Photocatalytic Water Splitting of Al-Doped Rh<i>_x</i>Cr_2–<i>x</i>O₃/SrTiO₃ Synthesized by Flux Method: Elucidating the Role of Different Molten Salts

Photocatalytic water splitting is a promising approach to converting solar energy into green hydrogen. As an effective photocatalyst, RhxCr2–xO3/SrTiO3 has been widely studied for water splitting, mainly synthesized using SrCl2 molten salt as the reaction media. This research systematically studied the effect of molten salts and Al doping in order to test and integrate the combinatorial effect of the modifications of SrTiO3-based catalysts. A series of SrTiO3 and Al-doped SrTiO3 (Al:SrTiO3) were synthesized by the flux method with three molten salts (NaCl, KCl, and SrCl2·6H2O) at different annealing temperatures (900 and 1000 °C). Cocatalyst, RhxCr2–xO3, was loaded on the surface of Al-doped SrTiO3 by impregnation and photodeposition methods for comparison. The photocatalytic performance of overall water splitting was evaluated in pure water under UV and AM 1.5G simulated sunlight. A significant improvement in photocatalytic activity was observed in Al-doped RhxCr2–xO3/SrTiO3. Especially Al-doped RhxCr2–xO3/SrTiO3 synthesized by KCl molten salt showed the highest hydrogen evolution rate with the synergy effect of molten salt and Al doping. Furthermore, hydrogen evolution rates were further enhanced by loading core–shell RhxCr2–xO3 using in situ photodeposition instead of impregnation, reaching 784 and 431 μmol h–1 g–1 H2 under 365 nm UV light and AM 1.5G irradiation, respectively

LocusZoom plot of <i>MMP12</i> association using age-at-onset informed approach.

<p>SNPs are colored based on their correlation (r²) with the labeled top SNP, which has the smallest P value in the region. The fine-scale recombination rates estimated from 1000 Genomes (EUR) data are marked in light blue, with genes marked below by horizontal blue lines. Arrows on the horizontal blue lines show the direction of transcription, and rectangles are exons. SNP p-values are from the discovery meta-analysis only with the exception of rs660599, for which the given p-value indicates the overall evidence for association from the discovery and replication cohorts.</p

Sample size of discovery populations.

<p>IS, all ischaemic stroke; CE, cardioembolic stroke; LAA, large artery stroke; SVD, small vessel disease.</p

Evaluation of evidence genome-wide for SNPs exhibiting greater significance using the age-at-onset informed approach compared to permutations.

<p>-log10(p value) from permutations for evidence of age-at-onset effect at given SNP p-value selection threshold shown in red; median proportion of SNPs (with IQR) more significant in observed age-at-onset informed meta-analysis compared to permutations shown in blue; horizontal line at p = 0.05 in red; horizontal line at median proportion of SNP = 0.5 in blue; IS, all ischaemic stroke; CE, cardioembolic stroke; LAA, large artery atherosclerotic stroke; SVD, small vessel disease. See <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004469#pgen.1004469.s009" target="_blank">Table S5</a> for number of SNPs included at each p-value selection threshold.</p

Evidence for association of A allele of rs660599 (chromosome 11; Base position 102,234,967) with large artery atherosclerotic stroke and all ischaemic stroke.

<p>LAA, large artery stroke; IS, all ischaemic stroke; SNP, single nucleotide polymorphism; RAF, risk allele frequency; OR, odds ratio; 95% CI, 95% confidence interval; EUR, meta-analysis in individuals of European ancestry alone; ALL, trans-ethnic meta-analysis of all individuals. Forest plots of effect sizes and standard errors for each replication centre are given in Figures S3, S4.</p

Sample size of replication populations.

<p>LAA, large artery stroke; IS, all ischaemic stroke; ARIC, the Atherosclerosis Risk in communities study; ASGC, the Australian Stroke Genetics collaboration; deCODE, deCODE genetics; GEOS, the Genetics of early onset stroke study; HVH, the heart and vascular health study; ISGS/SWISS, the Ischaemic stroke genetics study/Siblings with Ischaemic stroke study; MGH-GASROS, Massachusetts General Hospital – Genetics affecting stroke risk and outcome; PROMISe, Prognostic modeling in ischaemic stroke study <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004469#pgen.1004469-Achterberg1" target="_blank">[55]</a>; RACE, Risk Assessment of Cerebrovascular Events study. For further details of these populations please see the original METASTROKE publication <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004469#pgen.1004469-Traylor2" target="_blank">[16]</a>.</p

SNPs associated with primary insulin secretion traits at genome-wide significance levels.

