power density reducing as low concentrations of dry methane were used.展开更多
Introduction: Smoking and non-smoking lung cancer have many differences in clinical feature. But those may be the result of interference due to differences in pathological type, as most smoking patients suffer squmous...Introduction: Smoking and non-smoking lung cancer have many differences in clinical feature. But those may be the result of interference due to differences in pathological type, as most smoking patients suffer squmous cell lung cancer and non-smokings tend to get adenocarcinoma. This study was conducted on the specific histological type-lung adenocarcinoma-to avoid histological bias and to reveal the true effect of smoking. Methods: A total of 2222 patients with lung adenocarcinoma confirmed by histological or cytological evidence were enrolled from January 1, 1999 to December 31, 2004. Differences in clinical features and prognosis between non-smoking and smoking patients were analyzed.Chisquare test was used for univariate comparisons. Univariate probability of survival was computed using Kaplan-Meier estimate and compared to using the log-rank test. Cox proportional hazards regression analysis was used to evaluate the risk of death. Results: There were 777 current smokers (34.96%), 197 former smokers (8.87%) and 1248 non-smoking patients (56.17%). 860 non-smoking patients (68.91%) were female, compared with 6.31% among current smokers and 4.06% among former smokers (p < 0.001). Non-smoking patients had an earlier age at diagnosis (p < 0.001) and a better response to chemotherapy (p < 0.001) compared to current smoking patients. Current smoking correlated with lower cell differentiation (p < 0.001) and worse prognosis (p = 0.0024). After multivariate analysis, smoking was identified as an independent negative prognostic factor (HR, 1.302;95% CI, 1.011 - 1.6780, p = 0.041). No difference in prognosis was observed according to smoking conditions in smoking patients. Conclusions: Significent differences exist in clinical features and prognosis between non-smoking and smoking lung adenocarcinoma patients. There is a strong evidence that non-smoking lung adenocarcinoma should be regard as different disease.展开更多
With the improvement of living standards,people pay more and more attention to the quality and safety of rice.Microbial agents are favored by the public because they can activate the nutrient supply in the soil,and re...With the improvement of living standards,people pay more and more attention to the quality and safety of rice.Microbial agents are favored by the public because they can activate the nutrient supply in the soil,and reduce the residue and application amount of chemical fertilizers and pesticides.Based on the conventional fertilization in the field,Bacillus mucilaginosus and Aspergillus niger were applied,Bacillus mucilaginosus was inoculated at four levels in the paddy soil in the cold region of Heilongjiang Province of China.The effects of different proportions of Bacillus mucilaginosus and Aspergillus niger on the number of soil microorganisms,enzyme activity,microbial biomass,soil biochemical intensity,soil nutrient content,plant nutrient content and yield were studied,and the effects on the plant nutrient content of rice and the nutrient dynamics were discussed.The results showed that a 2.62%-21.20%higher yield of rice obtained from co-application treatments compared with that of the control-blank treatment.Furthermore,the highest yield obtained(10736±65 kg/hm^(2))suggested that the optimized values for the two bacteria applied were 120×10^(11) CFU/hm^(2) for Bacillus mucilaginosus and 15×10^(11) CFU/hm^(2) for Aspergillus niger.Bacillus mucilaginosus can decompose minerals in soil,dissolve potassium and silicon,decompose apatite and release phosphorus into soil.Aspergillus niger can transform the phosphate which cannot be absorbed by plants into soluble phosphate which can be directly absorbed by plants by producing non-volatile acids.In particular,Bacillus mucilaginosus and Aspergillus niger have synergistic effect,and their combined application effect is greater than that of two bacteria alone.Co-application promoted the release of soil soluble silicon,and then increased the silicon content of plants.At the same time,soil microorganism,microbial biomass,enzyme activity and biochemical activity all increased significantly.This study provides an effective way to reduce the amount of chemical fertilizer applied in rice production in cold regions of China.展开更多
