Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes.However,therapeutic decision-making is relatively complex for epilepsies associated with channelopathy.Therefore,in the pres...Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes.However,therapeutic decision-making is relatively complex for epilepsies associated with channelopathy.Therefore,in the present study,we used a patient-derived organoid model with a novel SCN2A mutation(p.E512K)to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds.The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation.Immunofluorescence staining of patient-derived cortical organoids(COs)displayed normal neurodevelopment.Multielectrode array(MEA)recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts.Moreover,the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine.Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.展开更多
(E)ω-formylcamphene was synthesized fromα-pinene,the main component of turpentine,and then reacted with thiosemicarbazide to obtain(E)ω-formylcamphene thiosemicarbazide 3,which was reacted with 14α-bromoace-tophen...(E)ω-formylcamphene was synthesized fromα-pinene,the main component of turpentine,and then reacted with thiosemicarbazide to obtain(E)ω-formylcamphene thiosemicarbazide 3,which was reacted with 14α-bromoace-tophenone compounds to obtain 14(E)ω-formylcamphene thiazole hydrazone compounds 5a–5n;the yields were all above 80%.The structures of the target compounds were characterized by IR,^(1)H-NMR,^(13)C-NMR,and HR-MS analyses.Then,500,250,125,62.5,and 31.25 mg/L drug solutions were prepared.Free radical scavenging experi-ments of 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2-bis(3-ethyl-benzothiazole-6-sulfonic acid)diammonium salt(ABTS)were carried out with Trolox and L-ascorbic acid as the control samples.The scavenging rates of 14 compounds for DPPH and ABTS free radicals were obtained;the IC_(50) values of scavenging free radicals were fitted using SPSS software.The results show that 14(E)ω-formylcamphene-based thiazole hydrazone compounds exhibited good scavenging effects on the two free radicals,especially when the concentration of the drug solution was 125 and 62.5 mg/L;most compounds exceeded the scavenging efficiency of Trolox and L-ascorbic acid.展开更多
Nitrite-and nitrate-coupled anaerobic oxidation of methane(AOM),mediated by Candidatus Methylomirabilis-like bacteria and Methanoperedens-like archaea,respectively,are two recent additions of freshwater carbon and nit...Nitrite-and nitrate-coupled anaerobic oxidation of methane(AOM),mediated by Candidatus Methylomirabilis-like bacteria and Methanoperedens-like archaea,respectively,are two recent additions of freshwater carbon and nitrogen cycles.However,the quantitative roles of the two AOM processes in CH_(4)emission reduction in lakes have not yet been characterized.Here,we explored vertical(0–10,10–20,and 20–30 cm)variation in nitrite-and nitrate-coupled AOM activity,as well as the abundance and community structure of Methylomirabilis-and Methanoperedens-like methanotrophs in freshwater lake sediment.The potential rates of nitrite-and nitrate-coupled AOM quantified via^(13)CH_(4)isotopic experiments were 0.41–3.84 and 0.32–3.88 nmol CH_(4)/(g·d),respectively.The rates of AOM exhibited significant and consistent depth-related variation across different sampling sites,with both peaking in the 10–20 cm layer.The abundance of Methylomirabilis-like bacteria and Methanoperedens-like archaea quantified via quantitative PCR was 3.34×10^(5)–9.17×10^(6)and 1.27×10^(6)–9.46×10^(6)copies/g,respectively.There was no consistent depth-related variation in the abundance of bacteria or archaea.The community composition of both Methylomirabilis-and Methanoperedens-like methanotrophs remained relatively stable along the sediment profile,while the composition significantly changed across sampling sites.Sediment pH and the content of NH4+and organic carbon were key variables influencing the community structure of Methylomirabilis-and Methanoperedens-like methanotrophs.Overall,we characterized vertical variation in nitrite-and nitrate-coupled AOM processes in lake sediment,which helps quantify their role in CH_(4)consumption in freshwater aquatic ecosystems.展开更多
