Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms

Deoxyribonucleic acid (DNA) replication can be divided into three major steps: initiation, elongation and termination. Each time a human cell divides, these steps must be reiteratively carried out. Disruption of DNA replication can lead to genomic instability, with the accumulation of point mutations or larger chromosomal anomalies such as rearrangements. While cancer is the most common class of disease associated with genomic instability, several congenital diseases with dysfunctional DNA replication give rise to similar DNA alterations. In this review, we discuss all congenital diseases that arise from pathogenic variants in essential replication genes across the spectrum of aberrant replisome assembly, origin activation and DNA synthesis. For each of these conditions, we describe their clinical phenotypes as well as molecular studies aimed at determining the functional mechanisms of disease, including the assessment of genomic stability. By comparing and contrasting these diseases, we hope to illuminate how the disruption of DNA replication at distinct steps affects human health in a surprisingly cell-type-specific manner.     

Potassium titanate whiskers on the walls of cordierite honeycomb ceramics for soot catalytic combustion

In this paper, potassium titanate whiskers was prepared via the Molten salt synthesis on the surface of cordierite ceramics for the regeneration of diesel particulate filters (DPFs). SEM, EDS, XRD, FT-IR, TG-DSC and TPO were carried out to characterize the morphology, microstructure, growth mechanism and catalytic performance of the samples. Potassium titanate whiskers with diameter (100–500 nm) and length (about 3 μm) is tightly combined with the cordierite ceramic substrate. The catalyst performance investigation demonstrates that potassium titanate whiskers decrease the soot combustion temperature apparently. The soot combustion process was studied by thermal analysis tests, and the activation energy of the combustion reaction can be calculated using Freeman-Carroll method. The carbon oxidation activation energy is 14.009 kcal/mol, and the activation energy for the catalytic reaction with potassium titanate whiskers is 6.287 kcal/mol, it can be illustrated that potassium titanate whiskers/cordierite catalyst possess excellence performance for carbon catalytic combustion. The coarseness of the interface increased because potassium titanate whiskers grew on the cordierite substrate, and the trapping ability could improve. This unique microstructure has potential application in the DPF field.     

Molecular fingerprint and machine learning to accelerate design of high-performance homochiral metal–organic frameworks

Computational screening was employed to calculate the enantioseparation capabilities of 45 functionalized homochiral metal–organic frameworks (FHMOFs), and machine learning (ML) and molecular fingerprint (MF) techniques were used to find new FHMOFs with high performance. With increasing temperature, the enantioselectivities for (R,S)-1,3-dimethyl-1,2-propadiene are improved. The “glove effect” in the chiral pockets was proposed to explain the correlations between the steric effect of functional groups and performance of FHMOFs. Moreover, the neighborhood component analysis and RDKit/MACCS MFs show the highest predictive effect on enantioselectivities among the four ML classification algorithms with nine MFs that were tested. Based on the importance of MF, 85 new FHMOFs were designed, and a newly designed FHMOF, NO₂-NHOH-FHMOF, with high similarity to the optimal MFs achieved improved chiral separation performance, with enantioselectivities of 85%. The design principles and new chiral pockets obtained by ML and MFs could facilitate the development of new materials for chiral separation.