Molybdenum Phosphide Flakes Catalyze Hydrogen Generation in Acidic and Basic Solutions

Molybdenum phosphide (MoP) flakes were synthesized by the reduction of hexaammonium heptamolybdate tetrahydrate and ammonium dihydrogen phosphate. The flakes are porous and constructed by MoP nanoparticles with ca. 100 nm diameters. The lateral size of flakes ranges from less than 1 μm to larger than 5 μm, and the thickness of MoP fakes is ca. 200 nm. The mixture of MoP flakes and carbon black exhibits effective catalytic activity in the hydrogen evolution reaction. The optimal overpotential required for 20 mA·cm﹣2 current density is 155 mV in acidic solution and 184 mV in basic solution. The mixture can work stably in long-term hydrogen generation in both acidic and basic solution. The faradaic yield of mixture in hydrogen evolution reaction is nearly 100% in both acidic and basic solution. The Mo and P species in MoP flakes are found to have small positive and negative charge, respectively. The catalytic activity of MoP flakes is likely to be correlated with this charged nature.

Endorepellin和neurexin互作促进神经上皮细胞自噬并维持正常神经管发育

Heparan sulfate proteoglycan 2(HSPG2)gene encodes the matrix protein Perlecan,and genetic inactivation of this gene creates mice that are embryonic lethal with severe neural tube defects(NTDs).We discovered rare genetic variants of HSPG2 in 10%cases compared to only 4%in controls among a cohort of 369 NTDs.Endorepellin,a peptide cleaved from the domain V of Perlecan,is known to promote angiogenesis and autophagy in endothelial cells.The roles of enderepellin in neurodevelopment remain unclear so far.Our study revealed that endorepellin can migrate to the neuroepithelial cells and then be recognized and bind with the neuroepithelia receptor neurexin in vivo.Through the endocytic pathway,the interaction of endorepellin and neurexin physiologically triggers autophagy and appropriately modulates the differentiation of neural stem cells into neurons as a blocker,which is necessary for normal neural tube closure.We created knock-in(KI)mouse models with human-derived HSPG2 variants,using sperm-like stem cells that had been genetically edited by CRISPR/Cas9.We realized that any HSPG2 variants that affected the function of endorepellin were considered pathogenic causal variants for human NTDs given that the severe NTD phenotypes exhibited by these KI embryos occurred in a significantly higher response frequency compared to wildtype embryos.Our study provides a paradigm for effectively confirming pathogenic mutations in other genetic diseases.Furthermore,we demonstrated that using autophagy inhibitors at a cellular level can repress neuronal differentiation.Therefore,autophagy agonists may prevent NTDs resulting from failed autophagy maintenance and neuronal over-differentiation caused by deleterious endorepellin variants.

基因组结构变异研究的前瞻性及临床应用

The challenges and breakthroughs in human genetics can largely depend on the depth of exploring the missing heritability[1]and understanding of genetic variants,which enabled scientists to better elucidate the underlying causes of diseases and apply this knowledge in clinical settings.Human genomes differ from one individual to another in the form of single nucleotide variants(SNVs),small insertions and deletions(indels)(<50 base pairs(bp)),and structural variants(SVs)[2].

右位心的患病阈值和多因素遗传模式

右位心指正常生长于左侧的心脏位置或方向发生异常,常伴发复杂的先天性心脏病(先心),发病率约为十万分之八大规模小鼠表型的正向遗传学筛查表明,纤毛基因在先心的发病机制中起着关键作用。然而,右位心这类复杂先天性畸形的遗传模式,其中的遗传病因是否受纤毛基因驱动,以及适用于复杂性状的“全基因”模型能否解释尚不清楚。基于194名右位心患者及对照样本全基因组外显子测序的遗传学分析发现,“单例功能丧失性变异”(Singletonlossof functionvariant,SLoFV)的总数目与右位心显著相关(P=6.4x10-49).当个体携带的SLoFV个数大于8时,携带者发生右位心的风险呈指数增加。进一步通过斑马鱼模型,发现敲降心脏特异性高表达的核心基因,导致心脏结构的致畸率显著高于其他类型的相关基因.结果表明右位心存在基于SLoFV的全基因组遗传风险阈值,并证实了不同权重基因对心脏致畸的不同效应,丰富了全基因组模型下对核心基因遗传效应的理解,为理解复杂疾病右位心的遗传发病机制提供新的理论基础。