Microsatellite instability (MSI) refers to the hypermutability of short repetitive sequences in the genome caused by impaired DNA mismatch repair. Although MSI has been studied for decades, large ...amounts of sequencing data now available allows us to examine the molecular fingerprints of MSI in greater detail. Here, we analyse ∼8,000 exomes and ∼1,000 whole genomes of cancer patients across 23 cancer types. Our analysis reveals that the frequency of MSI events is highly variable within and across tumour types. We also identify genes in DNA repair and oncogenic pathways recurrently subject to MSI and uncover non-coding loci that frequently display MSI. Finally, we propose a highly accurate exome-based predictive model for the MSI phenotype. These results advance our understanding of the genomic drivers and consequences of MSI, and our comprehensive catalogue of tumour-type-specific MSI loci will enable panel-based MSI testing to identify patients who are likely to benefit from immunotherapy.
We performed comprehensive association analyses of common high-confidence gnomAD-reported copy number deletions (CNDs) with 60 quantitative traits from UK10K consortium WGS data.
The study made use ...of data generated by the UK10K Consortium. UK10K consortium WGS data consist of TwinsUK (n = 1754, middle-aged females) and ALSPAC (n = 1867, birth to adolescence) cohorts. UK10K consortium called 18,739 CNDs (hg19) with GenomeSTRiP software. After filtering out variants with minor allele frequency < 0.05 or HWE P < 1.0 × 10
, 1222 (TwinsUK) and 1211 (ALSPAC) CNDs remained for association analyses with 60 normalized quantitative traits.
We identified 23 genome-wide significant associations at 13 loci, among which 2 associations reached experiment-wide significance. We found that two common deletions in chromosome 4, located between WDR1 and ZNF518B (23.3 kb, dbVar ID:nssv15888957, 4:10211262-10,234,569 and 9.8 kb, dbVar ID:nssv15888975, 4:10392422-10,402,191), were associated with uric acid levels (P = 5.23 × 10
and 2.29 × 10
, respectively). We also discovered a novel deletion spanning chromosome 18 (823 bp, dbVar ID: nssv15841628, 8:74347187-74,348,010) associated with low HDL cholesterol levels (P = 4.15 × 10
). Additionally, we observed two red blood cell traits-associated loci with genome-wide significance, a 13.2 kb deletion in 7q22.1 (nssv15922542) and a 3.7 kb deletion in 12q24.12 (nssv15813226), both of which were located in regions previously reported to be associated with red blood cell traits. Two deletions in 11q11 (nssv15803200 and nssv15802240), where clusters of multiple olfactory receptor genes exist, and a deletion (nssv15929560) upstream to DOCK5 were associated with childhood obesity. Finally, when defining Trait-Associated copy number Deletions (TADs) as CNDs with phenotype associations at sub-threshold significance (P < 10
), we identified 157 (97.5%) out of 161 TADs in non-coding regions, with a mean size of 4 kb (range: 209 - 47,942 bp).
We conducted a reanalysis of the UK10K Whole Genome Sequencing cohort, which led to the identification of multiple high confidence copy number deletions associated with quantitative traits. These deletions have standard dbVar IDs and replicate previous findings, as well as reveal novel loci that require further replication studies.
With the motivation of materializing a high-performance electrode material for the high-energy supercapacitor, ultrathin mesoporous graphitic‑carbon was synthesized from biomass green-tea wastes via ...the KOH activation process combined with either of the water or the hydrochloric acid treatment. The water-treated graphitic‑carbon showed an interconnected ultrathin-nanoflake structure with a high porosity, while the hydrochloric acid-treated graphitic carbon exhibited an aggregated structure of irregular nanoparticles. The supercapacitor with an electrode of water-treated graphitic‑carbon nanoflakes displayed an enhanced specific capacitance of 162F/g at 0.5 A/g. Furthermore, the device revealed an excellent cycle stability after multiple cyclic charge-discharge operations (i.e., 121% cyclic capacitance retention over 5000cycles). These may open up a new avenue toward the recycling of biomass carbonaceous resources (e.g., green tea wastes) for inexpensive high-performance electrochemical energy-storage devices such as high-energy supercapacitors.
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•Graphitic carbon was derived from green tea wastes via KOH activation in air.•The hydrolysis treatment resulted in the formation of graphitic-carbon nanoflakes.•Graphitic-carbon nanoflakes showed an interconnected structure with high porosity (i.e., pore volume ~ 0.4713cm3/g).•Graphitic-carbon nanoflakes played an excellent role as a supercapacitor electrode (i.e., specific capacitance ~ 162F/g).•The results render a prospective way to the recycling of biomass waste resources.
