RESUMEN

The pathogenetic events of liver disease are seemingly determined by factors linked to ethanol metabolism. The variations in genes encoding enzymes of the ethanol metabolic pathway can influence exposure to alcohol and thus may act as risk factors for the development of liver disease. The present study aimed to understand the genetic aspect of germline variations in ethanol metabolic pathway genes in two major categories of liver disease i.e. ALD and NAFLD. Targeted Re-sequencing was performed in the two disease categories along with healthy control followed by an assessment and evaluation of the variants in a case vs control manner. The pathogenicity prediction was evaluated using SIFT, PolyPhen, PROVEN, LRT, CADD, FATHMM, EIGEN, REVEL and VarSome, while MD simulation of a novel significant variant was performed using the GROMACS 5.1.4 package. The annotation of targeted re-sequencing results revealed 2172 variants in different locations of the genes. Upon recurrent assessment predominantly focusing on exonic missense variants from these genes of the alcohol metabolism pathway, the ALDH1L2 [c.337C > G, p.Pro113Ala, (rs199841702)] variant was found highly significant with comprehensive results. The amino acid substitution tool that predicted protein stability due to a point mutation showed a decrease in stability. The genotyping distribution of the identified novel variant in the population revealed that heterozygosity is significantly distributed in ALD patients. However, the predominant association between the inherited variant and the cause of developing disease needs further robust study.

Asunto(s)

Predisposición Genética a la Enfermedad , Enfermedad del Hígado Graso no Alcohólico , Humanos , Mutación de Línea Germinal , Etanol , Células Germinativas

RESUMEN

Tuning composition of Pd-based bimetallic electrocatalysts of high stability and durability is of great importance in energy-related reactions. This study reports the remarkable electrocatalytic performance of carbon-supported bimetallic Pd-Cu alloy nanoparticles (NPs) towards formic acid oxidation (FAO) and oxygen reduction reaction (ORR). Among various bimetallic compositions, Pd3Cu/C alloy NPs exhibits the best FAO and ORR activity. During FAO reaction, Pd3Cu/C alloy NPs exhibits a peak with a current density of 28.33 mA cm-2 and a potential of 0.2 V (vs. Ag/AgCl) which is higher than that of the other PdCu compositions and standard 20 wt% Pd/C catalyst. Meanwhile, the onset potential (-0.09 V), half-wave potential (-0.18 V), limiting current density at 1600 rpm (-4.9 mA cm-2) and Tafel slope (64 mV dec-1) values of Pd3Cu/C alloy NPs validate its superiority over the conventional 20 wt% Pt/C catalyst for ORR. Experimental and DFT studies have confirmed that the enhanced activity can be attributed to the electronic effect that arises after Cu alloying which causes a downshift of Pd d-band center and structural effect that produces highly dispersed NPs over the carbon matrix with high electrochemically active surface area.