MicroRNAs(miRNAs)are involved in lymphoma progression by regulating the tumor microenvironment.Serum miR130b is overexpressed in diffuse large B-cell lymphoma(DLBCL),inducing Th17 cell alterations.To further illustrat...MicroRNAs(miRNAs)are involved in lymphoma progression by regulating the tumor microenvironment.Serum miR130b is overexpressed in diffuse large B-cell lymphoma(DLBCL),inducing Th17 cell alterations.To further illustrate its biological significance and therapeutic rationale,miR130b was detected by quantitative real-time PCR in the serum samples of 532 newly diagnosed DLBCL patients.The mechanism of miR130b on lymphoma progression and the tumor microenvironment was investigated both in vitro and in vivo.Therapeutic targeting miR130b was also evaluated,including OX40 agonistic antibody and lipid nanoparticles(LNPs)-miR130b antagomir.The results showed that serum miR130b significantly correlated with tumor miR130b and serum interleukin-17,indicating lymphoma relapse and inferior survival of DLBCL patients.MiR130b overexpression altered tumor microenvironment signaling pathways and increased Th17 cell activity.As mechanism of action,miR130b downregulated tumor OX40L expression by directly targeting IFNAR1/p-STAT1 axis,recruiting Th17 cells via OX40/OX40L interaction,thereby promoting immunosuppressive function of Th17 cells.In co-culture systems of B-lymphoma cells with immune cells,miR130b inhibited lymphoma cell autophagy,which could be counteracted by OX40 agonistic antibody and LNPs-miR130b antagomir.In murine xenograft model established with subcutaneous injection of A20 cells,both OX40 agonistic antibody and LNPs-miR130b antagomir remarkably inhibited Th17 cells and retarded miR130b-overexpressing tumor growth.In conclusion,as an oncogenic biomarker of DLBCL,miR130b was related to lymphoma progression through modulating OX40/OX40L-mediated lymphoma cell interaction with Th17 cells,attributing to B-cell lymphoma sensitivity towards OX40 agonistic antibody.Targeting miR130b using LNPs-miR130b antagomir could also be a potential immunotherapeutic strategy in treating OX40-altered lymphoid malignancies.展开更多
Rivers are critical links in the carbon and nitrogen cycle in aquatic,terrestrial,and atmospheric environments.Here riverine carbon and nitrogen exports in nine large rivers on the Tibetan Plateau—the"Water Tower of...Rivers are critical links in the carbon and nitrogen cycle in aquatic,terrestrial,and atmospheric environments.Here riverine carbon and nitrogen exports in nine large rivers on the Tibetan Plateau—the"Water Tower of Asia"—were investigated in the monsoon season from 2013 to 2015.Compared with the world average,concentrations of dissolved inorganic carbon(DIC,30.7 mg/L)were high in river basins of the plateau due to extensive topographic relief and intensive water erosion.Low concentrations of dissolved organic carbon(DOC,1.16 mg/L)were likely due to the low temperature and unproductive land vegetation environments.Average concentrations of riverine DIN(0.32 mg/L)and DON(0.35 mg/L)on the Tibetan Plateau were close to the world average.However,despite its predominantly pristine environment,discharge from agricultural activities and urban areas of the plateau has raised riverine N export.In addition,DOC/DON ratio(C/N,~6.5)in rivers of the Tibetan Plateau was much lower than the global average,indicating that dissolved organic carbon in the rivers of this region might be more bioavailable.Therefore,along with global warming and anthropogenic activities,increasing export of bioavailable riverine carbon and nitrogen from rivers of the Tibetan Plateau can be expected in the future,which will possibly influence the regional carbon and nitrogen cycle.展开更多
