Parkinson’s disease is characterized by synucleinopathy-associated neurodegeneration.Previous studies have shown that glucagon-like peptide-1(GLP-1)has beneficial effects in a mouse model of Parkinson’s disease indu...Parkinson’s disease is characterized by synucleinopathy-associated neurodegeneration.Previous studies have shown that glucagon-like peptide-1(GLP-1)has beneficial effects in a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.However,the effect of GLP-1 on intrinsic synuclein malfunction remains unclear.In this study,we investigated the effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism in SncaA53T transgenic mice and explored the underlying mechanisms.Our data showed that Lactococcus lactis MG1363-pMG36e-GLP-1 inhibited dopaminergic neuronal death,reduced pathological aggregation ofα-synuclein,and decreased movement disorders in SncaA53T transgenic mice.Furthermore,Lactococcus lactis MG1363-pMG36e-GLP-1 downregulated lipopolysaccharide-related inflammation,reduced cerebral activation of microglia and astrocytes,and promoted cell survival via the GLP-1 receptor/PI3K/Akt pathway in the substantia nigra.Additionally,Lactococcus lactis MG1363-pMG36e-GLP-1 decreased serum levels of pro-inflammatory molecules including lipopolysaccharide,lipopolysaccharide binding protein,interleukin-1β,and interleukin-6.Gut histopathology and western blotting further revealed that Lactococcus lactis MG1363-pMG36e-GLP-1 increased the expression of gut integrity-related proteins and reduced lipopolysaccharide-related inflammation by reversing gut dysbiosis in SncaA53T transgenic mice.Our findings showed that the beneficial effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism traits in SncaA53T transgenic mice is mediated by microglial polarization and the reversal of dysbiosis.Collectively,our findings suggest that Lactococcus lactis MG1363-pMG36e-GLP-1 is a promising therapeutic agent for the treatment of Parkinson’s disease.展开更多
A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rot...A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rotavirus gastroenteritis(RVGE).A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV(n?3200)or placebo(n?3200)group.All the subjects received three oral doses of vaccine four weeks apart.The vaccine efficacy(VE)against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season.VE against severe RVGE,VE against RVGE hospitalization caused by serotypes contained in HRV,and VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated.All adverse events(AEs)were collected for 30 days after each dose.Serious AEs(SAEs)and intussusception cases were collected during the entire study.Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21%(95%CI:53.31-79.69).VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36%(95%CI:78.45-96.53)and 89.21%(95%CI:64.51-96.72)respectively.VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88%(95%CI:49.11-72.92),85.51%(95%CI:72.74-92.30)and 83.68%(95%CI:61.34-93.11).Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable.There was no significant difference in incidences of SAEs in HRV and placebo groups.This study shows that this hexavalent reassortant rotavirus vaccine is an effective,well-tolerated,and safe vaccine for Chinese infants.展开更多
Virus-induced gene silencing （VIGS） offers a powerful approach for functional analysis of individual genes by knocking down their expression. We have adopted this approach to dissect gene functions in cotton resista...Virus-induced gene silencing （VIGS） offers a powerful approach for functional analysis of individual genes by knocking down their expression. We have adopted this approach to dissect gene functions in cotton resistant to Verticfllium wilt, one of the most devastating diseases worldwide. We showed here that highly efficient VIGS was obtained in a cotton breeding line （CA4002） with partial resistance to Verticillium wilt, and GhMKK2 and Gh Ve I are required for its resistance to Verticillium wilt. Arabidopsis AtBAK1/SERK3, a central regulator in plant disease resistance, belongs to a subfamily of somatic embryogenesis receptor kinases （SERKs） with five members, AtSERK1 to AtSERK5. Two BAK1 orthologs and one SERK1 ortholog were identified in the cotton genome. Importantly, GhBAK1 is required for CA4002 resistance to Verticillium wilt. Surprisingly, silencing of GhBAK1 is sufficient to trigger cell death accompanied with production of reactive oxygen species in cotton. This result is distinct from Arabidopsis in which AtBAK1 and AtSERK4 play redundant functions in cell death control. Apparently, cotton has only evolved SERK1 and BAK1 whereas AtSERK4/5 are newly evolved genes in Arabidopsis. Our studies indicate the functional importance of BAK1 in Verticillium wilt resistance and suggest the dynamic evolution of SERK family members in different plant species.展开更多
