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Abstract Background Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform. Methods The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment. Discussion This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers. Trial registration NCT05525858.

Abstract Objectives We performed comprehensive association analyses of common high-confidence gnomAD-reported copy number deletions (CNDs) with 60 quantitative traits from UK10K consortium WGS data. Methods 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

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.

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.

Background/Aims We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. Methods Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. Results RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. Conclusions NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

In pursuit of realizing neuromorphic computing devices, we demonstrated the high-performance synaptic functions on the top-to-bottom Au/ZnVO/Pt two-terminal ferroelectric Schottky junction (FSJ) device architecture. The active layer of ZnVO exhibited the ferroelectric characteristics because of the broken lattice-translational symmetry, arising from the incorporation of smaller V5+ ions into smaller Zn2+ host lattice sites. The fabricated FSJ devices displayed an asymmetric hysteresis behavior attributed to the ferroelectric polarization-dependent Schottky field-emission rate difference in between positive and negative bias voltage regions. Additionally, it was observed that the magnitude of the on-state current could be systematically controlled by changing either the amplitude or the width of the applied voltage pulses. Owing to these voltage pulse-tunable multi-state memory characteristics, the device revealed diverse synaptic functions such as short-term memory, dynamic range-tunable long-term memory, and versatile rules in spike time-dependent synaptic plasticity. For the pattern-recognition simulation, furthermore, more than 95% accuracy was recorded when using the optimized experimental device parameters. These findings suggest the ZnVO-based FSJ device holds significant promise for application in next-generation brain-inspired neuromorphic computing systems.

Abstract According to molecular profiling studies, a considerable number of patients with pancreatic cancer harbor potentially actionable mutations. However, there are limited relevant data from the Korean population. We assessed the molecular profiles of patients with pancreatic cancer in Korea. This study collected molecular profiling data from patients with pancreatic cancer who visited Seoul National University Bundang Hospital between March 2018 and August 2020. Formalin-fixed, paraffin-embedded tumor specimens were sequenced using a targeted next-generation sequencing (NGS) platform. Cancer-associated mutations were analyzed, and potentially actionable mutations were identified. Potentially actionable mutations were classified into “highly actionable” and “modifies options” based on the Know Your Tumor registry study. In total, 87 patients with NGS tumor panel data were identified. Sixty-one patients (70.1%) had metastatic disease at the time of tissue acquisition. Tissues were obtained from the primary tumors and metastatic sites in 41 (47.1%) and 46 (52.9%) patients, respectively. At least one pathogenic mutation was reported in 86 patients (98.9%). The frequencies of four common mutations in our cohort were similar to those in The Cancer Genome Atlas data. Potentially actionable mutations were identified in 27 patients (31.0%). Of these, mutations categorized as highly actionable and modifies options were identified in 12 (13.8%) and 18 patients (20.7%), respectively. The most frequent highly actionable mutations were located in DNA damage response genes, such as BRCA1, BRCA2, or ATM (n = 6, 6.9%). Two patients with germline BRCA1 mutations received maintenance poly(adenosine diphosphate-ribose) polymerase inhibitor therapy. One patient has been receiving maintenance treatment for 18 months while remaining in radiologically complete remission. Mutational profiles using targeted NGS in Korean patients with pancreatic cancer were similar to those in Western patients. The present study supports the clinical potential and possible expanded clinical use of genetic profiling.

Using the facile liquid-to-solid exfoliation method, the flexible Ag/2D-SnO/Au lateral memristor was fabricated onto the Ag and Au electrodes pre-patterned paper substrate. The asymmetric electrode system (i.e., Ag/2D-SnO/Au) could effectively lead to the electric field direction-dependent asymmetric hysteresis behavior, which is advantageous for explicit switching of the bistable ON/OFF states with a lower sneak current. Furthermore, the device exhibited the trustworthy data retention and the reliable endurance characteristics even under flex. These could be attributable to the sturdy filament networks formed along the multiple 2D SnO nanocrystallite domains (i.e., shunt-and-series nanoscale filaments). The method and the findings may provide an effective solution for the fabrication of the high-performance flexible lateral-memristor, which is of great benefit in future nanoelectronic information device technology.