With the proliferation of the Internet,particularly the rise of social media,digital images have gradually become an important part of life,and trading platforms have emerged for buying and selling images.However,trad...With the proliferation of the Internet,particularly the rise of social media,digital images have gradually become an important part of life,and trading platforms have emerged for buying and selling images.However,traditional image trading service providers may disclose users’private information for profit.Additionally,many image trading platforms disregard the fairness of a transaction and the issue of copyright protection after an image is sold.This neglect harms the interests of users and affects their enthusiasm for trading.A secure way to safely transact images is needed.We proposed a copyright-preserving and fair image trading scheme based on blockchain,which combines amplifying locality-sensitive hashing with searchable symmetric encryption to achieve safe image retrieval on blockchain and ensure the credibility of the image retrieval process.Additionally,we use digital fingerprint and watermark technologies to realize the copyright protection of images and use smart contracts to achieve fair transaction processes.The experimental results show that our scheme can protect image copyrights and realize a fair trading process while ensuring efficiency.展开更多
Glutaric aciduria type I(GA-I)is an autosomal recessive genetic disorder caused by a deficiency in glutaryl-CoA dehydrogenase(GCDH).Patients who do not receive proper treatment may die from acute encephalopathic crisi...Glutaric aciduria type I(GA-I)is an autosomal recessive genetic disorder caused by a deficiency in glutaryl-CoA dehydrogenase(GCDH).Patients who do not receive proper treatment may die from acute encephalopathic crisis.Current treatments for GA-I include a low-lysine diet combined with oral supplementation of L-carnitine.A mouse model of Gcdh^(c.422_428del/c.422_428del)(Gcdh^(−/−))was generated in our laboratory using CRISPR/Cas9.Gcdh^(−/−)mice had significantly higher levels of glutaric acid(GA)in the plasma,liver,and brain than those in wild-type C57BL/6 mice.When given a high-protein diet(HPD)for two days,approximately 60%of Gcdh^(−/−)mice did not survive the metabolic stress.To evaluate whether GCDH gene replacement therapy could be used to provide sustained treatment for patients with GA-1,we prepared a recombinant adeno-associated virus(rAAV)carrying a human GCDH expression cassette and injected it into Gcdh^(−/−)neonates for a proof-of-concept(PoC)study.Our study demonstrated that delivering rAAV to the central nervous system(CNS),but not the peripheral system,significantly increased the survival rate under HPD exposure.Our study also demonstrated that rAAVPHP.eB mediated a higher efficiency than that of rAAV9 in increasing the survival rate.Surviving mice showed dose-dependent GCDH protein expression in the CNS and downregulation of GA levels.Our study demonstrated that AAV-based gene replacement therapy was effective for GA-I treatment and provided a feasible solution for this unmet medical need.展开更多
基金supported by National Natural Science Foundation of China(61533013,61273144)Scientific Technology Research and Development Plan Project of Tangshan(13130298B)Scientific Technology Research and Development Plan Project of Hebei(z2014070)
基金funded by the Science&Technology Development Fund of the Tianjin Education Commission for Higher Education(2018KJ010)。
文摘Two years after the coronavirus disease 2019(COVID-19)outbreak,an increasing number of patients continue to suffer from long COVID(LC),persistent symptoms,and/or delayed or long-term complications beyond the initial 4 weeks from the onset of symptoms.Constant fatigue is one of the most common LC symptoms,leading to severely reduced quality of life among patients.Ginseng Radix et Rhizoma—known as the King of Herbs in traditional Chinese medicine—has shown clinical anti-fatigue effects.In this review,we summarize the underlying anti-fatigue mechanisms of Ginseng Radix et Rhizoma extracts and their bioactive compounds,with a special focus on anti-viral,immune remodeling,endocrine system regulation,and metabolism,suggesting that Ginseng Radix et Rhizoma is a potentially promising treatment for LC,especially regarding targeting fatigue.