•The AC-CeO2 nanocomposites were prepared by the facile ultrasonication method.•AC-CeO2 showed an aggregated morphology with AC nanoflakes and CeO2 nanoparticles.•AC-CeO2 hybridization led to the ...increased charge separation of the photocarriers.•These lead to the highly-efficient photocatalytic CV dye-degradation activity.•AC-CeO2 can be of good use as an excellent photocatalyst for dye degradation.
Semiconductor-based photocatalysis is one of the favorable techniques for the wastewater treatment. Herein, we synthesized the activated carbon-decorated cerium dioxide (AC-CeO2) nanocomposites via the facile ultrasonication method by using the biomass-derived AC nanoflakes and the sonochemically-synthesized CeO2 nanoparticles. The AC-CeO2 nanocomposites exhibited the aggregated morphology with the AC nanoflakes-anchored CeO2 nanoparticles. Since the hybridization of conductive AC and semiconductive CeO2 would lead to the increased photocarrier transport and the reduced photocarrier recombination, during the photocatalytic reaction, the AC-CeO2 nanocomposites showed the enhanced crystal violet dye-degradation efficiency up to 97.9 % within 135 min. The results suggest that the AC-CeO2 nanocomposites hold promise as a prominent photocatalyst for future green environmental technology.
High-performance negative-differential transconductance (NDT) devices are fabricated in the form of a gated p
-i-n
Si ultra-thin body transistor. The devices clearly display a Λ-shape transfer ...characteristic (i.e., Λ-NDT peak) at room temperature, and the NDT behavior is fully based on the gate-modulation of the electrostatic junction characteristics along source-channel-drain. The largest peak-to-valley current ratio of the Λ-NDT peak is greater than 10
, the smallest full-width at half-maximum is smaller than 170 mV, and the best swing-slope at the Λ-NDT peak region is ~70 mV/dec. The position and the current level of the Λ-NDT peaks are systematically-controllable when modulating the junction characteristics by controlling only bias voltages at gate and/or drain. These unique features allow us to demonstrate the multivalue logic functions such as a tri-value logic and a quattro-value logic. The results suggest that the present type of the Si Λ-NDT device could be prospective for next-generation arithmetic circuits.
The hexagonal NiCo2S4 hierarchical nanostructure was nucleated on the reduced graphene oxide (rGO) sheets using a simple hydrothermal method for use it as an electrode material for supercapacitor ...applications. Benefiting the synergistic effects from the hierarchical architecture of NiCo2S4 and outstanding conductivity of rGO, the hybrid rGO-NiCo2S4 composites provided many advantages such as increased electrolyte diffusion pathways, fast electron transport, and ample active sites. Thus, the hybrid rGO-NiCo2S4 composites presented a higher specific capacitance (972 F/g), compared with bare NiCo2S4 (716 F/g), at the current density of 1 A/g. Using the prepared nanomaterials, the asymmetric supercapacitor devices were constructed in the form of the 2-electrodes scheme. Remarkably, the rGO-NiCo2S4 based device demonstrated the excellent energy-storage characteristics with a higher specific capacitance (208 F/g) than that of the bare NiCo2S4 based device (86 F/g). After 2000 cycles, the rGO-NiCo2S4 supercapacitor device revealed an excellent cyclic stability with 94.1% of the capacitance retention at the current density of 3 A/g. Moreover, hybrid rGO-NiCo2S4 showed an admirable catalytic activity for nitroarene reduction. These findings suggest that the prepared rGO-NiCo2S4 MOF can be served as an excellent bifunctional electrocatalyst for the high-performance supercapacitor and the nitroarene reduction applications.