The coronavirus disease 2019(COVID-19)pandemic remains a significant global health challenge.Older adults are the population at high risk of developing severe COVID-19 or death[1–3].To date,dozens of vaccines for pro...The coronavirus disease 2019(COVID-19)pandemic remains a significant global health challenge.Older adults are the population at high risk of developing severe COVID-19 or death[1–3].To date,dozens of vaccines for prototype severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)have received emergency use authorization or conditional marketing approval in many countries[4].ZF2001,a protein subunit vaccine comprising two copies of tandem receptor-binding domain(RBD)from prototype SARS-CoV-2(HB-02 strain)[5,6],has demonstrated safety and immunogenicity in populations aged 3–17 and 18–59 after three doses of vaccination[7,8].Moreover,it has shown good efficacy in the prevention of symptomatic COVID-19 caused by infections from the alpha,kappa,and delta variants after a six-month follow-up for adults beyond 18 years of age in a phase 3 trial[9].ZF2001 was safe and well-tolerated in a large cohort of adults(R18 years of age),and the incidence of adverse events was lower among the participants 60 years of age or older than among those aged 18–59[9].However,its durability and immunogenicity in individuals 60 years of age and older have not been reported and need further investigation.Here,we reported the phase 1 trial of ZF2001 in adults aged 60 or older in China to determine the safety,tolerability,and immunogenicity of ZF2001 in older populations after short(1 month)-and long(6 months)-term follow-up.Moreover,we conducted a post-hoc analysis of serum samples to assess their neutralization capacity against omicron variants.展开更多
基金supported by grants from the Jiangxi Provincial Natural Science Foundation,No.20242BAB26134(to XF)the National Natural Science Foundation of China,Nos.82060638(to TC),82060222(to XF),82460237(to XF)+1 种基金the Major Disciplines of Academic and Technical Leaders Project of Jiangxi Province,Nos.20194BCJ22032(to TC),20213BCJL22049(to XF)Science and Technology Plan of Jiangxi Health Planning Committee,No.202210390(to XF).
文摘Parkinson’s disease is characterized by synucleinopathy-associated neurodegeneration.Previous studies have shown that glucagon-like peptide-1(GLP-1)has beneficial effects in a mouse model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.However,the effect of GLP-1 on intrinsic synuclein malfunction remains unclear.In this study,we investigated the effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism in SncaA53T transgenic mice and explored the underlying mechanisms.Our data showed that Lactococcus lactis MG1363-pMG36e-GLP-1 inhibited dopaminergic neuronal death,reduced pathological aggregation ofα-synuclein,and decreased movement disorders in SncaA53T transgenic mice.Furthermore,Lactococcus lactis MG1363-pMG36e-GLP-1 downregulated lipopolysaccharide-related inflammation,reduced cerebral activation of microglia and astrocytes,and promoted cell survival via the GLP-1 receptor/PI3K/Akt pathway in the substantia nigra.Additionally,Lactococcus lactis MG1363-pMG36e-GLP-1 decreased serum levels of pro-inflammatory molecules including lipopolysaccharide,lipopolysaccharide binding protein,interleukin-1β,and interleukin-6.Gut histopathology and western blotting further revealed that Lactococcus lactis MG1363-pMG36e-GLP-1 increased the expression of gut integrity-related proteins and reduced lipopolysaccharide-related inflammation by reversing gut dysbiosis in SncaA53T transgenic mice.Our findings showed that the beneficial effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism traits in SncaA53T transgenic mice is mediated by microglial polarization and the reversal of dysbiosis.Collectively,our findings suggest that Lactococcus lactis MG1363-pMG36e-GLP-1 is a promising therapeutic agent for the treatment of Parkinson’s disease.