We aimed to elucidate the evolutionary trajectories of gallbladder adenocarcinoma (GBAC) using multi-regional and longitudinal tumor samples. Using whole-exome sequencing data, we constructed phylogenetic trees in each patient and analyzed mutational signatures. A total of 11 patients including 2 rapid autopsy cases were enrolled. The most frequently altered gene in primary tumors was ERBB2 and TP53 (54.5%), followed by FBXW7 (27.3%). Most mutations in frequently altered genes in primary tumors were detectable in concurrent precancerous lesions (biliary intraepithelial neoplasia [BilIN]), but a substantial proportion was subclonal. Subclonal diversity was common in BilIN (n=4). However, among subclones in BilIN, a certain subclone commonly shrank in concurrent primary tumors. In addition, selected subclones underwent linear and branching evolution, maintaining subclonal diversity. Combined analysis with metastatic tumors (n=11) identified branching evolution in nine patients (81.8%). Of these, eight patients (88.9%) had a total of 11 subclones expanded at least sevenfold during metastasis. These subclones harbored putative metastasis-driving mutations in cancer-related genes such as SMAD4, ROBO1, and DICER1. In mutational signature analysis, six mutational signatures were identified: 1, 3, 7, 13, 22, and 24 (cosine similarity >0.9). Signatures 1 (age) and 13 (APOBEC) decreased during metastasis while signatures 22 (aristolochic acid) and 24 (aflatoxin) were relatively highlighted. Subclonal diversity arose early in precancerous lesions and clonal selection was a common event during malignant transformation in GBAC. However, selected cancer clones continued to evolve and thus maintained subclonal diversity in metastatic tumors.

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.

The transport characteristics of a gate-all-around Si multiple-quantum-dot (QD) transistor were studied by means of experimental parametrization using theoretical models. The device was fabricated by using the e-beam lithographically patterned Si nanowire channel, in which the ultrasmall QDs were self-created along the Si nanowire due to its volumetric undulation. Owing to the large quantum-level spacings of the self-formed ultrasmall QDs, the device clearly exhibited both Coulomb blockade oscillation (CBO) and negative differential conductance (NDC) characteristics at room temperature. Furthermore, it was also observed that both CBO and NDC could evolve along the extended blockade region within wide gate and drain bias voltage ranges. By analyzing the experimental device parameters using the simple theoretical single-hole-tunneling models, the fabricated QD transistor was confirmed as comprising the double-dot system. Consequently, based on the analytical energy-band diagram, we found that the formation of ultrasmall QDs with imbalanced energetic natures (i.e., imbalanced quantum energy states and their imbalanced capacitive-coupling strengths between the two dots) could lead to effective CBO/NDC evolution in wide bias voltage ranges.

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disease associated with a complex genetic etiology. Besides the apolipoprotein E ε4 (APOE ε4) allele, a few dozen other genetic loci associated with AD have been identified through genome-wide association studies (GWAS) conducted mainly in individuals of European ancestry. Recently, several GWAS performed in other ethnic groups have shown the importance of replicating studies that identify previously established risk loci and searching for novel risk loci. APOE-stratified GWAS have yielded novel AD risk loci that might be masked by, or be dependent on, APOE alleles. We performed whole-genome sequencing (WGS) on DNA from blood samples of 331 AD patients and 169 elderly controls of Korean ethnicity who were APOE ε4 carriers. Based on WGS data, we designed a customized AD chip (cAD chip) for further analysis on an independent set of 543 AD patients and 894 elderly controls of the same ethnicity, regardless of their APOE ε4 allele status. Combined analysis of WGS and cAD chip data revealed that SNPs rs1890078 (P = 6.64E−07) and rs12594991 (P = 2.03E−07) in SORCS1 and CHD2 genes, respectively, are novel genetic variants among APOE ε4 carriers in the Korean population. In addition, nine possible novel variants that were rare in individuals of European ancestry but common in East Asia were identified. This study demonstrates that APOE-stratified analysis is important for understanding the genetic background of AD in different populations.

Introduction Colorectal cancer (CRC) is one of the most deadly and common diseases in the world, accounting for over 881,000 casualties in 2018. The PTPRK-RSPO3 (P:R) fusion is a structural variation in CRC and well known for its ability to activate WNT signaling and tumorigenesis. However, till now, therapeutic targets and actionable drugs are limited in this subtype of cancer. Materials and method The purpose of this study is to identify key genes and cancer-related pathways specific for P:R fusion-positive CRC. In addition, we also inferred the actionable drugs in bioinformatics analysis using the Cancer Genome Atlas (TCGA) data. Results 2,505 genes were altered in RNA expression specific for P:R fusion-positive CRC. By pathway analysis based on the altered genes, ten major cancer-related signaling pathways (Apoptosis, Direct p53, EGFR, ErbB, JAK-STAT, tyrosine kinases, Pathways in Cancer, SCF-KIT, VEGFR, and WNT-related Pathway) were significantly altered in P:R fusion-positive CRC. Among these pathways, the most altered cancer genes (ALK, ACSL3, AXIN, MYC, TP53, GNAQ, ACVR2A, and FAS) specific for P:R fusion and involved in multiple cancer pathways were considered to have a key role in P:R fusion-positive CRC. Based on the drug-target network analysis, crizotinib, alectinib, lorlatinib, brigatinib, ceritinib, erdafitinib, infigratinib and pemigatinib were selected as putative therapeutic candidates, since they were already used in routine clinical practice in other cancer types and target genes of the drugs were involved in multiple cancer-pathways.