Nitrite-dependent anaerobic methane oxidation (n-damo), performed by the bacteria associated with Candidatus Methylomirabilis oxyfera, acts as a novel methane sink in coastal wetlands. Conversion of coastal wetlands i...Nitrite-dependent anaerobic methane oxidation (n-damo), performed by the bacteria associated with Candidatus Methylomirabilis oxyfera, acts as a novel methane sink in coastal wetlands. Conversion of coastal wetlands into paddy fields is a common land-use change that has profound effects on methane emissions, but its impact on n-damo process is nearly unknown. Our study adopted a space-for-time substitution method to compare n-damo activity and community of Methylomirabilis-like bacteria between natural vegetation covered by Phragmites australis, Kandelia candek, or Bruguiera sexangula and adjacent converted paddy fields in six China’s coastal wetlands. Generalized linear mixed model indicated that the activity of n-damo significantly increased by 43.6% and 165.8% after conversion of K. candek and B. sexangula wetlands into rice paddies, respectively, while the activity exhibited no significant change after conversion of P. australis wetlands. Furthermore, the abundance of Methylomirabilis-like bacteria significantly increased by 90.2%, 210.0%, and 110.1% following the conversion in wetlands covered by K. candek, B. sexangula, and P. australis, respectively. Principal co-ordinates analysis revealed significant changes in community structure of Methylomirabilis-like bacteria among vegetation types, with K. candek and B. sexangula showing a greater divergence than P. australis when compared to respective paddy fields. Path analysis indicated that land conversion resulted in changes in soil moisture content, organic carbon content, bulk density, and salinity and further affected the abundance of Methylomirabilis-like bacteria and ultimately n-damo activity. Overall, this is the first study to reveal the impact of conversion of coastal wetlands into paddy fields on n-damo activity and Methylomirabilis-like bacteria, and the impact was closely associated with the original native plant types. The results can enhance our understanding of the microbial-driven mechanisms of the impact of land conversion on methane emissions.展开更多
Background and Aims:The prognosis of hepatocellular carcinoma(HCC)is extremely poor;therefore,there is an urgent need for novel prognostic molecular biomarkers of HCC.The current investigation utilized circular(circ)R...Background and Aims:The prognosis of hepatocellular carcinoma(HCC)is extremely poor;therefore,there is an urgent need for novel prognostic molecular biomarkers of HCC.The current investigation utilized circular(circ)RNA-associated competing endogenous(ce)RNAs analysis in order to identify significant prognostic biomarkers of HCC.Methods:CircRNAs and mRNAs that were differentially expressed between normal and HCC tissues were identi-fied.Their respective functions were predicted with Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.A nomogram was used for model verification.Results:A ceRNA network composed of differentially expressed circRNAs and mRNAs was con-structed.Significant hub nodes in the ceRNA network were hsa_circ_0004662,hsa_circ_0005735,hsa_circ_0006990,hsa_circ_0018403 and hsa_circ_0100609.By using this in-formation,a prognostic risk assessment tool was developed based on the expressions of seven genes(PLOD2,TARS,RNF19B,CCT2,RAN,C5orf30 and MCM10).Furthermore,multivariate Cox regression analysis revealed risk and T-stage parameters as independent prognostic factors.The nomograms that were constructed from risk and T-stage groups were used to further assess the prediction of HCC patient survival rates.The nomogram,which consisted of risk and T-stage scores assessment models,was found to be an independent factor for predicting prognosis of HCC.Conclusions:Five circRNAs,including hsa_circ_0004662,hsa_circ_0005735,hsa_circ_0006990,hsa_circ_0018403 and hsa_circ_0100609,that may play key roles in the pro-gression of HCC were identified.Seven gene signatures were identified,which were associated with the aforemen-tioned circRNAs,including PLOD2,TARS,RNF19B,CCT2,RAN,C5orf30 and MCM10,all of which were significant genes involved in the pathophysiology of HCC.These genes may be used as a prognosticating tool in HCC patients.展开更多
Dear Editor,Polyene macrolides are a group of natural products with potent antifungal activity (Caffrey et al., 2016). Candicidin/FR-008, a potent broad-spectrum anti-fungal agent, is produced by several Streptomycete...Dear Editor,Polyene macrolides are a group of natural products with potent antifungal activity (Caffrey et al., 2016). Candicidin/FR-008, a potent broad-spectrum anti-fungal agent, is produced by several Streptomycetes, including Streptomycetes sp. strain FR-008 (Chen et al., 2003), S. griseus 3570(Campelo and Gil, 2002) and S. albus J1074 (Olano et al.,2014). Due to its medical importance, considerable effort has been applied to elucidate its biosynthetic pathway and identify key regulatory genes (Chen et al., 2003;Zhang et al.,2015).展开更多