基金supported by National Health Commission of the People’s Republic of China (grant number:2019ZX09302059)sponsored and funded by Wuhan Institute of Biological Products Co.,Ltd.,Hubei,China
文摘A randomized,double-blind,placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine(HRV)against rotavirus gastroenteritis(RVGE).A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV(n?3200)or placebo(n?3200)group.All the subjects received three oral doses of vaccine four weeks apart.The vaccine efficacy(VE)against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season.VE against severe RVGE,VE against RVGE hospitalization caused by serotypes contained in HRV,and VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated.All adverse events(AEs)were collected for 30 days after each dose.Serious AEs(SAEs)and intussusception cases were collected during the entire study.Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21%(95%CI:53.31-79.69).VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36%(95%CI:78.45-96.53)and 89.21%(95%CI:64.51-96.72)respectively.VE against RVGE,severe RVGE,and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88%(95%CI:49.11-72.92),85.51%(95%CI:72.74-92.30)and 83.68%(95%CI:61.34-93.11).Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable.There was no significant difference in incidences of SAEs in HRV and placebo groups.This study shows that this hexavalent reassortant rotavirus vaccine is an effective,well-tolerated,and safe vaccine for Chinese infants.
基金supported by funds from the Texas AgriLife Research Cotton Improvement Program to J.D.,T.W.,P.H., and L.S.the USDA National Institute of Food and Agriculture(Agriculture and Food Research Initiative Competitive Grants Program grant no.2012-67013-19433) to P.H.+1 种基金L.S.A.K.was supported by the NSF REU programF.L.was supported by the China Scholarship Council
文摘Virus-induced gene silencing （VIGS） offers a powerful approach for functional analysis of individual genes by knocking down their expression. We have adopted this approach to dissect gene functions in cotton resistant to Verticfllium wilt, one of the most devastating diseases worldwide. We showed here that highly efficient VIGS was obtained in a cotton breeding line （CA4002） with partial resistance to Verticillium wilt, and GhMKK2 and Gh Ve I are required for its resistance to Verticillium wilt. Arabidopsis AtBAK1/SERK3, a central regulator in plant disease resistance, belongs to a subfamily of somatic embryogenesis receptor kinases （SERKs） with five members, AtSERK1 to AtSERK5. Two BAK1 orthologs and one SERK1 ortholog were identified in the cotton genome. Importantly, GhBAK1 is required for CA4002 resistance to Verticillium wilt. Surprisingly, silencing of GhBAK1 is sufficient to trigger cell death accompanied with production of reactive oxygen species in cotton. This result is distinct from Arabidopsis in which AtBAK1 and AtSERK4 play redundant functions in cell death control. Apparently, cotton has only evolved SERK1 and BAK1 whereas AtSERK4/5 are newly evolved genes in Arabidopsis. Our studies indicate the functional importance of BAK1 in Verticillium wilt resistance and suggest the dynamic evolution of SERK family members in different plant species.
基金This work is funded by Anhui Zhifei Longcom Biopharmaceutical,National Key R&D Program of China(2021YFA1300803)the National Natural Science Foundation of China(82122031)We thank the staff of the Biosafety Level 3 Laboratory(Institute of Microbiology,Chinese Academy of Sciences)for their help in live virus experiments,Yawen Liu for her help in pseudovirus experiments,and Grammarly for text improvement.
文摘The coronavirus disease 2019(COVID-19)pandemic remains a significant global health challenge.Older adults are the population at high risk of developing severe COVID-19 or death[1–3].To date,dozens of vaccines for prototype severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)have received emergency use authorization or conditional marketing approval in many countries[4].ZF2001,a protein subunit vaccine comprising two copies of tandem receptor-binding domain(RBD)from prototype SARS-CoV-2(HB-02 strain)[5,6],has demonstrated safety and immunogenicity in populations aged 3–17 and 18–59 after three doses of vaccination[7,8].Moreover,it has shown good efficacy in the prevention of symptomatic COVID-19 caused by infections from the alpha,kappa,and delta variants after a six-month follow-up for adults beyond 18 years of age in a phase 3 trial[9].ZF2001 was safe and well-tolerated in a large cohort of adults(R18 years of age),and the incidence of adverse events was lower among the participants 60 years of age or older than among those aged 18–59[9].However,its durability and immunogenicity in individuals 60 years of age and older have not been reported and need further investigation.Here,we reported the phase 1 trial of ZF2001 in adults aged 60 or older in China to determine the safety,tolerability,and immunogenicity of ZF2001 in older populations after short(1 month)-and long(6 months)-term follow-up.Moreover,we conducted a post-hoc analysis of serum samples to assess their neutralization capacity against omicron variants.
