Nucleic acid detection plays a key role in diverse diagnosis and disease control.Currently available nucleic acid detection techniques are challenged by trade-offs among speed,simplicity,precision and cost.Here,we des...Nucleic acid detection plays a key role in diverse diagnosis and disease control.Currently available nucleic acid detection techniques are challenged by trade-offs among speed,simplicity,precision and cost.Here,we described a novel method,designated SENSOR(Sulfur DNA mediated nucleic acid sensing platform),for rapid nucleic acid detection.SENSOR was developed from phosphorothioate(PT)-DNA and sulfur binding domain(SBD)which specifically binds double-stranded PT-modified DNA.SENSOR utilizes PT-DNA oligo and SBD as targeting module,which is linked with split luciferase reporter to generate luminescence signal within 10 min.We tested detection on synthesized nucleic acid and COVID-19 pseudovirus,achieving attomolar sensitivity combined with an amplification procedure.Single nucleotide polymorphisms(SNP)could also be discriminated.Indicating SENSOR a new promising nucleic acid detection technique.展开更多
Nimodipine might be effective in subcortical vascular dementia(VaD). Its benefit in preventing further cognitive decline in patients with acute ischemic stroke(AIS) and vascular mild cognitive impairment(VaMCI) remain...Nimodipine might be effective in subcortical vascular dementia(VaD). Its benefit in preventing further cognitive decline in patients with acute ischemic stroke(AIS) and vascular mild cognitive impairment(VaMCI) remains to be established. In this multicenter, double-blind trial, we randomly assigned 654 eligible patients to nimodipine 30 mg three times a day or placebo. The primary outcome was any cognitive decline defined by the changes on the Mini-Mental State Examination(DMMSE à3) or vascular AD assessment scale cognitive subscale(DADAS-cog ! 4) at 6 months. Secondary outcomes included any distribution shift of DADAS-cog, DMMSE or cognitive improvement defined by DADAS-cog à2, or DMMSE ! 0. The primary outcome in the nimodipine group and placebo group were similar for DMMSE à3(4.18% and 7.22%, respectively, P = 0.15) and DADAS-cog ! 4(8.36% and 8.93% respectively,P = 0.88). The distribution shift of DADAS-cog and DMMSE differed significantly between the two groups(P = 0.03 and P = 0.05 respectively). Cognitive improvement occurred in 55.4% in the nimodipine group and 43.6% in the placebo group measured by DADAS-cog à2(Odds Ratio, 1.54; 95% confidence interval[CI] 1.10–2.14, P < 0.01) or 84.0% and 74.6% respectively by DMMSE ! 0(Odds Ratio, 1.79; 95% CI 1.18–2.70, P < 0.01). Nimodipine was associated with better cognitive function in the memory domain. The adverse events rate was similar in two groups. This study is registered with ClinicalTrials.gov,NCT01220622. Nimodipine did not show benefit to prevent cognitive decline in AIS patients with VaMCI, but improved cognition moderately, especially measured in the memory domain.展开更多
Interferon-γ(IFN-γ),secreted by activated T cells predominantly,plays a crucial performance in the tumoricidal immune response.Unfortunately,a high level of IFN-γseverely ignites the immunosuppressive response,espe...Interferon-γ(IFN-γ),secreted by activated T cells predominantly,plays a crucial performance in the tumoricidal immune response.Unfortunately,a high level of IFN-γseverely ignites the immunosuppressive response,especially by increasing the expression of immune checkpoint programmed death-ligand 1(PD-L1)and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1(IDO-1).Herein,we have explored a versatile IFN-γ-nano-integrator(aPD-L1-SH@Ce6@NLG919-PEG,simplified as CNDP)to establish a positive anti-tumor feedback loop to amplify the IFN-γ-mediated tumoricidal effect.In this nanointegrator,photosensitizer chlorin e6(Ce6)mediates photodynamic therapy(PDT)to re-shape immunogenicity and activate the adaptive immune response,followed by the secretion of high-level IFN-γto struggle tumor cells.IDO-1 inhibitor(NLG919)afterwards mitigates the immunosuppressive behavior of IFN-γby neutralizing the function of IDO-1.To turn“waste”into wealth,anti-PD-L1(aPD-L1)antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 blockade.Together,this“three musketeers”nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy.展开更多
基金supported by the National Natural Science Foundation of China(31900060)National Key Research and Development Program of China(2020YFA0907800,2022YFC3400200,2022YFA0912200)+1 种基金Natural Science Foundation of Shanghai(20ZR1414500)Shanghai Pilot Program for Basic Research-Shanghai Jiao Tong University(21TQ1400204).