Despite the remarkable success of immune checkpoint inhibitors(ICIs),primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment(TME).Oncolytic vir...Despite the remarkable success of immune checkpoint inhibitors(ICIs),primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment(TME).Oncolytic viruses(OVs)can overcome the immunosuppressive TME and promote systemic antitumor immunity in hosts.Engineered OVs armed with ICIs would likely have improved effectiveness as a cancer therapy.According to the diverse immune cell landscapes among different types of tumors,we rationally and precisely generated three recombinant oncolytic adenoviruses(OAds):OAd-SIRPα-Fc,OAd-Siglec10-Fc and OAd-TIGIT-Fc.These viruses were designed to locally deliver SIRPα-Fc,Siglec10-Fc or TIGIT-Fc fusion proteins recognizing CD47,CD24 or CD155,respectively,in the TME to achieve enhanced antitumor effects.Our results suggested that OAd-SIRPα-Fc and OAd-Siglec10-Fc both showed outstanding efficacy in tumor suppression of macrophage-dominated tumors,while OAd-TIGIT-Fc showed the best antitumor immunity in CD8+T-cell-dominated tumors.Importantly,the recombinant OAds activated an inflammatory immune response and generated long-term antitumor memory.In addition,the combination of OAd-Siglec10-Fc with anti-PD-1 significantly enhanced the antitumor effect in a 4T1 tumor model by remodeling the TME.In summary,rationally designed OAds expressing ICIs tailored to the immune cell landscape in the TME can precisely achieve tumor-specific immunotherapy of cancer.展开更多
With the continuous improvement of supercomputer performance and the integration of artificial intelligence with traditional scientific computing,the scale of applications is gradually increasing,from millions to tens...With the continuous improvement of supercomputer performance and the integration of artificial intelligence with traditional scientific computing,the scale of applications is gradually increasing,from millions to tens of millions of computing cores,which raises great challenges to achieve high scalability and efficiency of parallel applications on super-large-scale systems.Taking the Sunway exascale prototype system as an example,in this paper we first analyze the challenges of high scalability and high efficiency for parallel applications in the exascale era.To overcome these challenges,the optimization technologies used in the parallel supporting environment software on the Sunway exascale prototype system are highlighted,including the parallel operating system,input/output(I/O)optimization technology,ultra-large-scale parallel debugging technology,10-million-core parallel algorithm,and mixed-precision method.Parallel operating systems and I/O optimization technology mainly support largescale system scaling,while the ultra-large-scale parallel debugging technology,10-million-core parallel algorithm,and mixed-precision method mainly enhance the efficiency of large-scale applications.Finally,the contributions to various applications running on the Sunway exascale prototype system are introduced,verifying the effectiveness of the parallel supporting environment design.展开更多
oluntary contribution has become the only source of donor lungs in China since 2015.To elaborate the outcomes of patients awaiting lung transplantation(LTx)after the implementation of donation after brain death,we per...oluntary contribution has become the only source of donor lungs in China since 2015.To elaborate the outcomes of patients awaiting lung transplantation(LTx)after the implementation of donation after brain death,we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1,2015 to January 1,2021.A total of 180 patients were enrolled in the study.The median waiting time was 1.25 months.Interstitial lung disease(ILD)(103/180,57.2%)and chronic obstructive pulmonary disease(COPD)(56/180,31.1%)were the most common diseases in our study population.The mean pulmonary artery pressure(mPAP)of patients in the died-waiting group was higher than that of the survivors(53.29+21.71 mmHg vs.42.11+18.58 mmHg,P-0.002).The mortality of patients with ILD(34/103,33.00%)was nearly twice that of patients with COPD(10/56,17.86%)while awaiting LTx(P-0.041).In the died-waiting group,patients with ILD had a shorter median waiting time than patients with COPD after being listed(0.865 months vs.4.720 months,P-0.030).ILD as primary disease and mPAP>35 mmHg were two significant independent risk factors for waitlist mortality,with hazard ratios(HR)of 3.483(95%CI 1.311-9.111;P-0.011)and 3.500(95%CI 1.435-8.536;P=0.006).Hence,LTx is more urgently needed in patients with ILD and pulmonary hypertension.展开更多
基金supported by the National Key R&D Program of China(2022YFC2503802)the National Natural Science Foundation of China(82271499 and 32450530)+1 种基金the Joint Project of the Yangtze River Delta Science and Technology Innovation Community(2024CSJZN00600)the National Key Research and Development Program of China(2024YFA1108000).