Comparison of spontaneous canine cancers and human cancers may illuminate future therapeutic avenues. Here, genomic analyses of these tumors highlights a convergence on PI3K-Akt oncogenic pathways.

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.

Carbonaceous materials play a vital role as an appropriate catalyst for electrocatalytic hydrogen production. Aiming at realizing the highly efficient hydrogen evolution reaction (HER), the partially graphitized activated-carbon nanobundles were synthesized as a high-performance HER electrocatalyst by using biomass human hair ashes through the high-temperature KOH activation at two different temperatures of 600 and 700 °C. Due to the partial graphitization, the 700 °C KOH-activated partially graphitized activated-carbon nanobundles exhibited higher electrical conductivity as well as higher textural porosity than those of the amorphous activated-carbon nanobundles that had been prepared by the KOH activation at 600 °C. As a consequence, the 700 °C-activated partially graphitized activated-carbon nanobundles showed the extraordinarily high HER activity with the very low overpotential (≈16 mV at 10 mA/cm2 in 0.5 M H2SO4) and the small Tafel slope (≈51 mV/dec). These results suggest that the human hair-derived partially graphitized activated-carbon nanobundles can be effectively utilized as a high-performance HER electrocatalyst in future hydrogen-energy technology.

The high-performance room-temperature-operating Si single-electron transistors (SETs) were devised in the form of the multiple quantum-dot (MQD) multiple tunnel junction (MTJ) system. The key device architecture of the Si MQD MTJ system was self-formed along the volumetrically undulated [110] Si nanowire that was fabricated by isotropic wet etching and subsequent oxidation of the e-beam-lithographically patterned [110] Si nanowire. The strong subband modulation in the volumetrically undulated [110] Si nanowire could create both the large quantum level spacings and the high tunnel barriers in the Si MQD MTJ system. Such a device scheme can not only decrease the cotunneling effect, but also reduce the effective electron temperature. These eventually led to the energetic stability for both the Coulomb blockade and the negative differential conductance characteristics at room temperature. The results suggest that the present device scheme (i.e., [110] Si MQD MTJ) holds great promise for the room-temperature demonstration of the high-performance Si SETs.

Genome-wide association studies of gastric cancer (GC) cases have revealed common gastric cancer susceptibility loci with low effect size. We investigated rare variants with high effect size via whole-exome sequencing (WES) of subjects with familial clustering of gastric cancer. WES of DNAs from the blood of 19 gastric cancer patients and 36 unaffected family members from 14 families with two or more gastric cancer patients were tested. Linkage analysis combined with association tests were performed using Pedigree Variant Annotation, Analysis, and Search Tool (pVAAST) software. Based on the logarithm of odds (LOD) and permutation-based composite likelihood ratio test (CLRT) from pVAAST, MUC4 was identified as a predisposing gene (LOD P-value = 1.9×10-5; permutation-based P-value of CLRT ≤ 9.9×10-9). In a larger cohort consisting of 597 GC patients and 9,759 healthy controls genotyped with SNP array, we discovered common variants in MUC4 regions (rs148735556, rs11717039, and rs547775645) significantly associated with GC supporting the association of MUC4 with gastric cancer. And the MUC4 variants were found in higher frequency in The Cancer Genome Atlas Study (TCGA) germline samples of patients with multiple cancer types. Immunohistochemistry indicated that MUC4 was downregulated in the noncancerous gastric mucosa of subjects with MUC4 germline missense variants, suggesting that loss of the protective function of MUC4 predisposes an individual to gastric cancer. Rare variants in MUC4 can be novel gastric cancer susceptibility loci in Koreans possessing the familial clustering of gastric cancer.

The biological behavior of sebaceous carcinoma (SeC) is relatively indolent; however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p < 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.

