A de novo missense mutation in MPP2 confers an increased risk of Vogt–Koyanagi–Harada disease as shown by trio-based whole-exome sequencing

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.

中国为什么可以实现陆相“页岩油革命”?

陆相页岩油是保障国家石油供应安全和提升工业创新水平的战略接替资源.中国是陆相石油资源大国,占陆上石油资源总量的90%;也是陆相石油生产大国,陆相石油产量约占石油总产量的93%(贾承造等,2018;杨智和邹才能,2019).中国源岩层系发育多种类型非常规油气资源(图1),其中陆相页岩油是中国陆上未来剩余石油资源的主要接替领域.确立中国特色陆相页岩油理论技术攻关的科学问题,有利于推动实现中国陆相页岩油革命和石油工业持续发展.目前,中高成熟度页岩油在松辽、鄂尔多斯、渤海湾、准噶尔、四川等盆地已实现工业性突破与发展,中低成熟度页岩油已经开展大量前期基础理论与技术储备攻关,即将在鄂尔多斯、松辽等盆地进行工业性试验。

Characteristics and resource prospects of tight oil in Ordos Basin, China

Efficient large-scale development of ultra-low-permeability reservoirs(0.3-1 mD)has been achieved in the Changqing Oilfield,Ordos Basin of China.According to unique features of petroleum exploration and development in this basin,tight oil herein refers to petroleum that occurs in oil-bearing shales and interbedded tight sandstone reservoirs adjacent to source rocks with ambient air permeability<0.3 mD.Tight oil in tight sandstone and shale have generally not yet experienced large-scale long-distance migration.In the Yanchang Formation,tight oil has mainly accumulated in the semi-deep to deep lacustrine facies,typically in oil-bearing shales and tight sandstones of the 7th member oil-bearing formation and tight sandstones of the 6th member oil-bearing formation in the center of the basin.Tight oil resource in the Ordos Basin is characterized by wide spatial distribution,excellent source rocks,extremely tight sandstone reservoirs,complex pore throat structures,poor physical properties,high oil saturation,good crude-oil properties,and low reservoir pressure.A fundamental feature of the continuous oil and gas accumulation in tight oil reservoirs is the widespread development of nano-scale pore-throat systems.In the Yanchang Formation,most of connected pore throats in tight sandstone reservoirs have diameters greater than critical pore throat diameter,allowing oil and gas migration in the tight reservoirs.According to contact relationship between tight reservoirs and source rocks,three types of tight oil reservoirs are identified in the Yanchang Formation,i.e.,tight massive sandstone reservoir,sand-shale interbed reservoir,and oil-bearing shale reservoir.In the Ordos Basin,tight oil is widely distributed in the 6th and 7th members of the Yanchang Formation,with total resources estimated to be 3×10^(9) t.These include>1×10^(9) t of oil resources in shale in the 7th member of the Yanchang Formation and approximately 0.9×10^(9) t and 1.1×10^(9) t of tight sandstone oil resource in the 6th and 7th members of the Yanchang Formation,respectively.These tight oil resources are the realistic resources addition for the oilfield,which can ensure an annual production of 50×10^(6) t of oil and gas equivalent and maintain long-term stable oil production in the Changqing Oilfield,Ordos Basin,China.

Why Can China Realize the Continental“Shale Oil Revolution”?

0 INTRODUCTION Continental shale oil is a strategic alternative resource to ensure the safety of national oil supply and improve the level of industrial innovation.China is a large country of continental oil resources,accounting for 90%of the total onshore oil resources;and China is also a major producer of continental oil,accounting for about 93%of the total oil production(Yang et al.,2019;Jia et al.,2018).