<p>The results are from the meta-analyses of the discovery GWAS, CardioMetabochip and <i>de novo</i> genotyping. Results are reported for the directly genotyped and imputed SNPs tested for association with insulin secretion measured as CIR and AUC_Ins/AUC_Gluc (trait abbreviations are listed in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004235#s4" target="_blank">Methods</a> “Phenotype definition” section). Freq denotes the allele frequency of the insulin secretion-reducing allele. N = sample size. Since the index SNP rs933360 (A/G) from the discovery GWAS was not present on the CardioMetabochip platform, a variant (rs6943153 (C/T)) in strong LD with the former (r² = 0.82) was used as a proxy SNP for the meta-analyses.</p

<i>GRB10</i> expression in human islets.

<p>(A) Immunostainings demonstrating that <i>GRB10</i> (green, panel A, E) is abundantly expressed in β- (panel B, D), α- (panel C, D) and δ-cells (panel F, G) in human pancreatic islets. Arrows indicate co-localization with insulin (panel D) and somatostatin (panel G). Arrowheads indicate co-localization with glucagon (panel D). Scale bar = 50 µm. (B) Schematic representation of the <i>GRB10</i> gene and SNPs investigated in the present study. Grey boxes = untranslated exons. Black boxes = translated exons. (C) Examples of RT-PCR on islet cDNA (top six rows) and PCR on genomic DNA (gDNA, bottom row) from two individuals heterozygous for the reporter SNP rs1800504. The first column states the forward primer location of each PCR and a forward primer in exon 3 captures all transcripts. The peaks show the Sanger sequencing trace across rs1800504, which is underlined (A: green trace, G: black trace). Percentages indicate the contribution from the paternal allele (P.A.) (G-allele in the first case, A-allele in the second case). The paternal genotype is identified assuming complete maternal imprinting of the UN2 promoter, in line with previous findings <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004235#pgen.1004235-Monk1" target="_blank">[12]</a>. A sequence of heterozygous genomic DNA (gDNA) is shown on the bottom for comparison (50%-50%). (D) To study if DNA methylation of <i>GRB10</i> is tissue-specific, the degree of methylation was analyzed at 3 CpG sites located ∼31.7 kb downstream of rs933360 in both human pancreatic islets of 98 donors and PBL from 6 trios using EpiTYPER. The exact position of each analyzed CpG site in relation to rs933360 is given in the figure. Data are presented as mean ± SEM. * <i>p</i><0.05 for difference in methylation between human islets and PBL. (E) The <i>GRB10</i> mRNA levels correlated negatively with the degree of methylation at the CpG site located 31,675 bp downstream of <i>GRB10</i> rs933360.</p

Effects of disrupted <i>GRB10</i> through knock-down on islet function.

<p>(A) Disrupted <i>GRB10</i> in INS-1 rat β-cells markedly reduced glucose-stimulated insulin secretion. (B) <i>GRB10</i> knock-down showed reduced glucose-stimulated insulin secretion at 20 mM glucose and glucagon secretion at 1 mM glucose in human pancreatic islets (N_insulin = 7, N_glucagon = 6 donors of human pancreatic islets; 3–6 measurements in each experiment for each donor). (C) <i>GRB10</i> knock-down resulted in a reduction of insulin and glucagon mRNA expression (N = 3 donors of human pancreatic islets; 3 measurements in each experiment for each donor). * <i>p</i><0.05; ** <i>p</i><0.01, *** <i>p</i><0.001. Error bars denote SEM.</p

Parent-of-origin effect of <i>GRB10</i> rs933360 on insulin secretion and glucose levels.

<p>(A) No significant effect for CIR was observed from the paternally transmitted A-allele. (B) Carriers of the maternally transmitted A-allele showed lower CIR compared to the G-allele. (C) Carriers of the paternally transmitted A-allele had elevated fasting plasma glucose levels, whereas (D) the maternally transmitted A-allele was associated with lower fasting plasma glucose levels. Fin-Swe = Trios from Finland and Sweden, Amish = Amish Family Diabetes Study, Kuopio = Kuopio Offspring Study.</p