CdS/TiO2 nano hybrid heterostructured materials for superior hydrogen production and gas sensor applications.

In efforts to minimize environmental pollution and carbon-based gas emissions, photocatalytic hydrogen production and sensing applications at ambient temperature are important. This research reports on the development of new 0D/1D materials based on TiO2 nanoparticles grown onto CdS hetersturctured nanorods via two-stage facile synthesis. The titanate nanoparticles when loaded onto CdS surfaces at an optimized concentration (20 mM), exhibited superior photocatalytic hydrogen production (21.4 mmol/h/gcat). The optimized nanohybrid was recycled for 6 cycles up to 4 h, indicating its excellent stabity for a prolonged period. Also, the photoelectrochemical water oxidation in alkaline medium was investigated to offer the optimized CRT-2 composite with 1.91 mA/cm2@0.8 V vs. RHE (0 V vs. Ag/AgCl) that was used for effective room-temperature NO2 gas detection exhibiting a higher response (69.16%) to NO2 (100 ppm) at room temperature at the lowest detection limit of ∼118 ppb than the pristine counterparts. Further, NO2 gas sensing performance of CRT-2 sensor was increased using UV light (365 nm) activation energy. Under the UV light, the sensor exhibited a remarkable gas sensing response quick response/recovery times (68/74), excellent long-term cycling stability, and significant selectivity to NO2 gas. Due to high porosity and surface area values of CdS (5.3), TiO2 (35.5), and CRT-2 (71.5 m2/g), excellent photocatalytic H2 production and gas sensing of CRT-2 is ascribed to morphology, synergistic effect, improved charge generation, and separation. Overall, 1D/0D CdS@TiO2 is proved to be an efficient material for hydrogen production and gas detection.

Pancreatic ductal adenocarcinoma with a predominant large duct pattern has better recurrence-free survival than conventional pancreatic ductal adenocarcinoma: a comprehensive histopathological, immunohistochemical, and mutational study.

Large duct pattern of pancreatic ductal adenocarcinomas (PDACs) comprises occasional large cancer glands (>0.5 mm in size), along with conventional smaller cancer glands. They histologically mimic intraductal papillary mucinous neoplasms. However, the clinicopathologic significance of PDACs with predominant large duct pattern (PLDP) has not been systematically evaluated. A total of 41 cases of PDACs with PLDP, which were defined as irregularly-shaped cancer glands >0.5 mm in size occupied >50% of tumor volume, were enrolled and their clinicopathological, immunohistochemical, and targeted exome-wise mutational characteristics were compared with 298 conventional PDACs. PDACs with PLDP had cancers with larger tumor sizes (P = 0.025), which were more frequently well to moderately differentiation (P < 0.001), with less lymphovascular invasion (P = 0.013) and had a higher T category (P = 0.023) than conventional PDACs. Immunohistochemically, PDACs with PLDP showed similar abnormal p53 (61%) and SMAD4 (59%) expression patterns as conventional PDACs. In addition, PDACs with PLDP showed diffuse MUC1 (88%), MUC5AC (100%), MUC6 (66%), and focal MUC2 (20%) expressions. More frequent ROS1 mutations were observed in PDACs with PLDP. PDAC patients with PLDP had a better overall and recurrence-free survival (OS and RFS; median, 42 and 34 months) than that of patients with conventional PDACs (34 and 16 months) as per univariate (P = 0.037 and P = 0.001) and multivariate (P = 0.031 and P = 0.034) analyses. PDACs with PLDP showed mutational patterns similar to those of conventional PDACs. They had unique histologic features and longer OS and RFS compared to those of conventional PDACs. Therefore, PDACs with PLDP could be considered a histologic subtype of PDACs.

Valorization of petroleum refinery oil sludges via anaerobic co-digestion with food waste and swine manure.

Valorization of oil sludge has been gaining attention to improve the sustainability of the petroleum industry. This study aimed to assess the possibility of anaerobic co-digestion of oil scum and secondary sludge with food waste (or swine manure). Oil scum and secondary sludge were obtained from a wastewater treatment plant (WWTP) of a petrochemical plant. Physicochemical properties, hazardous materials, and microbial community were characterized and biochemical methane potential was performed by a simplex-lattice mixture design. More than 87% (wet wt.) of the oil scum consisted of total petroleum hydrocarbons (TPHs) (21,762 mg/L) that are difficult to be degraded by anaerobes. The secondary sludge showed low TPHs (5 mg/L) and a bacterial community similar to that of municipal WWTPs. The heavy metal (Cu, As, Cr, Ni, Mn, Zn, and V) concentrations in the oil scum and secondary sludge were similar (20-600 mg/L). The maximum methane potentials of the oil sludge and secondary sludges were 20 ± 2 and 56 ± 3 mL CH4/g-volatile solid, respectively. The co-digestion with food waste or swine manure led to a synergy effect on methane production of the co-digestion substrate (10-40% increase compared to the calculated value; v/v) by balancing the C/N ratio. Due to the high TPH contents, oil scum is not appropriate for co-digestion. The co-digestion of secondary sludge with food waste and/or swine manure is recommended. It is necessary to consider whether the concentration of heavy metals is at a level that inhibits the anaerobic co-digestion depending on the operating conditions such as mixing ratios and solid contents.