Some cancers with DNA mismatch repair deficiency display microsatellite instability. Here the authors analyse twenty three cancer types at the exome and whole-genome level, and identify loci with recurrent microsatellite instability that could be used to identify patients who would benefit from immunotherapy.

Abstract Somatic mutations in cancer genomes often show allelic imbalance (AI) of mutation abundance between the genome and transcriptome, but there is not yet a systematic understanding of AI. In this study, we performed large-scale DNA and RNA AI analyses of >100,000 somatic mutations in >2,000 cancer specimens across five tumor types using the exome and transcriptome sequencing data of the Cancer Genome Atlas consortium. First, AI analysis of nonsense mutations and frameshift indels revealed that nonsense-mediated decay is typical in cancer genomes, and we identified the relationship between the extent of AI and the location of mutations in addition to the well-recognized 50-nt rules. Second, the AI with splice site mutations may reflect the extent of intron retention and is frequently observed in known tumor suppressor genes. For missense mutations, we observed that mutations frequently subject to AI are enriched to genes related to cancer, especially those of apoptosis and the extracellular matrix, and C:G > A:T transversions. Our results suggest that mutations in known cancer-related genes and their transcripts are subjected to different levels of transcriptional or posttranscriptional regulation compared to wildtype alleles and may add an additional regulatory layer to the functions of cancer-relevant genes.

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 162 F/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 5000 cycles). 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. Keywords: Biomass resource, Green tea waste, Graphitic carbon, Nanoflakes, Electrode, Supercapacitor

High-quality silicon (Si) nanocrystals that simultaneously had superior mesoporous and luminescent characteristics were derived from sticky, red, and brown rice husks via the facile and cost-effective magnesiothermic reduction method. The Si nanocrystals were confirmed to comprise an aggregated morphology with spherical nanocrystals (e.g., average sizes of 15–50 nm). Due to the surface functional groups formed at the nanocrystalline Si surfaces, the Si nanocrystals clearly exhibited multiple luminescence peaks in visible-wavelength regions (i.e., blue, green, and yellow light). Among the synthesized Si nanocrystals, additionally, the brown rice husk (BRH)-derived Si nanocrystals showed to have a strong UV absorption and a high porosity (i.e., large specific surface area: 265.6 m2/g, small average pore diameter: 1.91 nm, and large total pore volume: 0.5389 cm3/g). These are indicative of the excellent optical and textural characteristics of the BRH-derived Si nanocrystals, compared to previously reported biomass-derived Si nanocrystals. The results suggest that the biomass BRH-derived Si nanocrystals hold great potential as an active source material for optoelectronic devices as well as a highly efficient catalyst or photocatalyst for energy conversion devices.

Among the various types of breast cancer, the luminal B subtype is the most common in young women, and ESR1-CCDC170 (E:C) fusion is the most frequent oncogenic fusion driver of the luminal B subtype. Nevertheless, treatments targeting E:C fusion has not been well established yet. Hence, the aim of this study is to investigate potential therapies targeting E:C fusion based on systematic bioinformatical analysis of the Cancer Genome Atlas (TCGA) data. One thousand related genes were extracted using transcriptome analysis, and major signaling pathways associated with breast cancer were identified with over-representation analysis. Then, we conducted drug-target network analysis based on the OncoKB and CIViC databases, and finally selected potentially applicable drug candidates. Six major cancer-related signaling pathways (p53, ATR/ATM, FOXM1, hedgehog, cell cycle, and Aurora B) were significantly altered in E:C fusion-positive cases of breast cancer. Further investigation revealed that nine genes (AURKB, HDAC2, PLK1, CENPA, CHEK1, CHEK2, RB1, CCNA2, and MDM2) in coordination with E:C fusion were found to be common denominators in three or more of these pathways, thereby making them promising gene biomarkers for target therapy. Among the 21 putative actionable drugs inferred by drug-target network analysis, palbociclib, alpelisib, ribociclib, dexamethasone, checkpoint kinase inhibitor AXD 7762, irinotecan, milademetan tosylate, R05045337, cisplatin, prexasertib, and olaparib were considered promising drug candidates targeting genes involved in at least two E:C fusion-related pathways.

The peculiar correlationship between the optical localization-state and the electrical deep-level defect-state was observed in the In0.52Al0.48As/In0.53Ga0.47As quantum well structure that comprises two quantum-confined electron-states and two hole-subbands. The sample clearly exhibited the Fermi edge singularity (FES) peak in its photoluminescence spectrum at 10–300 K; and the FES peak was analyzed in terms of the phenomenological line shape model with key physical parameters such as the Fermi energy, the hole localization energy, and the band-to-band transition amplitude. Through the comprehensive studies on both the theoretical calculation and the experimental evaluation of the energy band profile, we found out that the localized state, which is separated above by ~0.07 eV from the first excited hole-subband, corresponds to the deep-level state, residing at the position of ~0.75 eV far below the conduction band (i.e., near the valence band edge).