文摘Mutations in ion channel genes have long been implicated in a spectrum of epilepsy syndromes.However,therapeutic decision-making is relatively complex for epilepsies associated with channelopathy.Therefore,in the present study,we used a patient-derived organoid model with a novel SCN2A mutation(p.E512K)to investigate the potential of utilizing such a model as a platform for preclinical testing of anti-seizure compounds.The electrophysiological properties of the variant Nav1.2 exhibited gain-of-function effects with increased current amplitude and premature activation.Immunofluorescence staining of patient-derived cortical organoids(COs)displayed normal neurodevelopment.Multielectrode array(MEA)recordings of patient-derived COs showed hyperexcitability with increased spiking and remarkable network bursts.Moreover,the application of patient-derived COs for preclinical drug testing using the MEA showed that they exhibit differential responses to various anti-seizure drugs and respond well to carbamazepine.Our results demonstrate that the individualized organoids have the potential to serve as a platform for preclinical pharmacological assessment.
基金funded by the National Natural Science Foundation(No.31960295)Jiangxi Province Academic and Technical Leaders Training Program Leading Talents Project(20204BCJ22022)Special Funding for Major Scientific and Technological Research and Development in Jiangxi Province(20203ABC28W016).
文摘(E)ω-formylcamphene was synthesized fromα-pinene,the main component of turpentine,and then reacted with thiosemicarbazide to obtain(E)ω-formylcamphene thiosemicarbazide 3,which was reacted with 14α-bromoace-tophenone compounds to obtain 14(E)ω-formylcamphene thiazole hydrazone compounds 5a–5n;the yields were all above 80%.The structures of the target compounds were characterized by IR,^(1)H-NMR,^(13)C-NMR,and HR-MS analyses.Then,500,250,125,62.5,and 31.25 mg/L drug solutions were prepared.Free radical scavenging experi-ments of 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2-bis(3-ethyl-benzothiazole-6-sulfonic acid)diammonium salt(ABTS)were carried out with Trolox and L-ascorbic acid as the control samples.The scavenging rates of 14 compounds for DPPH and ABTS free radicals were obtained;the IC_(50) values of scavenging free radicals were fitted using SPSS software.The results show that 14(E)ω-formylcamphene-based thiazole hydrazone compounds exhibited good scavenging effects on the two free radicals,especially when the concentration of the drug solution was 125 and 62.5 mg/L;most compounds exceeded the scavenging efficiency of Trolox and L-ascorbic acid.
基金supported by the National Natural Science Foundation of China(No.42377116)the R&D Foundation of Jiangsu Province,China(No.BK20220021)the 333 High-Level Talents Training Project of Jiangsu Province,China(No.BRA2022023).
文摘Nitrite-and nitrate-coupled anaerobic oxidation of methane(AOM),mediated by Candidatus Methylomirabilis-like bacteria and Methanoperedens-like archaea,respectively,are two recent additions of freshwater carbon and nitrogen cycles.However,the quantitative roles of the two AOM processes in CH_(4)emission reduction in lakes have not yet been characterized.Here,we explored vertical(0–10,10–20,and 20–30 cm)variation in nitrite-and nitrate-coupled AOM activity,as well as the abundance and community structure of Methylomirabilis-and Methanoperedens-like methanotrophs in freshwater lake sediment.The potential rates of nitrite-and nitrate-coupled AOM quantified via^(13)CH_(4)isotopic experiments were 0.41–3.84 and 0.32–3.88 nmol CH_(4)/(g·d),respectively.The rates of AOM exhibited significant and consistent depth-related variation across different sampling sites,with both peaking in the 10–20 cm layer.The abundance of Methylomirabilis-like bacteria and Methanoperedens-like archaea quantified via quantitative PCR was 3.34×10^(5)–9.17×10^(6)and 1.27×10^(6)–9.46×10^(6)copies/g,respectively.There was no consistent depth-related variation in the abundance of bacteria or archaea.The community composition of both Methylomirabilis-and Methanoperedens-like methanotrophs remained relatively stable along the sediment profile,while the composition significantly changed across sampling sites.Sediment pH and the content of NH4+and organic carbon were key variables influencing the community structure of Methylomirabilis-and Methanoperedens-like methanotrophs.Overall,we characterized vertical variation in nitrite-and nitrate-coupled AOM processes in lake sediment,which helps quantify their role in CH_(4)consumption in freshwater aquatic ecosystems.
基金supported by the National Natural Science Foundation of China(Grant Nos.41977037,42377116,and 42077086)the 333 High-level Talents Training Project of Jiangsu Province(Grant No.BRA2022023)Fujian Natural Science Foundation(Grant No.2021J06019).
