Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 i...Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.展开更多
The rational design and precise synthesis of multifunctional hybrid nanostructures with a tailored active core and a large, dendritic, modified mesoporous structured shell can promote catalysis, energy storage, and bi...The rational design and precise synthesis of multifunctional hybrid nanostructures with a tailored active core and a large, dendritic, modified mesoporous structured shell can promote catalysis, energy storage, and biological applications. Here, an oil-water biphase stratification coating strategy has been developed to prepare monodisperse magnetic dendritic mesoporous silica core-shell structured nano- spheres. These sophisticated Fe3O4@SiO2@dendritic-mSiO2 nanospheres feature large dendritic open pores （2.7 and 10.3 nm）. Significantly, the silica shells can be converted into dendritic mesoporous aluminosilicate frameworks with unchanged porosity, a Si/Al molar ratio of 14, and remarkably strong acidic sites, through a post-synthesis approach. In addition, the resultant magnetic dendritic mesoporous aluminosilicate nanospheres exhibit outstanding properties and promising application in phosphate removal from wastewater.展开更多
Amidst the rapid development of the Internet of Things (loT), Vehicular Ad-Hoc NETwork (VANET), a typical loT application, are bringing an ever-larger number of intelligent and convenient services to the daily lives o...Amidst the rapid development of the Internet of Things (loT), Vehicular Ad-Hoc NETwork (VANET), a typical loT application, are bringing an ever-larger number of intelligent and convenient services to the daily lives of individuals. However, there remain challenges for VANETs in preserving privacy and security. In this paper, we propose the first lattice-based Double-Authentication-Preventing Ring Signature (DAPRS) and adopt it to propose a novel privacy-preserving authentication scheme for VANETs, offering the potential for security against quantum computers. The new construction is proven secure against chosen message attacks. Our scheme is more efficient than other ring signature in terms of the time cost of the message signing phase and verification phase, and also in terms of signature length. Analyses of security and efficiency demonstrate that our proposed scheme is provably secure and efficient in the application.展开更多
The solvent‐free oxidation of benzyl alcohol was studied using supported Pd‐Ni bimetallic nanoparticles.Compared with monometallic Pd,the addition of Ni to Pd was found to be effective in suppressing the nondesired ...The solvent‐free oxidation of benzyl alcohol was studied using supported Pd‐Ni bimetallic nanoparticles.Compared with monometallic Pd,the addition of Ni to Pd was found to be effective in suppressing the nondesired product toluene,thereby enhancing the selectivity towards benzaldehyde.This result was attributed to a dual effect of Ni addition:the weakening of dissociative adsorption of benzyl alcohol and the promotion of oxygen species involved in the oxidation pathway.展开更多
A strategy of intensifying the visible light harvesting ability of anatase Ti02 hollow spheres(HSs)was developed,in which both sides of Ti02 HSs were utilised for stabilising Au nanoparticles(NPs)through the sacrifici...A strategy of intensifying the visible light harvesting ability of anatase Ti02 hollow spheres(HSs)was developed,in which both sides of Ti02 HSs were utilised for stabilising Au nanoparticles(NPs)through the sacrificial templating method and convex surface-induced confinement.The composite structure of single Au NP yolk-Ti02 shell-Au NPs,denoted as Au@Au(Ti02,was rendered and confirmed by the transmission electron microscopy analysis.Au@Au(Ti02 showed enhanced photocatalytic activity in the degradation of methylene blue and phenol in aqueous phase under visible light surpassing that of other reference materials such as Au(Ti02 by 77%and Au@P25 by 52%,respectively,in phenol degradation.展开更多
Vertebral lamina milling task is one of the high-risk operations in spinal surgeries. The operation is to remove part of vertebral lamina and release the pressure on the spinal nerve. Because many important vessels an...Vertebral lamina milling task is one of the high-risk operations in spinal surgeries. The operation is to remove part of vertebral lamina and release the pressure on the spinal nerve. Because many important vessels and nerves are under the vertebral lamina, any incorrect operation may cause irreparable damage to patients. To improve the safety of lamina milling task, a fuzzy force control strategy is proposed in this paper. Primary experiments have been conducted on bone samples from different animals. The results show that, with the fuzzy force control strategy, the bone milling system can recognize all surgery states and halt the tool at the proper location, achieving satisfactory surgery performance.展开更多
Respiratory syncytial virus(RSV)is the major cause of bronchiolitis and pneumonia in young children and the elderly.There are currently no approved RSV-specific therapeutic small molecules available.Using high-through...Respiratory syncytial virus(RSV)is the major cause of bronchiolitis and pneumonia in young children and the elderly.There are currently no approved RSV-specific therapeutic small molecules available.Using high-throughput antiviral screening,we identified an oral drug,the prenylation inhibitor lonafarnib,which showed potent inhibition of the RSV fusion process.Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells(HBEC).Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry,but has farnesyltransferase-independent antiviral efficacy.Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation.Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab.Furthermore,lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice.Collectively,lonafarnib could be a potential fusion inhibitor for RSV infection.展开更多
基金This study was funded by RemeGen Co.,Ltd.This work was also supported by the National Natural Science Foundation of China(No.91959205)the Ministry of Science and Technology of China(No.2017YFC1308900,No.2018ZX09201-015)Beijing Municipal Health Commission(No.2020-1-1022)。
文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.
基金We acknowledge the financial support from State Key Laboratory of Pollution Control and Resource Reuse Foundation （No. PCRRF14017）, the National Natural Science Foundation of China （No. 21210004） and the China Postdoctoral Science Foundation （No. 2014M551455）. J. P. Y. appreciates the funding supported by the Commonwealth of Australia through the Automotive Australia 2020 Cooperative Research Centre （Auto CRC） and DP120101194. The authors would like to thank Dr. T. Silver for critical reading of this manuscript.