文摘In order to study the influence of dry methane concentration on outputs in solid oxide fuel cells (SOFCs), the output performance was obtained for dry methane of different concentrations on a Ni-ScSZ anode in solid oxide fuel cells, and the anode exhaust gas was measured by online chromatography. The underlying causes of the output performance change were analyzed from the anode reactions by summarizing the anode exhaust gas regular pattern for different reactions, and analyzing the electrochemical reaction kinetics of methane with oxygen ion. As the oxygen ion concentration at the anode three-phase boundary proportionally increased with current density, the following reactions occurred for different dry methane concentrations in sequence CH4 + O2﹣ → CO + 2H2 + 2e﹣, CH4 + 2O2﹣ → CO + H2O + H2 + 4e﹣, CH4 + 3O2﹣ → CO + 2H2O + 6e﹣, CH4 + 4O2﹣ → CO2 + 2H2O + 8e﹣. With various concentrations of methane at a low current, the outlet methane continuously reduced with the increase of the current density. Meanwhile, CO and H2 exhaust gas increased with increasing current density for low concentration of methane. With methane concentrations at 3.85% and 5.66%, the cell output voltage dropped rapidly. For concentrations of 29.7% and 3.85%, the anode exhaust residual methane changed irregularly with current density and this phenomenon was associated with the dry methane that reacted on anode of the cell. The transformation of reactions, the water produced in the electrochemical reactions and the polarization in response to the change of reactions maybe induced the output voltage and power density reducing as low concentrations of dry methane were used.
文摘Introduction: Smoking and non-smoking lung cancer have many differences in clinical feature. But those may be the result of interference due to differences in pathological type, as most smoking patients suffer squmous cell lung cancer and non-smokings tend to get adenocarcinoma. This study was conducted on the specific histological type-lung adenocarcinoma-to avoid histological bias and to reveal the true effect of smoking. Methods: A total of 2222 patients with lung adenocarcinoma confirmed by histological or cytological evidence were enrolled from January 1, 1999 to December 31, 2004. Differences in clinical features and prognosis between non-smoking and smoking patients were analyzed.Chisquare test was used for univariate comparisons. Univariate probability of survival was computed using Kaplan-Meier estimate and compared to using the log-rank test. Cox proportional hazards regression analysis was used to evaluate the risk of death. Results: There were 777 current smokers (34.96%), 197 former smokers (8.87%) and 1248 non-smoking patients (56.17%). 860 non-smoking patients (68.91%) were female, compared with 6.31% among current smokers and 4.06% among former smokers (p < 0.001). Non-smoking patients had an earlier age at diagnosis (p < 0.001) and a better response to chemotherapy (p < 0.001) compared to current smoking patients. Current smoking correlated with lower cell differentiation (p < 0.001) and worse prognosis (p = 0.0024). After multivariate analysis, smoking was identified as an independent negative prognostic factor (HR, 1.302;95% CI, 1.011 - 1.6780, p = 0.041). No difference in prognosis was observed according to smoking conditions in smoking patients. Conclusions: Significent differences exist in clinical features and prognosis between non-smoking and smoking lung adenocarcinoma patients. There is a strong evidence that non-smoking lung adenocarcinoma should be regard as different disease.
基金This work was supported by Research Science Foundation in Technology Innovation of Harbin(Grant No.RC2013XK002015).
文摘With the improvement of living standards,people pay more and more attention to the quality and safety of rice.Microbial agents are favored by the public because they can activate the nutrient supply in the soil,and reduce the residue and application amount of chemical fertilizers and pesticides.Based on the conventional fertilization in the field,Bacillus mucilaginosus and Aspergillus niger were applied,Bacillus mucilaginosus was inoculated at four levels in the paddy soil in the cold region of Heilongjiang Province of China.The effects of different proportions of Bacillus mucilaginosus and Aspergillus niger on the number of soil microorganisms,enzyme activity,microbial biomass,soil biochemical intensity,soil nutrient content,plant nutrient content and yield were studied,and the effects on the plant nutrient content of rice and the nutrient dynamics were discussed.The results showed that a 2.62%-21.20%higher yield of rice obtained from co-application treatments compared with that of the control-blank treatment.Furthermore,the highest yield obtained(10736±65 kg/hm^(2))suggested that the optimized values for the two bacteria applied were 120×10^(11) CFU/hm^(2) for Bacillus mucilaginosus and 15×10^(11) CFU/hm^(2) for Aspergillus niger.Bacillus mucilaginosus can decompose minerals in soil,dissolve potassium and silicon,decompose apatite and release phosphorus into soil.Aspergillus niger can transform the phosphate which cannot be absorbed by plants into soluble phosphate which can be directly absorbed by plants by producing non-volatile acids.In particular,Bacillus mucilaginosus and Aspergillus niger have synergistic effect,and their combined application effect is greater than that of two bacteria alone.Co-application promoted the release of soil soluble silicon,and then increased the silicon content of plants.At the same time,soil microorganism,microbial biomass,enzyme activity and biochemical activity all increased significantly.This study provides an effective way to reduce the amount of chemical fertilizer applied in rice production in cold regions of China.