Although American Thyroid Association guidelines offer a risk stratification scheme for thyroid cancer patients, there is a continuous need for more sophisticated biomarkers that can predict disease progression. In this study, we aim to evaluate the prognostic value of class III beta-tubulin (TUBB3) and uncover the relationship between TUBB3 and invasive potential in thyroid carcinoma. Immunohistochemistry (IHC) for TUBB3 and E-cadherin was performed on a total of 254 cases of thyroid cancer specimens. Tumor budding at the invasive margin was evaluated. In vitro functional studies were also performed; the protein and mRNA levels of TUBB3 were compared among the five cell types at baseline, with transwell invasion and after blocking of TUBB3 by shRNA. IHC revealed that the levels of TUBB3 were higher in conventional papillary carcinomas (cPTCs) and anaplastic thyroid carcinomas (ATCs). In univariate analysis, high tumor budding and TUBB3 expression were associated with inferior progression-free survival in cPTC. The results of a Western blot and RT-PCR agreed with the IHC finding. The results were further validated through data from The Cancer Genome Atlas database. Our results suggest that high expression of TUBB3 in thyroid carcinoma could predict invasive potential and possibly be linked with epithelial–mesenchymal transition.

Aiming at materializing an excellent anodic source material of the high-performance sodium-ion battery (SIB), we fabricated the biomass carbon-silicon (C-Si) nanocomposites by the one-pot synthesis of facile magnesiothermic reduction using brown rice husk ashes. The C-Si nanocomposites displayed an aggregated morphology, where the spherical Si nanoparticles (9 nm on average) and the C nanoflakes were encapsulated and decorated with each other. When utilizing the nanocomposites as an SIB anode, a high initial discharge capacity (i.e., 378 mAh/g at 100 mA/g) and a high reversible capacity (i.e., 122 mAh/g at 200 mA/g) were achieved owing to their enhanced electronic and ionic conductivities. Moreover, the SIB device exhibited a high cyclic stability in its Coulombic efficiency (i.e., 98% after 100 charge-discharge cycles at 200 mA/g). These outstanding results depict that the one-pot synthesized biomass C-Si nanocomposites are beneficial for future green energy-storage technology.

In the present work, we demonstrated the upcycling technique of effective wastewater treatment via photocatalytic hydrogen production by using the nanocomposites of manganese oxide-decorated activated carbon (MnO2-AC). The nanocomposites were sonochemically synthesized in pure water by utilizing MnO2 nanoparticles and AC nanoflakes that had been prepared through green routes using the extracts of Brassica oleracea and Azadirachta indica, respectively. MnO2-AC nanocomposites were confirmed to exist in the form of nanopebbles with a high specific surface area of ~109 m2/g. When using the MnO2-AC nanocomposites as a photocatalyst for the wastewater treatment, they exhibited highly efficient hydrogen production activity. Namely, the high hydrogen production rate (395 mL/h) was achieved when splitting the synthetic sulphide effluent (S2− = 0.2 M) via the photocatalytic reaction by using MnO2-AC. The results stand for the excellent energy-conversion capability of the MnO2-AC nanocomposites, particularly, for photocatalytic splitting of hydrogen from sulphide wastewater.

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/cm2), 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.

The highly sensitive ultra-violet (UV) photodiode was demonstrated on the organic-inorganic hybrid heterostructure of β-phase p-type polyfluorene (PFO)/n-type yttrium-doped zinc oxide nanorods (YZO-NRs). The device was fabricated through a simple fabrication technique of β-phase PFO coating onto YZO-NRs that had been directly grown on graphene by the hydrothermal synthesis method. Under UV illumination (λ = 365 nm), the device clearly showed excellent photoresponse characteristics (e.g., high quantum efficiency ~690%, high photodetectivity ~3.34 × 1012 cm·Hz1/2·W−1, and fast response time ~0.17 s). Furthermore, the ratio of the photo current-to-dark current exceeds 103 even under UV illumination with a small optical power density of 0.6 mW/cm2. We attribute such superb photoresponse characteristics to both Y incorporation into YZO-NRs and conformation of β-phase PFO. Namely, Y dopants could effectively reduce surface states at YZO-NRs, and β-phase PFO might increase the photocarrier conductivity in PFO. The results suggest that the β-phase p-PFO/n-YZO-NR hybrid heterostructure holds promise for high-performance UV photodetectors.