Detection of Melanogenesis and Anti-Apoptosis-Associated Melanoma Factors: Array CGH and PPI Mapping Integrating Study.

BACKGROUND: We investigated melanogenesis- and anti-apoptosis-related melanoma factors in melanoma cells (TXM1, TXM18, A375P, and A375SM). OBJECTIVE: To find melanoma associated hub factor, high-throughput screening-based techniques integrating with bioinformatics were investigated. METHODS: Array CGH analysis was conducted with a commercial system. Total genomic DNAs prepared individually from each cell line with control DNA were properly labeled with Cy3-dCTP and Cy5-dCTP and hybridizations and subsequently performed data treatment by the log2 green (G; test) to red (R; reference) fluorescence ratios (G/R). Gain or loss of copy number was judged by spots with log2-transformed ratios. PPI mapping analysis of detected candidate genes based on the array CGH results was conducted using the human interactome in the STRING database. Energy minimization and a short Molecular Dynamics (MD) simulation using the implicit solvation model in CHARMM were performed to analyze the interacting residues between YWHAZ and YWHAB. RESULTS: Three genes (BMP-4, BFGF, LEF-1) known to be involved in melanogenesis were found to lose chromosomal copy numbers, and Chr. 6q23.3 was lost in all tested cell lines. Ten hub genes (CTNNB1, PEX13, PEX14, PEX5, IFNG, EXOSC3, EXOSC1, EXOSC8, UBC, and PEX10) were predicted to be functional interaction factors in the network of the 6q23.3 locus. The apoptosis-associated genes E2F1, p50, BCL2L1, and BIRC7 gained, and FGF2 lost chromosomal copy numbers in the tested melanoma cell lines. YWHAB, which gained chromosomal copy numbers, was predicted to be the most important hub protein in melanoma cells. Molecular dynamics simulations for binding YWHAB and YWHAZ were conducted, and the complex was predicted to be energetically and structurally stable through its 3 hydrogen-bond patterns. The number of interacting residues is 27. CONCLUSION: Our study compares genome-wide screening interactomics predictions for melanoma factors and offers new information for understanding melanogenesis- and anti-apoptosis-associated mechanisms in melanoma. Especially, YWHAB was newly detected as a core factor in melanoma cells.

Functional study of acetaldehyde dehydrogenase 1 (ALDH1) in keratinocytes: microarray integrating bioinformatics approaches.

The function of acetaldehyde dehydrogenase 1 (ALDH1) has been gradually elucidated in several diseases, especially in various cancers. However, the role of ALDH1 in skin-related diseases has been mostly unknown. Previously, we found that ALDH1 is involved in the pathogenesis of atopic dermatitis (AD). In this study, we used high-throughput screening (HTS) approaches to identify critical factors associated with ALDH1 in human keratinocytes to reveal its functions in skin. We overexpressed ALDH1 in human HaCaT keratinocytes and then conducted serial HTS studies, a DNA microarray and antibody array integrated with bioinformatics algorithms. Together, those tests identified several novel genes associated with the function of ALDH1 in keratinocytes, as well as AD, including CTSG and CCL11. In particular, GNB3, GHSR, TAS2R9, FFAR1, TAS2R16, CCL21, GPR32, NPFFR1, GPR15, FBXW12, CCL19, EDNRA, FFAR3, and RXFP3 proteins were consistently detected as hub proteins in the PPI maps. By integrating the datasets obtained from these HTS studies and using the strengths of each method, we obtained new insights into the functional role of ALDH1 in skin keratinocytes. The approach used here could contribute to the clinical understanding of ALDH1-associated applications for the treatment of AD.Communicated by Ramaswamy H. Sarma.

A Knock-Down Cell-Based Study for the Functional Analysis of Chloride Intracellular Channel 1 (CLIC1): Integrated Proteomics and Microarray Study.

