| 1 | Targeting of anti-microbial proteins to the hyphal surface amplifies protection of crop plants against Phytophthora pathogens显示文摘Phytophthora pathogens are a persistent threat to the world's commercially important agricultural crops,including potato and soybean.Current strategies aim at reducing crop losses rely mostly on disease-resistance breeding and chemical pesticides,which can be frequently overcome by the rapid adaptive evolution of pathogens.Transgenic crops with intrinsic disease resista nee offer a promising alternative and con tinue to be developed.Here,we explored Phytophthora-derived PI3P(phosphatidylinositol 3-phosphate)as a novel control target,using proteins that bind this lipid to direct secreted anti-microbial peptides and proteins(AMPs)to the surface of Phytophthora pathogens.In transgenic Nicotiana benthamiana,soybean,and potato plants,significantly enhanced resistance to different pathogen isolates was achieved by expression of two AMPs(GAFP1 or GAFP3 from the Chinese medicinal herb Gastrodia elata)fused with a PI3P-specific binding domain(FYVE).Using the soybean pathogen P.sojae as an example,we demonstrated that the FYVE domain could boost the activities of GAFPs in multiple independent assays,including those performed in vitro,in vivo,and in planta.Mutational analysis of P.sojae PI3K1 and PI3K2 genes of this pathogen confirmed that the enhanced activities of the targeted GAFPs were correlated with PI3P levels in the pathogen.Collectively,our study provides a new strategy that could be used to confer resistance not only to Phytophthora pathogens in many plants but also potentially to many other kinds of plant pathogens with unique targets. | Yang Zhou Kun Yang Qiang Yan Xiaodan Wang Ming Cheng Jierui Si Xue Xue Danyu Shen Maofeng Jing Brett M.Tyler Daolong Dou | 2021 | Molecular Plant2021，14，8： | 2 |
| 2 | Monkeypox virus quadrivalent mRNA vaccine induces immune response and protects against vaccinia virus显示文摘Monkeypox has been declared a public health emergency by the World Health Organization.There is an urgent need for efficient and safe vaccines against the monkeypox virus(MPXV)in response to the rapidly spreading monkeypox epidemic.In the age of COVID-19,mRNA vaccines have been highly successful and emerged as platforms enabling rapid development and large-scale preparation.Here,we develop two MPXV quadrivalent mRNA vaccines,named mRNA-A-LNP and mRNA-B-LNP,based on two intracellular mature virus specific proteins(A29L and M1R)and two extracellular enveloped virus specific proteins(A35R and B6R).By administering mRNA-A-LNP and mRNA-B-LNP intramuscularly twice,mice induce MPXV specific IgG antibodies and potent vaccinia virus(VACV)specific neutralizing antibodies.Further,it elicits efficient MPXV specific Th-1 biased cellular immunity,as well as durable effector memory T and germinal center B cell responses in mice.In addition,two doses of mRNA-A-LNP and mRNA-B-LNP are protective against the VACV challenge in mice.And,the passive transfer of sera from mRNA-A-LNP and mRNA-B-LNP-immunized mice protects nude mice against the VACV challenge.Overall,our results demonstrate that mRNA-A-LNP and mRNA-B-LNP appear to be safe and effective vaccine candidates against monkeypox epidemics,as well as against outbreaks caused by other orthopoxviruses,including the smallpox virus. | Ye Sang Zhen Zhang Fan Liu Haitao Lu Changxiao Yu Huisheng Sun Jinrong Long Yiming Cao Jierui Mai Yiqi Miao Xin Wang Jiaxin Fang Youchun Wang Weijin Huang Jing Yang Shengqi Wang | 2023 | Signal Transduction and Targeted Therapy2023，8，5： | 0 |
| 3 | Associations between metabolic dysfunction-associated fatty liver disease and extrahepatic cancers:a cohort in China显示文摘Background:To evaluate the associations between a new definition of metabolic dysfunction-associated fatty liver disease(MAFLD)and extrahepatic cancers and compare with nonalcoholic fatty liver disease(NAFLD).Methods:We enrolled 151,391 Chinese participants in the Kailuan cohort.Hepatic steatosis was detected by abdominal ultrasound.Fine and Gray competing risk regression models were used to estimate hazard ratios(HRs)and 95%confidence interval(CI)between MAFLD and extrahepatic cancers.Results:MAFLD was associated with increased risk of prostate(HR=1.49,95%CI:1.07-2.08)and obesity-related cancers,including thyroid(HR=1.47,95%CI:1.01-2.12),kidney(HR=1.54,95%CI:1.18-2.00),colorectal(HR=1.15,95%CI:0.98-1.34)and breast cancer(HR=1.31,95%CI:1.04-1.66).The results were consistent in NAFLD vs.non-NAFLD and MAFLD-NAFLD vs.neither FLD.Compared with the neither FLD group,the NAFLD-only group had a higher risk of extrahepatic cancers(HR=1.57,95%CI:1.18-2.09),esophageal(HR=5.11,95%CI:2.25-11.62),and bladder cancer(HR=3.36,95%CI:1.23-9.17).The additional risk of extrahepatic cancers(HR=1.42,95%CI:1.17-1.73),esophageal(HR=4.37,95%CI:2.55-7.49),and breast cancer(HR=1.99,95%CI:1.01-3.92)was observed in MAFLD with metabolic dysregulation,and kidney(HR=1.83,95%CI:1.38-2.43),prostate(HR=1.46,95%CI:1.00-2.14)and breast cancer(HR=1.33,95%CI:1.02-1.74)was observed in MAFLD with overweight and metabolic dysregulation,as well as colorectal(HR=1.45,95%CI:1.07-1.96)and prostate cancer(HR=2.44,95%CI:1.42-4.21)in MAFLD with three risk factors.Additionally,MAFLD with excessive alcohol consumption would increase extrahepatic cancers(HR=1.14,95%CI:1.01-1.29)and breast cancer(HR=7.27,95%CI:2.33-22.69)risk.Conclusions:MAFLD and NAFLD shared similar excessive risks of obesity-related cancers,suggesting a driving role of FLD in these cancers.Metabolic dysregulation beyond obesity may play additional kidney,colorectal,and prostate cancer risks in MAFLD patients.It may be helpful in the clinic to relieve symptoms by treating metabolic disorders and preventing adverse outcomes of extrahepatic cancers. | Xiaojie Yuan Xiaomo Wang Shouling Wu Shuohua Chen Yanhong Wang Jierui Wang Ying Lu Yuanyuan Sun Qingjiang Fu Li Wang | 2023 | Hepatobiliary Surgery and Nutrition2023，12，5： | 0 |
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