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although early diagnosis and treatment is the most successful strategy for improving patient survival, feasible and sensitive blood biomarkers for CRC screening remain elusive. Methods: Sixty-five CRC patients and thirty-three healthy individuals were enrolled. Peripheral blood (PB) and tumor tissues from CRC patients, and PB from healthy individuals were subjected to immunophenotyping and phospho-flow analysis of cytokine-induced phosphorylated STAT (CIPS). Logistic regression was used as a classifier that separates CRC patients from healthy individuals. Results: The proportion of regulatory T cells was increased in PB from CRC patients compared to PB from healthy individuals (p < 0.05). Interestingly, peripheral T cells share several cytokine-induced phosphorylated STAT (CIPS) signatures with T cells from CRC tumor-sites. Additionally, a classifier was made using two signatures distinct between T cells from CRC patients and T cells from healthy individuals. The AUCs (area under curves) of the classifier were 0.88 in initial cohort and 0.94 in the additional validation cohort. Overall AUC was 0.94 with sensitivity of 91% and specificity of 88%. Conclusion: This study highlights that immune cell signatures in peripheral blood could offer a new type of biomarker for CRC screening.

The nanocomposites of activated-carbon-decorated silicon nanocrystals (ACAC) were synchronously derived in a single step from biomass rice husks, through the simple route of the calcination method together with the magnesiothermic reduction process. The final product, ACAC, exhibited an aggregated structure of activated-carbon-encapsulated nanocrystalline silicon spheres, and reveals a high specific surface area (498.5 m2/g). Owing to the mutualization of advantages from both silicon nanocrystals (i.e., low discharge potential and high specific capacity) and activated carbon (i.e., high porosity and good electrical conductivity), the ACAC nanocomposites are able to play a substantial role as an anodic source material for the lithium-ion battery (LIB). Namely, a high coulombic efficiency (97.5%), a high discharge capacity (716 mAh/g), and a high reversible specific capacity (429 mAh/g after 100 cycles) were accomplished when using ACAC as an LIB anode. The results advocate that the simultaneous synthesis of biomass-derived ACAC is beneficial for green energy-storage device applications.

Biomass-derived carbonaceous constituents constitute fascinating green technology for electrochemical energy-storage devices. In light of this, interconnected mesoporous graphitic carbon nanoflakes were synthesized by utilizing waste green-tea powders through the sequential steps of air-assisted carbonization, followed by potassium hydroxide activation and water treatment. Green-tea waste-derived graphitic carbon displays an interconnected network of aggregated mesoporous nanoflakes. When using the mesoporous graphitic carbon nanoflakes as an anode material for the lithium-ion battery, an initial capacity of ~706 mAh/g and a reversible discharge capacity of ~400 mAh/g are achieved. Furthermore, the device sustains a large coulombic efficiency up to 96% during 100 operation cycles under the applied current density of 0.1 A/g. These findings depict that the bio-generated mesoporous graphitic carbon nanoflakes could be effectively utilized as a high-quality anode material in lithium-ion battery devices.

The low-power, high-performance graphene/ZnO Schottky photodiodes were demonstrated through the direct sputter-growth of ZnO onto the thermally-cleaned graphene/SiO2/Si substrate at room temperature. Prior to the growth of ZnO, a thermal treatment of the graphene surface was performed at 280 °C for 10 min in a vacuum to desorb chemical residues that may serve as trap sites at the interface between graphene and ZnO. The device clearly showed a rectifying behavior with the Schottky barrier of ≈0.61 eV and an ideality factor of 1.16. Under UV illumination, the device exhibited the excellent photoresponse characteristics in both forward and reverse bias regions. When illuminating UV light with the optical power density of 0.62 mW/cm2, the device revealed a high on/off current ratio of >103 even at a low bias voltage of 0.1 V. For the transient characteristics upon switching of UV light pulses, the device represented a fast and stable photoresponse (i.e., rise time: 0.16 s, decay time: 0.19 s). From the temperature-dependent current−voltage characteristics, such an outstanding photoresponse characteristic was found to arise from the enhanced Schottky barrier homogeneity via the thermal treatment of the graphene surface. The results suggest that the ZnO/graphene Schottky diode holds promise for the application in high-performance low-power UV photodetectors.

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration. [ABSTRACT FROM AUTHOR]