BACKGROUND: Previously, we detected that chloride intracellular channel 1 (CLIC1) was involved in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: In this study, we aimed to use high-throughput screening (HTS) approaches to identify critical factors associated with the function of CLIC1 in knock-down cells. METHODS: We down-regulated CLIC1 in human A549 cells via siRNA and then conducted serial HTS studies, including proteomics integrated with a microarray and the implementation of bioinformatics algorithms. RESULTS: Together, these approaches identified several important proteins and genes associated with the function of CLIC1. These proteins and genes included tumor rejection antigen (gp96) 1, nucleophosmin, annexin I, keratin 1 and 10, FLNA protein, enolase 1, and metalloprotease 1, which were found using two-dimensional electrophoresis (2-DE) proteomics. Separately, NTNG1, SEMA5A, CLEC3A, GRPR, GNGT2, GRM5, GRM7, DNMT3B, CXCR5, CCL11, CD86, IL2, MNDA, TLR5, IL23R, DPP6, DLGAP1, CAT, GSTA1, GSTA2, GSTA5, CYP2E1, ADH1A, ESR1, ARRDC3, A1F1, CCL5, CASP8, DNTT, SQSTM1, PCYT1A, and SLCO4C1 were found using a DNA microarray integrated with PPI mapping. CONCLUSION: CCL11 is thought to be a particularly critical gene among the candidate genes detected in this study. By integrating the datasets and utilizing the strengths of HTS, we obtained new insights into the functional role of CLIC1, including the use of CLIC1-associated applications in the treatment of human diseases such as AD.

Tyrosinase-mediated melanogenesis in melanoma cells: Array comparative genome hybridization integrating proteomics and bioinformatics studies.

We investigated the tyrosinase-associated melanogenesis in melanoma cells by using OMICS techniques. We characterized the chromosome copy numbers, including Chr 11q21 where the tyrosinase gene is located, from several melanoma cell lines (TXM13, G361, and SK-MEL-28) by using array CGH. We revealed that 11q21 is stable in TXM13 cells, which is directly related to a spontaneous high melanin pigment production. Meanwhile, significant loss of copy number of 11q21 was found in G361 and SK-MEL-28. We further profiled the proteome of TXM13 cells by LC-ESI-MSMS and detected more than 900 proteins, then predicted 11 hub proteins (YWHAZ; HSP90AA1; HSPA5; HSPA1L; HSPA9; HSP90B1; HSPA1A; HSPA8; FKSG30; ACTB; DKFZp686DQ972) by using an interactomic algorithm. YWHAZ (25% interaction in the network) is thought to be a most important protein as a linking factor between tyrosinase-triggered melanogenesis and melanoma growth. Bioinformatic tools were further applied for revealing various physiologic mechanisms and functional classification. The results revealed clues for the spontaneous pigmentation capability of TXM13 cells, contrary to G361 and SK-MEL-28 cells, which commonly have depigmentation properties during subculture. Our study comparatively conducted the genome-wide screening and proteomic profiling integrated interactomics prediction for TXM13 cells and suggests new insights for studying both melanogenesis and melanoma.

An OMICS-based study of the role of C3dg in keratinocytes: RNA sequencing, antibody-chip array, and bioinformatics approaches.

Previously, we have identified the C3dg protein as an important player in the pathogenesis of atopic dermatitis (AD). In this study, we aimed to identify critical factors associated with C3dg in human keratinocytes based on high-throughput screening (HTS) approaches. We overexpressed C3dg in HaCaT human keratinocytes and conducted serial HTS studies, including RNA sequencing analysis integrated with antibody-chip arrays and implementation of bioinformatics algorithms (PPI mappings). Cumulatively, these approaches identified several novel C3dg-associated genes and proteins that are thought to be significantly involved in skin diseases including AD. These novel genes and proteins included LPA, PROZ, BLK, CLDN11, and FGF22, which are believed to play important roles in C3dg-associated skin functions in keratinocytes, as well as genes related to the two important pathways of systemic lupus erythematosus and Staphylococcus aureus infection. In particular, FGF22 is a unique gene that was detected and validated in all methods applied in this study. By integrating the datasets obtained from these HTS studies and utilizing the strengths of each method, we obtained new insights into the functional role of C3dg in keratinocytes. The approach used here contributes to clinical understanding of C3dg-associated applications and may also be applicable to treatment of AD.

Olmutinib Induced Lichen Planus Like Eruption.