文摘The rational design and precise synthesis of multifunctional hybrid nanostructures with a tailored active core and a large, dendritic, modified mesoporous structured shell can promote catalysis, energy storage, and biological applications. Here, an oil-water biphase stratification coating strategy has been developed to prepare monodisperse magnetic dendritic mesoporous silica core-shell structured nano- spheres. These sophisticated Fe3O4@SiO2@dendritic-mSiO2 nanospheres feature large dendritic open pores （2.7 and 10.3 nm）. Significantly, the silica shells can be converted into dendritic mesoporous aluminosilicate frameworks with unchanged porosity, a Si/Al molar ratio of 14, and remarkably strong acidic sites, through a post-synthesis approach. In addition, the resultant magnetic dendritic mesoporous aluminosilicate nanospheres exhibit outstanding properties and promising application in phosphate removal from wastewater.
基金supported by the National Key R&D(973)Program of China(No.2017YFB0802000)the National Natural Science Foundation of China(Nos.61772326,61572303,61872229,and 61802239)+4 种基金the NSFC Research Fund for International Young Scientists(No.61750110528)the National Cryptography Development Fund during the 13th Five-Year Plan Period(Nos.MMJJ20170216 and MMJJ201701304)the Foundation of State Key Laboratory of Information Security(No.2017-MS-03)the Fundamental Research Funds for the Central Universities(No.GK201702004,GK201803061,and 2018CBLY006)the China Postdoctoral Science Foundation(No.2018M631121)
文摘Amidst the rapid development of the Internet of Things (loT), Vehicular Ad-Hoc NETwork (VANET), a typical loT application, are bringing an ever-larger number of intelligent and convenient services to the daily lives of individuals. However, there remain challenges for VANETs in preserving privacy and security. In this paper, we propose the first lattice-based Double-Authentication-Preventing Ring Signature (DAPRS) and adopt it to propose a novel privacy-preserving authentication scheme for VANETs, offering the potential for security against quantum computers. The new construction is proven secure against chosen message attacks. Our scheme is more efficient than other ring signature in terms of the time cost of the message signing phase and verification phase, and also in terms of signature length. Analyses of security and efficiency demonstrate that our proposed scheme is provably secure and efficient in the application.
基金supported by National Natural Science Foundation of China(21271153,21373181,21222307,U1402233)Major Research Plan of National Natural Science Foundation of China(91545113)the Fundamental Research Funds for the Central Universities(2014XZZX003-02)~~
文摘The solvent‐free oxidation of benzyl alcohol was studied using supported Pd‐Ni bimetallic nanoparticles.Compared with monometallic Pd,the addition of Ni to Pd was found to be effective in suppressing the nondesired product toluene,thereby enhancing the selectivity towards benzaldehyde.This result was attributed to a dual effect of Ni addition:the weakening of dissociative adsorption of benzyl alcohol and the promotion of oxygen species involved in the oxidation pathway.
文摘A strategy of intensifying the visible light harvesting ability of anatase Ti02 hollow spheres(HSs)was developed,in which both sides of Ti02 HSs were utilised for stabilising Au nanoparticles(NPs)through the sacrificial templating method and convex surface-induced confinement.The composite structure of single Au NP yolk-Ti02 shell-Au NPs,denoted as Au@Au(Ti02,was rendered and confirmed by the transmission electron microscopy analysis.Au@Au(Ti02 showed enhanced photocatalytic activity in the degradation of methylene blue and phenol in aqueous phase under visible light surpassing that of other reference materials such as Au(Ti02 by 77%and Au@P25 by 52%,respectively,in phenol degradation.
文摘Vertebral lamina milling task is one of the high-risk operations in spinal surgeries. The operation is to remove part of vertebral lamina and release the pressure on the spinal nerve. Because many important vessels and nerves are under the vertebral lamina, any incorrect operation may cause irreparable damage to patients. To improve the safety of lamina milling task, a fuzzy force control strategy is proposed in this paper. Primary experiments have been conducted on bone samples from different animals. The results show that, with the fuzzy force control strategy, the bone milling system can recognize all surgery states and halt the tool at the proper location, achieving satisfactory surgery performance.
基金supported by the Natural Science Foundation of Guangdong province(Grant no.2024A1515011589 to Q.Y.)the National Natural Science Foundation of China(Grant no.32000111 to Q.Y.,82170473 to J.S.)+3 种基金the Pearl River Talent Recruitment Program(Grant no.2019CX01Y422 to X.C.)the Guangzhou Laboratory(Grant no.SRPG22-002 to J.S.and X.C.,No.SRPG22-011 to W.P.and Q.Y.)the Basic and Applied Basic Research Projects of Guangzhou Basic Research Program(2023A04J0161 to Q.Y.,2021QN020451 to J.S.)the Young Elite Scientists Sponsorship Program by CAST(Grant no.2023QNRC001 to F.L.).
文摘Respiratory syncytial virus(RSV)is the major cause of bronchiolitis and pneumonia in young children and the elderly.There are currently no approved RSV-specific therapeutic small molecules available.Using high-throughput antiviral screening,we identified an oral drug,the prenylation inhibitor lonafarnib,which showed potent inhibition of the RSV fusion process.Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells(HBEC).Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry,but has farnesyltransferase-independent antiviral efficacy.Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation.Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab.Furthermore,lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice.Collectively,lonafarnib could be a potential fusion inhibitor for RSV infection.