文摘Nitrite-dependent anaerobic methane oxidation (n-damo), performed by the bacteria associated with Candidatus Methylomirabilis oxyfera, acts as a novel methane sink in coastal wetlands. Conversion of coastal wetlands into paddy fields is a common land-use change that has profound effects on methane emissions, but its impact on n-damo process is nearly unknown. Our study adopted a space-for-time substitution method to compare n-damo activity and community of Methylomirabilis-like bacteria between natural vegetation covered by Phragmites australis, Kandelia candek, or Bruguiera sexangula and adjacent converted paddy fields in six China’s coastal wetlands. Generalized linear mixed model indicated that the activity of n-damo significantly increased by 43.6% and 165.8% after conversion of K. candek and B. sexangula wetlands into rice paddies, respectively, while the activity exhibited no significant change after conversion of P. australis wetlands. Furthermore, the abundance of Methylomirabilis-like bacteria significantly increased by 90.2%, 210.0%, and 110.1% following the conversion in wetlands covered by K. candek, B. sexangula, and P. australis, respectively. Principal co-ordinates analysis revealed significant changes in community structure of Methylomirabilis-like bacteria among vegetation types, with K. candek and B. sexangula showing a greater divergence than P. australis when compared to respective paddy fields. Path analysis indicated that land conversion resulted in changes in soil moisture content, organic carbon content, bulk density, and salinity and further affected the abundance of Methylomirabilis-like bacteria and ultimately n-damo activity. Overall, this is the first study to reveal the impact of conversion of coastal wetlands into paddy fields on n-damo activity and Methylomirabilis-like bacteria, and the impact was closely associated with the original native plant types. The results can enhance our understanding of the microbial-driven mechanisms of the impact of land conversion on methane emissions.
文摘Background and Aims:The prognosis of hepatocellular carcinoma(HCC)is extremely poor;therefore,there is an urgent need for novel prognostic molecular biomarkers of HCC.The current investigation utilized circular(circ)RNA-associated competing endogenous(ce)RNAs analysis in order to identify significant prognostic biomarkers of HCC.Methods:CircRNAs and mRNAs that were differentially expressed between normal and HCC tissues were identi-fied.Their respective functions were predicted with Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.A nomogram was used for model verification.Results:A ceRNA network composed of differentially expressed circRNAs and mRNAs was con-structed.Significant hub nodes in the ceRNA network were hsa_circ_0004662,hsa_circ_0005735,hsa_circ_0006990,hsa_circ_0018403 and hsa_circ_0100609.By using this in-formation,a prognostic risk assessment tool was developed based on the expressions of seven genes(PLOD2,TARS,RNF19B,CCT2,RAN,C5orf30 and MCM10).Furthermore,multivariate Cox regression analysis revealed risk and T-stage parameters as independent prognostic factors.The nomograms that were constructed from risk and T-stage groups were used to further assess the prediction of HCC patient survival rates.The nomogram,which consisted of risk and T-stage scores assessment models,was found to be an independent factor for predicting prognosis of HCC.Conclusions:Five circRNAs,including hsa_circ_0004662,hsa_circ_0005735,hsa_circ_0006990,hsa_circ_0018403 and hsa_circ_0100609,that may play key roles in the pro-gression of HCC were identified.Seven gene signatures were identified,which were associated with the aforemen-tioned circRNAs,including PLOD2,TARS,RNF19B,CCT2,RAN,C5orf30 and MCM10,all of which were significant genes involved in the pathophysiology of HCC.These genes may be used as a prognosticating tool in HCC patients.
基金supported by the National Natural Science Foundation of China(31670050,31100069)the Fundamental Research Funds for the Central Universities(XDJK2017B011)。
文摘Dear Editor,Polyene macrolides are a group of natural products with potent antifungal activity (Caffrey et al., 2016). Candicidin/FR-008, a potent broad-spectrum anti-fungal agent, is produced by several Streptomycetes, including Streptomycetes sp. strain FR-008 (Chen et al., 2003), S. griseus 3570(Campelo and Gil, 2002) and S. albus J1074 (Olano et al.,2014). Due to its medical importance, considerable effort has been applied to elucidate its biosynthetic pathway and identify key regulatory genes (Chen et al., 2003;Zhang et al.,2015).
基金funded by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09201018-013)by Natural Science Foundation Project of Sichuan(No.2022NSFSC0848)+1 种基金as well as supported by the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD18007)The Frontiers Medical Center,Tianfu Jincheng Laboratory Foundation(TFJC202310005).