基金the National Natural Science Foundation of China(81830007,82130004,81900193,and 21871180)Chang Jiang Scholars Program,Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(20152206 and 20152208)+5 种基金Shanghai Sailing Program(19YF1430900)Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1032B)Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine(DLY201601)Multicenter Hematology-Oncology Programs Evaluation System(M-HOPES)Collaborative Innovation Center of Systems Biomedicinethe Samuel Waxman Cancer Research Foundation.
文摘MicroRNAs(miRNAs)are involved in lymphoma progression by regulating the tumor microenvironment.Serum miR130b is overexpressed in diffuse large B-cell lymphoma(DLBCL),inducing Th17 cell alterations.To further illustrate its biological significance and therapeutic rationale,miR130b was detected by quantitative real-time PCR in the serum samples of 532 newly diagnosed DLBCL patients.The mechanism of miR130b on lymphoma progression and the tumor microenvironment was investigated both in vitro and in vivo.Therapeutic targeting miR130b was also evaluated,including OX40 agonistic antibody and lipid nanoparticles(LNPs)-miR130b antagomir.The results showed that serum miR130b significantly correlated with tumor miR130b and serum interleukin-17,indicating lymphoma relapse and inferior survival of DLBCL patients.MiR130b overexpression altered tumor microenvironment signaling pathways and increased Th17 cell activity.As mechanism of action,miR130b downregulated tumor OX40L expression by directly targeting IFNAR1/p-STAT1 axis,recruiting Th17 cells via OX40/OX40L interaction,thereby promoting immunosuppressive function of Th17 cells.In co-culture systems of B-lymphoma cells with immune cells,miR130b inhibited lymphoma cell autophagy,which could be counteracted by OX40 agonistic antibody and LNPs-miR130b antagomir.In murine xenograft model established with subcutaneous injection of A20 cells,both OX40 agonistic antibody and LNPs-miR130b antagomir remarkably inhibited Th17 cells and retarded miR130b-overexpressing tumor growth.In conclusion,as an oncogenic biomarker of DLBCL,miR130b was related to lymphoma progression through modulating OX40/OX40L-mediated lymphoma cell interaction with Th17 cells,attributing to B-cell lymphoma sensitivity towards OX40 agonistic antibody.Targeting miR130b using LNPs-miR130b antagomir could also be a potential immunotherapeutic strategy in treating OX40-altered lymphoid malignancies.