Drug induced lichen planus like eruption is an uncommon cutaneous adverse effect of several drugs. This appears symmetric eruption of erythematous or violaceous plaques resembling lichen planus on the trunk and extremities. A 50-year-old male presented with scaly, violaceous plaques and dusky brown macules on whole body. For four months, the patient was treated with olmutinib, an oral, third-generation epidermal growth factor receptor-tyrosine kinase inhibitor. In May 2016, olmutinib received its first global approval in South Korea for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer. The biopsy specimen from the patient showed features of lichen planus. We diagnosed him with olmutinib-induced lichen planus like eruption. He was treated with oral methylprednisolone and topical desoxymethasone 0.25% ointment. At the same time, olmutinib dose was decreased to three-fourths of this patient's starting dose. After that, the cutaneous lesions improved.

Proteomic analyses for profiling regulated proteins/enzymes by Fucus vesiculosus fucoidan in B16 melanoma cells: A combination of enzyme kinetics functional study.

Fucoidans are complex sulfated polysaccharides that have a wide range of biological activities. Previously, we reported the various effects of Fucus vesiculosus fucoidan on tyrosinase and B16 melanoma cells. In this study, to identify fucoidan-targeted proteins in B16 melanoma cells, we performed a proteomics study and integrated enzyme kinetics. We detected 19 candidate proteins dysregulated by fucoidan treatment. Among the probed proteins, the enzyme kinetics of two candidate enzymes, namely lactate dehydrogenase (LDH) as an upregulated protein and superoxide dismutase (SOD) as a downregulated enzyme, were determined. The enzyme kinetics results showed that Fucus vesiculosus fucoidan significantly inhibited LDH catalytic function while it did not affect SOD activity even at a high dose, while only slightly decreased activity (up to 10%) at a low dose. Based on our previous and present observations, fucoidan could inhibit B16 melanoma cells growth via regulating proteins/enzymes expression levels such as LDH and SOD known as cell survival biomarkers. Interestingly, both expression level and enzyme catalytic activity of LDH were regulated by fucoidan, which could directly induce the apoptotic effect on B16 melanoma cells along with SOD downregulation. This study highlights how combining proteomics with enzyme kinetics can yield valuable insights into fucoidan targets.

Analysis of the peptides detected in atopic dermatitis and various inflammatory diseases patients-derived sera.

Serum proteomics has been applied for the discovery and analysis of biomarkers related to human disease. Serum is an optimal source to identify proteins derived from diseased-tissue compartments. We recently established an integrative method to analyze highly basic proteins that remain unresolved by the general 2D-PAGE method. In this follow-up study, we successfully detected several disease-associated proteins from sera samples obtained from patients with atopic dermatitis (AD). After proteomic analyses, target proteins were validated from AD patient-derived sera using ELISA or Western blotting methods We detected zinc finger CCHC domain containing 10 (ZCCHC10), peptidoglycan recognition protein L (PGRP-L), kininogen, α-1-antitrypsin, and hornerin proteins that are dysregulated in AD patient sera samples, which suggest effective approaches to methodologically analyze the serum proteome. Thus, the integrated proteomic method approach described here could be applicable for the detection of proteins associated with other human diseases. Our present study provides new insights into optimized serum proteomic techniques to understand systemic events of AD.

Computational prediction integrating the inhibition kinetics of gallotannin on α-glucosidase.

Due to the finding that inhibition of α-glucosidase is directly associated with treatment of several diseases, the development of a selective inhibitor for targeting α-glucosidase is important. Gallotannin (GT) is a natural ingredient that has been used as a food additive and for medicinal applications. In this study, we performed a computational docking experiment involving the pre-simulation of the binding mechanism of GT, and the effect of GT on α-glucosidase was evaluated with inhibitory kinetics based on its polyphenol properties. The computational simulations indicated that the hydroxyl groups of GT interact with several residues near the α-glucosidase active site (Met69, Tyr71, Phe177, Arg212, Asp214, Glu276, His348, Asp349, and Arg439), which could affect the catalytic function of α-glucosidase by retarding substrate access. Subsequent kinetic experiments showed that GT conspicuously inhibited α-glucosidase in a parabolic mixed-type manner (IC50=1.31±0.03µM;Ki=0.41±0.032µM). Our study provides insight into the inhibition mechanism and binding manner of GT to α-glucosidase. Based on its α-glucosidase-inhibiting effect and its demonstrated safety as a naturally derived compound, GT represents a promising potential agent for treatment of α-glucosidase-associated diseases.

Efficacy of Punch Reduction Prior to Cryotherapy in Patients with Viral Warts: A Case-Control Study in a Single Tertiary Center.

