The continuous emergence of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines.Her...The continuous emergence of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines.Here,we report an open-labeled Phase I clinical trial of a modified mRNA vaccine(SYS6006)as a fourth-dose booster in healthy adults.Eighteen eligible participants,who had completed three doses of inactivated COVID-19 vaccines,received a fourth boosting dose of SYS6006-20μg.Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity.The primary endpoint of this trial was titers of anti-receptor binding domain of spike glycoprotein(RBD)antibodies of the Omicron strain(BA.2 and BA.4/5)in serum;titers of neutralizing antibodies against pseudovirus of the Omicron strain(BA.2 and BA.4/5).The secondary endpoint was the incidence of adverse events within 30 days after the boosting.The exploratory endpoint was the cellular immune responses(interferon gamma,IFN-γ).This trial was registered with the Chinese Clinical Trial Registry website.No serious adverse events were reported within 30 days after vaccination.No Grade 3 fever or serious adverse event was reported in the SYS6006 group.Notably,SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies(>90 days)compared with the convalescent group(P<0.0001)against Omicron strain(BA.2 and BA.4/5).Besides,higher positive spots of T-cell-secreting IFN-γwere observed in the SYS6006 group than those in the convalescent group(P<0.05).These data demonstrated that SYS6006 was well tolerated and highly immunogenic,generating a stronger and more durable immune response against different variants of SARS-CoV-2.展开更多
The chemical mechanical polishing/planarization(CMP) performance of an inhibitor-free alkaline copper slurry is investigated.The results of the Cu dissolution rate(DR) and the polish rate(PR) show that the alkal...The chemical mechanical polishing/planarization(CMP) performance of an inhibitor-free alkaline copper slurry is investigated.The results of the Cu dissolution rate(DR) and the polish rate(PR) show that the alkaline slurry without inhibitors has a relatively high copper removal rate and considerable dissolution rate.Although the slurry with inhibitors has a somewhat low DR,the copper removal rate was significantly reduced due to the addition of inhibitors(Benzotriazole,BTA).The results obtained from pattern wafers show that the alkaline slurry without inhibitors has a better planarization efficacy;it can planarize the uneven patterned surface during the excess copper removal.These results indicate that the proposed inhibitor-free copper slurry has a considerable planarization capability for CMP of Cu pattern wafers,it can be applied in the first step of Cu CMP for copper bulk removal.展开更多
In this paper,a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise strategy.The conjugation of peptides at either 3’-terminus of ...In this paper,a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise strategy.The conjugation of peptides at either 3’-terminus of siCdc2 bring no change to the classical A-form of RNA duplex,but slightly compromise the thermodynamic stability.Peptide conjugation at the 3’-terminus of sense strand could improve the serum stability obviously,however,the opposite peptide conjugation at the 3’-terminus of antisense strand shows no such influence.According to the results of artificial silencing activity assay system,peptide conjugation at 3’-terminus of antisense strand slightly weakens the silencing activity of siCdc2.But sense strand peptide conjugation exhibits similar silencing activity as native siCdc2,meanwhile,it could mitigate the unwanted off-target effect of sense strand targeting to its own mRNA.展开更多
We have developed an alkaline barrier slurry (named FA/O slurry) for barrier removal and evaluated its chemical mechanical planarization (CMP) performance through comparison with a commercially developed barrier s...We have developed an alkaline barrier slurry (named FA/O slurry) for barrier removal and evaluated its chemical mechanical planarization (CMP) performance through comparison with a commercially developed barrier slurry. The FA/O slurry consists of colloidal silica, which is a complexing and an oxidizing agent, and does not have any inhibitors. It was found that the surface roughness of copper blanket wafers polished by the FA/O slurry was lower than the commercial barrier slurry, demonstrating that it leads to a better surface quality. In addition, the dishing and electrical tests also showed that the patterned wafers have a lower dishing value and sheet resistance as compared to the commercial barrier slurry. By comparison, the FA/O slurry demonstrates good planarization performance and can be used for barrier CMP.展开更多
基金We thank CSPC Zhongqi Pharmaceutical Technology(Shijiazhuang)Co.,Ltd for providing the SYS6006 vaccines for this trialthe Hebei Provincial Department of Science and Technology(22372411D).
