| 1 | A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing显示文摘Vogt–Koyanagi–Harada(VKH)disease is a leading cause of blindness in young and middle-aged people.However,the etiology of VKH disease remains unclear.Here,we performed the first trio-based whole-exome sequencing study,which enrolled 25 VKH patients and 50 controls,followed by a study of 2081 VKH patients from a Han Chinese population to uncover detrimental mutations.A total of 15 de novo mutations in VKH patients were identified,with one of the most important being the membrane palmitoylated protein 2(MPP2)p.K315N(MPP2-N315)mutation.The MPP2-N315 mutation was highly deleterious according to bioinformatic predictions.Additionally,this mutation appears rare,being absent from the 1000 Genome Project and Genome Aggregation Database,and it is highly conserved in 10 species,including humans and mice.Subsequent studies showed that pathological phenotypes and retinal vascular leakage were aggravated in MPP2-N315 mutation knock-in or MPP2-N315 adeno-associated virus-treated mice with experimental autoimmune uveitis(EAU).In vitro,we used clustered regularly interspaced short palindromic repeats(CRISPR‒Cas9)gene editing technology to delete intrinsic MPP2 before overexpressing wild-type MPP2 or MPP2-N315.Levels of cytokines,such as IL-1β,IL-17E,and vascular endothelial growth factor A,were increased,and barrier function was destroyed in the MPP2-N315 mutant ARPE19 cells.Mechanistically,the MPP2-N315 mutation had a stronger ability to directly bind to ANXA2 than MPP2-K315,as shown by LC‒MS/MS and Co-IP,and resulted in activation of the ERK3/IL-17E pathway.Overall,our results demonstrated that the MPP2-K315N mutation may increase susceptibility to VKH disease. | Xianyang Liu Jiayu Meng Xingyun Liao Yusen Liu Qian Zhou Zongren Xu Shuming Yin Qingfeng Cao Guannan Su Siyuan He Wanqian Li Xiaotang Wang Guoqing Wang Dali Li Peizeng Yang Shengping Hou | 2023 | Cellular & Molecular Immunology2023，20，11： | 0 |
| 3 | Water–solid contact electrification and catalysis adjusted by surface functional groups显示文摘Chemical functional groups on solid surfaces greatly influence contact electrification(CE)at water–solid interfaces.Previous studies of their effects mainly swapped materials or bonded related molecules to a substrate,introducing other factors of influence.This work aims at unambiguously demonstrating the role of functional groups in water-polymer CE.We study the contribution of functional groups,by using ion coupled plasma etching to modify a high-density polyethylene(HDPE)film,a polymer with a naturally quasi-null charge transfer ability.Fluoride(HDPE–F)and hydroxyl(HDPE–OH)functional groups are generated and endowed HDPE with charge withdrawing ability.HDPE–F withdraws 2.5–2.7 times more charges than HDPE–OH.Concurrently,the surface charges accumulated generate electrostatic forces,altering the droplets motion.This phenomenon provides another approach to study CE,helping to evaluate the contribution of electrons to solid–liquid CE.Finally,employing HDPE–F to perform contact-electro-catalysis shows its activity is 2.4 times higher than that of commercial fluorinated films. | Yusen Su Andy Berbille Zhong Lin Wang Wei Tang | 2024 | Nano Research2024，17，4： | 0 |
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