Abstract
Whereas lifestyle-related factors are recognized as snoring risk factors, the role of genetics in snoring remains uncertain. One way to measure the impact of genetic risk is through the use ...of a polygenic risk score (PRS). In this study, we aimed to investigate whether genetics plays a role in snoring after adjusting for lifestyle factors. Since the effect of polygenic risks may differ across ethnic groups, we calculated the PRS for snoring from the UK Biobank and applied it to a Korean cohort. We sought to evaluate the reproducibility of the UK Biobank PRS for snoring in the Korean cohort and to investigate the interaction of lifestyle factors and genetic risk on snoring in the Korean population. In this study, we utilized a Korean cohort obtained from the Korean Genome Epidemiology Study (KoGES). We computed the snoring PRS for the Korean cohort based on the UK Biobank PRS. We investigated the relationship between polygenic risks and snoring while controlling for lifestyle factors, including sex, age, body mass index (BMI), alcohol consumption, smoking, physical activity, and sleep time. Additionally, we analyzed the interaction of each lifestyle factor and the genetic odds of snoring. We included 3526 snorers and 1939 nonsnorers from the KoGES cohort and found that the PRS, a polygenic risk factor, was an independent factor for snoring after adjusting for lifestyle factors. In addition, among lifestyle factors, higher BMI, male sex, and older age were the strongest lifestyle factors for snoring. In addition, the highest adjusted odds ratio for snoring was higher BMI (OR 1.98, 95% CI 1.76–2.23), followed by male sex (OR 1.54, 95% CI 1.28–1.86), older age (OR 1.23, 95% CI 1.03–1.35), polygenic risks such as higher PRS (OR 1.18, 95% CI 1.08–1.29), drinking behavior (OR 1.18, 95% CI 1.03–1.35), late sleep mid-time (OR 1.17, 95% CI 1.02–1.33), smoking behavior (OR 0.99, 95% CI 0.82–1.19), and lower physical activity (OR 0.92, 95% CI 0.85–1.00). Our study identified that the UK Biobank PRS for snoring was reproducible in the Korean cohort and that genetic risk served as an independent risk factor for snoring in the Korean population. These findings may help to develop personalized approaches to reduce snoring in individuals with high genetic risk.
In situ facile synthesis and the characterization of nanohydroxyapatite/chitosan (nHAP/CS) biocomposites were investigated for examining their potential applications in orthopedic implant technology. ...Firstly, the bare nHAP, europium-doped hydroxyapatite (Eu-nHAP), yttrium-doped hydroxyapatite (Y-nHAP), and Eu- and Y-codoped hydroxyapatite (Eu,Y-nHAP) nanoparticles were synthesized by the wet precipitation technique using biowaste-eggshell-derived calcium oxide powders. Then, through ultrasonication using the nanohydroxyapatite/chitosan mixtures (molar ratio = 1:2), the nHAP/CS, Eu-nHAP/CS, Y-nHAP/CS, and Eu,Y-nHAP/CS biocomposites were fabricated. Among them, Eu,Y-nHAP/CS showed higher cell viability (94.9%), higher solubility (pH = 7.6 after 21 days), and greater antibacterial activity than those of the other composites. In addition, Eu,Y-nHAP/CS exhibited improved mechanical properties compared with the other composites. For example, the nanoindentation test displayed the Eu,Y-nHAP/CS-coated 316L stainless steel implant to possess a higher Young's modulus value (9.24 GPa) and greater hardness value (300.71 MPa) than those of the others. The results indicate that the biomass-eggshell-derived Eu,Y-doped nHAP is of good use for orthopedic implant applications.
A sustainable and efficient electrocatalyst for the oxygen evolution reaction (OER) is vital to realize green and clean hydrogen production technology. Herein, we synthesized the nanocomposites of ...activated carbon-anchored nickel oxide (AC-NiO) via fully green routes, and characterized their excellent OER performances. The AC-NiO nanocomposites were prepared by the facile sonication method using sonochemically prepared NiO nanoparticles and biomass-derived AC nanosponges. The nanocomposites exhibited an aggregated structure of the AC-NiO nanotablets with an average size of 40 nm. When using the nanotablets as an OER catalyst in 1 M KOH, the sample displayed superb electrocatalytic performances, i.e., a substantially low value of overpotential (320 mV at 10 mA/cm
), a significantly small Tafel slope (49 mV/dec), and a good OER stability (4% decrease of overpotential after 10 h). These outstanding OER characteristics are considered as attributing to the synergetic effects from both the ample surface area of the electrochemically active NiO nanoparticles and the high electrical conductivity of the AC nanosponges. The results pronounce that the fully ecofriendly synthesized AC-NiO nanotablets can play a splendid role as high-performance electrocatalysts for future green energy technology.
Genomic and precision medicine research has afforded notable advances in human cancer treatment, yet applicability to other species remains uncertain. Through whole-exome and transcriptome analyses ...of 191 spontaneous canine mammary tumors (CMTs) that exhibit the archetypal features of human breast cancers, we found a striking resemblance of genomic characteristics including frequent PIK3CA mutations (43.1%), aberrations of the PI3K-Akt pathway (61.7%), and key genes involved in cancer initiation and progression. We also identified three gene expression-based CMT subtypes, one of which segregated with basal-like human breast cancer subtypes with activated epithelial-to-mesenchymal transition, low claudin expression, and unfavorable disease prognosis. A relative lack of ERBB2 amplification and Her2-enrichment subtype in CMT denoted species-specific molecular mechanisms. Taken together, our results elucidate cross-species oncogenic signatures for a better understanding of universal and context-dependent mechanisms in breast cancer development and provide a basis for precision diagnostics and therapeutics for domestic dogs.
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