文摘Despite the remarkable success of immune checkpoint inhibitors(ICIs),primary resistance to ICIs causes only subsets of patients to achieve durable responses due to the complex tumor microenvironment(TME).Oncolytic viruses(OVs)can overcome the immunosuppressive TME and promote systemic antitumor immunity in hosts.Engineered OVs armed with ICIs would likely have improved effectiveness as a cancer therapy.According to the diverse immune cell landscapes among different types of tumors,we rationally and precisely generated three recombinant oncolytic adenoviruses(OAds):OAd-SIRPα-Fc,OAd-Siglec10-Fc and OAd-TIGIT-Fc.These viruses were designed to locally deliver SIRPα-Fc,Siglec10-Fc or TIGIT-Fc fusion proteins recognizing CD47,CD24 or CD155,respectively,in the TME to achieve enhanced antitumor effects.Our results suggested that OAd-SIRPα-Fc and OAd-Siglec10-Fc both showed outstanding efficacy in tumor suppression of macrophage-dominated tumors,while OAd-TIGIT-Fc showed the best antitumor immunity in CD8+T-cell-dominated tumors.Importantly,the recombinant OAds activated an inflammatory immune response and generated long-term antitumor memory.In addition,the combination of OAd-Siglec10-Fc with anti-PD-1 significantly enhanced the antitumor effect in a 4T1 tumor model by remodeling the TME.In summary,rationally designed OAds expressing ICIs tailored to the immune cell landscape in the TME can precisely achieve tumor-specific immunotherapy of cancer.
基金Project supported by the Key R&D Program of Zhejiang Province,China(No.2022C01250)the National Key R&D Program of China(No.2019YFA0709402)。
文摘With the continuous improvement of supercomputer performance and the integration of artificial intelligence with traditional scientific computing,the scale of applications is gradually increasing,from millions to tens of millions of computing cores,which raises great challenges to achieve high scalability and efficiency of parallel applications on super-large-scale systems.Taking the Sunway exascale prototype system as an example,in this paper we first analyze the challenges of high scalability and high efficiency for parallel applications in the exascale era.To overcome these challenges,the optimization technologies used in the parallel supporting environment software on the Sunway exascale prototype system are highlighted,including the parallel operating system,input/output(I/O)optimization technology,ultra-large-scale parallel debugging technology,10-million-core parallel algorithm,and mixed-precision method.Parallel operating systems and I/O optimization technology mainly support largescale system scaling,while the ultra-large-scale parallel debugging technology,10-million-core parallel algorithm,and mixed-precision method mainly enhance the efficiency of large-scale applications.Finally,the contributions to various applications running on the Sunway exascale prototype system are introduced,verifying the effectiveness of the parallel supporting environment design.
基金This work was supported by the grants from the National Natural Science Foundation of China(Nos.81100061 and 81670089)the Shanghai Municipal Commission of Health and Family Planning(No.201640225)+1 种基金the Science and Technology Commission of Shanghai Municipality(No.19411964100)the Startup Fund for scientific research,Fujian Medical University(No.2019 QH1278).
文摘oluntary contribution has become the only source of donor lungs in China since 2015.To elaborate the outcomes of patients awaiting lung transplantation(LTx)after the implementation of donation after brain death,we performed a retrospective study that encompassed 205 patients with end-stage lung disease who registered for LTx at Shanghai Pulmonary Hospital from January 1,2015 to January 1,2021.A total of 180 patients were enrolled in the study.The median waiting time was 1.25 months.Interstitial lung disease(ILD)(103/180,57.2%)and chronic obstructive pulmonary disease(COPD)(56/180,31.1%)were the most common diseases in our study population.The mean pulmonary artery pressure(mPAP)of patients in the died-waiting group was higher than that of the survivors(53.29+21.71 mmHg vs.42.11+18.58 mmHg,P-0.002).The mortality of patients with ILD(34/103,33.00%)was nearly twice that of patients with COPD(10/56,17.86%)while awaiting LTx(P-0.041).In the died-waiting group,patients with ILD had a shorter median waiting time than patients with COPD after being listed(0.865 months vs.4.720 months,P-0.030).ILD as primary disease and mPAP>35 mmHg were two significant independent risk factors for waitlist mortality,with hazard ratios(HR)of 3.483(95%CI 1.311-9.111;P-0.011)and 3.500(95%CI 1.435-8.536;P=0.006).Hence,LTx is more urgently needed in patients with ILD and pulmonary hypertension.