基金supported by the National Natural Science Foundation of China (Nos.41675130, 41271015, 41225002)the Academy of Finland (decision number: 268170)the State Key Laboratory of Cryospheric Science (SKLCS-ZZ-2008-01 and SKLCS-OP-2014-05)
文摘Rivers are critical links in the carbon and nitrogen cycle in aquatic,terrestrial,and atmospheric environments.Here riverine carbon and nitrogen exports in nine large rivers on the Tibetan Plateau—the"Water Tower of Asia"—were investigated in the monsoon season from 2013 to 2015.Compared with the world average,concentrations of dissolved inorganic carbon(DIC,30.7 mg/L)were high in river basins of the plateau due to extensive topographic relief and intensive water erosion.Low concentrations of dissolved organic carbon(DOC,1.16 mg/L)were likely due to the low temperature and unproductive land vegetation environments.Average concentrations of riverine DIN(0.32 mg/L)and DON(0.35 mg/L)on the Tibetan Plateau were close to the world average.However,despite its predominantly pristine environment,discharge from agricultural activities and urban areas of the plateau has raised riverine N export.In addition,DOC/DON ratio(C/N,~6.5)in rivers of the Tibetan Plateau was much lower than the global average,indicating that dissolved organic carbon in the rivers of this region might be more bioavailable.Therefore,along with global warming and anthropogenic activities,increasing export of bioavailable riverine carbon and nitrogen from rivers of the Tibetan Plateau can be expected in the future,which will possibly influence the regional carbon and nitrogen cycle.
基金supported by the National Natural Science Foundation of China(Nos.62062016,U21A20474)Guangxi Natural Science Foundation(No.2019JJA170060)+1 种基金Jiangsu Provincial Key Laboratory of Network and Information Security(No.BM2003201)Guangxi Science and Technology project(Nos.GuikeAA22067070,GuikeAD21220114).
文摘With the proliferation of the Internet,particularly the rise of social media,digital images have gradually become an important part of life,and trading platforms have emerged for buying and selling images.However,traditional image trading service providers may disclose users’private information for profit.Additionally,many image trading platforms disregard the fairness of a transaction and the issue of copyright protection after an image is sold.This neglect harms the interests of users and affects their enthusiasm for trading.A secure way to safely transact images is needed.We proposed a copyright-preserving and fair image trading scheme based on blockchain,which combines amplifying locality-sensitive hashing with searchable symmetric encryption to achieve safe image retrieval on blockchain and ensure the credibility of the image retrieval process.Additionally,we use digital fingerprint and watermark technologies to realize the copyright protection of images and use smart contracts to achieve fair transaction processes.The experimental results show that our scheme can protect image copyrights and realize a fair trading process while ensuring efficiency.
基金the National Key Research and Development Program(2019YFA0110800 and 2020YFA0707900 to W.L.,and 2018YFA0108400 and 2019YFA0903800 to Q.Z.)Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030403 to W.L.)+1 种基金National Natural Science Foundation of China(31621004 to Q.Z.and W.L.)CAS Project for Young Scientists in Basic Research(YSBR-012 to W.L.).
文摘Glutaric aciduria type I(GA-I)is an autosomal recessive genetic disorder caused by a deficiency in glutaryl-CoA dehydrogenase(GCDH).Patients who do not receive proper treatment may die from acute encephalopathic crisis.Current treatments for GA-I include a low-lysine diet combined with oral supplementation of L-carnitine.A mouse model of Gcdh^(c.422_428del/c.422_428del)(Gcdh^(−/−))was generated in our laboratory using CRISPR/Cas9.Gcdh^(−/−)mice had significantly higher levels of glutaric acid(GA)in the plasma,liver,and brain than those in wild-type C57BL/6 mice.When given a high-protein diet(HPD)for two days,approximately 60%of Gcdh^(−/−)mice did not survive the metabolic stress.To evaluate whether GCDH gene replacement therapy could be used to provide sustained treatment for patients with GA-1,we prepared a recombinant adeno-associated virus(rAAV)carrying a human GCDH expression cassette and injected it into Gcdh^(−/−)neonates for a proof-of-concept(PoC)study.Our study demonstrated that delivering rAAV to the central nervous system(CNS),but not the peripheral system,significantly increased the survival rate under HPD exposure.Our study also demonstrated that rAAVPHP.eB mediated a higher efficiency than that of rAAV9 in increasing the survival rate.Surviving mice showed dose-dependent GCDH protein expression in the CNS and downregulation of GA levels.Our study demonstrated that AAV-based gene replacement therapy was effective for GA-I treatment and provided a feasible solution for this unmet medical need.