文摘Nucleic acid detection plays a key role in diverse diagnosis and disease control.Currently available nucleic acid detection techniques are challenged by trade-offs among speed,simplicity,precision and cost.Here,we described a novel method,designated SENSOR(Sulfur DNA mediated nucleic acid sensing platform),for rapid nucleic acid detection.SENSOR was developed from phosphorothioate(PT)-DNA and sulfur binding domain(SBD)which specifically binds double-stranded PT-modified DNA.SENSOR utilizes PT-DNA oligo and SBD as targeting module,which is linked with split luciferase reporter to generate luminescence signal within 10 min.We tested detection on synthesized nucleic acid and COVID-19 pseudovirus,achieving attomolar sensitivity combined with an amplification procedure.Single nucleotide polymorphisms(SNP)could also be discriminated.Indicating SENSOR a new promising nucleic acid detection technique.
基金supported by the National 11th&12th Five Year S&T Major Projects(2011BAI08B01,2011BAI08B02)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China(2013BAI09B03)+1 种基金the Ministry of Science and Technology of China(2012ZX09303-005-001)Beijing Biobank of Cerebral Vascular Disease(D131100005313003)
文摘Nimodipine might be effective in subcortical vascular dementia(VaD). Its benefit in preventing further cognitive decline in patients with acute ischemic stroke(AIS) and vascular mild cognitive impairment(VaMCI) remains to be established. In this multicenter, double-blind trial, we randomly assigned 654 eligible patients to nimodipine 30 mg three times a day or placebo. The primary outcome was any cognitive decline defined by the changes on the Mini-Mental State Examination(DMMSE à3) or vascular AD assessment scale cognitive subscale(DADAS-cog ! 4) at 6 months. Secondary outcomes included any distribution shift of DADAS-cog, DMMSE or cognitive improvement defined by DADAS-cog à2, or DMMSE ! 0. The primary outcome in the nimodipine group and placebo group were similar for DMMSE à3(4.18% and 7.22%, respectively, P = 0.15) and DADAS-cog ! 4(8.36% and 8.93% respectively,P = 0.88). The distribution shift of DADAS-cog and DMMSE differed significantly between the two groups(P = 0.03 and P = 0.05 respectively). Cognitive improvement occurred in 55.4% in the nimodipine group and 43.6% in the placebo group measured by DADAS-cog à2(Odds Ratio, 1.54; 95% confidence interval[CI] 1.10–2.14, P < 0.01) or 84.0% and 74.6% respectively by DMMSE ! 0(Odds Ratio, 1.79; 95% CI 1.18–2.70, P < 0.01). Nimodipine was associated with better cognitive function in the memory domain. The adverse events rate was similar in two groups. This study is registered with ClinicalTrials.gov,NCT01220622. Nimodipine did not show benefit to prevent cognitive decline in AIS patients with VaMCI, but improved cognition moderately, especially measured in the memory domain.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(Nos.32171318 and 32101069)the Faculty of Health Sciences,University of Macao,the Start-up Research Grant(SRG)of University of Macao(No.SRG2018-00130-FHS)+2 种基金the Science and Technology Development Fund,Macao SAR(Nos.0109/2018/A3,0011/2019/AKP,0113/2019/A2,and 0103/2021/A)Shenzhen Science and Technology Innovation Commission,Shenzhen-Hong Kong-Macao Science and Technology Plan C(No.SGDX20201103093600004)We appreciate the assistance and support from the Proteomics,Metabolomics and Drug Development Core,Animal Research Core,and Biological Imaging and Stem Cell Core in the Faculty of Health Sciences,University of Macao.
文摘Interferon-γ(IFN-γ),secreted by activated T cells predominantly,plays a crucial performance in the tumoricidal immune response.Unfortunately,a high level of IFN-γseverely ignites the immunosuppressive response,especially by increasing the expression of immune checkpoint programmed death-ligand 1(PD-L1)and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1(IDO-1).Herein,we have explored a versatile IFN-γ-nano-integrator(aPD-L1-SH@Ce6@NLG919-PEG,simplified as CNDP)to establish a positive anti-tumor feedback loop to amplify the IFN-γ-mediated tumoricidal effect.In this nanointegrator,photosensitizer chlorin e6(Ce6)mediates photodynamic therapy(PDT)to re-shape immunogenicity and activate the adaptive immune response,followed by the secretion of high-level IFN-γto struggle tumor cells.IDO-1 inhibitor(NLG919)afterwards mitigates the immunosuppressive behavior of IFN-γby neutralizing the function of IDO-1.To turn“waste”into wealth,anti-PD-L1(aPD-L1)antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 blockade.Together,this“three musketeers”nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy.