文摘The continuous emergence of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines.Here,we report an open-labeled Phase I clinical trial of a modified mRNA vaccine(SYS6006)as a fourth-dose booster in healthy adults.Eighteen eligible participants,who had completed three doses of inactivated COVID-19 vaccines,received a fourth boosting dose of SYS6006-20μg.Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity.The primary endpoint of this trial was titers of anti-receptor binding domain of spike glycoprotein(RBD)antibodies of the Omicron strain(BA.2 and BA.4/5)in serum;titers of neutralizing antibodies against pseudovirus of the Omicron strain(BA.2 and BA.4/5).The secondary endpoint was the incidence of adverse events within 30 days after the boosting.The exploratory endpoint was the cellular immune responses(interferon gamma,IFN-γ).This trial was registered with the Chinese Clinical Trial Registry website.No serious adverse events were reported within 30 days after vaccination.No Grade 3 fever or serious adverse event was reported in the SYS6006 group.Notably,SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies(>90 days)compared with the convalescent group(P<0.0001)against Omicron strain(BA.2 and BA.4/5).Besides,higher positive spots of T-cell-secreting IFN-γwere observed in the SYS6006 group than those in the convalescent group(P<0.05).These data demonstrated that SYS6006 was well tolerated and highly immunogenic,generating a stronger and more durable immune response against different variants of SARS-CoV-2.
基金supported by the Major National Science and Technology Special Projects,China(No.2009ZX02308)the Tianjin Natural Science Foundation of China(No.lOJCZDJC 15500)+1 种基金the National Natural Science Foundation of China(No.10676008)the Fund Project of Hebei Provincial Department of Education,China(No.2011128)
文摘The chemical mechanical polishing/planarization(CMP) performance of an inhibitor-free alkaline copper slurry is investigated.The results of the Cu dissolution rate(DR) and the polish rate(PR) show that the alkaline slurry without inhibitors has a relatively high copper removal rate and considerable dissolution rate.Although the slurry with inhibitors has a somewhat low DR,the copper removal rate was significantly reduced due to the addition of inhibitors(Benzotriazole,BTA).The results obtained from pattern wafers show that the alkaline slurry without inhibitors has a better planarization efficacy;it can planarize the uneven patterned surface during the excess copper removal.These results indicate that the proposed inhibitor-free copper slurry has a considerable planarization capability for CMP of Cu pattern wafers,it can be applied in the first step of Cu CMP for copper bulk removal.
基金supported by the National Natural Science Foundation of China(20932001)the Ministry of Science and Technology of China(2012AA022501)the National Key Basic Research Program of China(2012CB720604)
文摘In this paper,a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise strategy.The conjugation of peptides at either 3’-terminus of siCdc2 bring no change to the classical A-form of RNA duplex,but slightly compromise the thermodynamic stability.Peptide conjugation at the 3’-terminus of sense strand could improve the serum stability obviously,however,the opposite peptide conjugation at the 3’-terminus of antisense strand shows no such influence.According to the results of artificial silencing activity assay system,peptide conjugation at 3’-terminus of antisense strand slightly weakens the silencing activity of siCdc2.But sense strand peptide conjugation exhibits similar silencing activity as native siCdc2,meanwhile,it could mitigate the unwanted off-target effect of sense strand targeting to its own mRNA.
基金Project supported by the Major National Science and Technology Special Projects(No.2009ZX02308)the National Natural Science Foundation of China(No.10676008)+1 种基金the Tianjin Natural Science Foundation of China(No.10JCZDJC15500)the Fund Project of Hebei Provincial Department of Education,China(No.2011128)
文摘We have developed an alkaline barrier slurry (named FA/O slurry) for barrier removal and evaluated its chemical mechanical planarization (CMP) performance through comparison with a commercially developed barrier slurry. The FA/O slurry consists of colloidal silica, which is a complexing and an oxidizing agent, and does not have any inhibitors. It was found that the surface roughness of copper blanket wafers polished by the FA/O slurry was lower than the commercial barrier slurry, demonstrating that it leads to a better surface quality. In addition, the dishing and electrical tests also showed that the patterned wafers have a lower dishing value and sheet resistance as compared to the commercial barrier slurry. By comparison, the FA/O slurry demonstrates good planarization performance and can be used for barrier CMP.