BACKGROUND: Cutaneous warts are a common complaint to visit dermatologic clinic and its course is variable, ranging from spontaneous resolution to a chronic condition refractory to treatment. OBJECTIVE: To evaluate the efficacy and safety of punch biopsy for cutaneous warts. METHODS: Thirty-nine patients who received punch biopsy for warts were reviewed through charts and photos. Among them, 15 were matched with cryotherapy-only controls in terms of size and location of the wart. We compared the number and cost of treatments between the two groups. RESULTS: Eleven of the total 39 patients were treated with cryotherapy in addition to punch biopsy and the average number of treatments was 4.1±3.3 (mean±standard deviation). In a case-control study, the ratio value of cost was 2.9±3.6 in the experimental group and was 5.9±4.1 in controls (p<0.05). CONCLUSION: Punch biopsies can decrease the number and cost of treatment by reducing the size of warts and inducing local inflammation to accelerate resolution. Therefore, punch reduction should be considered as a viable measure to treat warts.

Mutational profiling of acral melanomas in Korean populations.

The proportion of acral melanoma (AM) is much higher in Asian populations than in Caucasian populations. Although mutational profiles associated with AM have been discovered in Caucasian populations, knowledge of its genetic alterations in Asian populations is limited. To describe the molecular nature of AM in Korean patients, we performed mutational profiling of AM and matched normal tissues in patients. Fifty-one formalin-fixed paraffin-embedded AM samples and 32 matched pairs from patients' saliva DNA were analysed by next-generation sequencing. Only mutations confirmed via digital droplet PCR or in BRAF, KIT and NRAS, the most frequently altered cancer genes in cutaneous melanoma, were considered as positive. The relationship between mutational status and clinicopathological features were examined. Of the 47 AM patients screened, alteration of BRAF, NRAS and KIT genes was observed in 6.4%, 4.3% and 8.5%, respectively. We also tested matched normal tissues of patients to identify tumor-specific mutations. Examination of the mutational profile in a cohort of 28 primary melanomas and matched normal controls found BRAF mutations in two cases (7.1%), KIT mutations in three cases (10.7%) and CTNNB1 mutations in one case (3.6%). The BRAF, NRAS and KIT mutation status did not correlate with clinicopathological characteristics. Our results show that KIT, NRAS and BRAF hotspot mutations occur at a low frequency in Korean populations. We also observed a case with the CTNNB1 mutation, which raises the possibility that other pathways are associated with AM development.

Structural environment built by AKAP12+ colon mesenchymal cells drives M2 macrophages during inflammation recovery.

Macrophages exhibit phenotypic plasticity, as they have the ability to switch their functional phenotypes during inflammation and recovery. Simultaneously, the mechanical environment actively changes. However, how these dynamic alterations affect the macrophage phenotype is unknown. Here, we observed that the extracellular matrix (ECM) constructed by AKAP12+ colon mesenchymal cells (CMCs) generated M2 macrophages by regulating their shape during recovery. Notably, rounded macrophages were present in the linear and loose ECM of inflamed colons and polarized to the M1 phenotype. In contrast, ramified macrophages emerged in the contracted ECM of recovering colons and mainly expressed M2 macrophage markers. These contracted structures were not observed in the inflamed colons of AKAP12 knockout (KO) mice. Consequently, the proportion of M2 macrophages in inflamed colons was lower in AKAP12 KO mice than in WT mice. In addition, clinical symptoms and histological damage were more severe in AKAP12 KO mice than in WT mice. In experimentally remodeled collagen gels, WT CMCs drove the formation of a more compacted structure than AKAP12 KO CMCs, which promoted the polarization of macrophages toward an M2 phenotype. These results demonstrated that tissue contraction during recovery provides macrophages with the physical cues that drive M2 polarization.

Blastic Plasmacytoid Dendritic Cell Neoplasm: Analysis of Clinicopathological Feature and Treatment Outcome of Seven Cases.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), which is derived from the precursor of plasmacytoid dendritic cells, is a rare and highly aggressive hematologic malignancy. It has only recently been recognized as a distinct entity. BPDCN characteristically has a predilection for cutaneous involvement. OBJECTIVE: The aim of this study was to describe the clinical and pathological features of BPDCN, and to review the treatment courses to analyze the prognosis and the optimal therapeutic approach. METHODS: We retrospectively reviewed seven BPDCN cases registered in the Samsung Medical Center database between January 2010 and December 2014. RESULTS: The median age of the patients was 52 years (range, 18~79 years), and six patients were male. The clinical staging was as follows: skin (n=5), lymph node (n=6), bone marrow (n=4), and peripheral blood (n=2). The skin manifestations were bruise-like tumefaction (n=4), erythematous nodule (n=4), or multiple erythematous papules (n=1). The pathological evaluation revealed dense diffuse or nodular infiltration of neoplastic cells, which were positive for CD4, CD56, and CD123 in the immunohistochemical analysis. Six patients received multiagent chemotherapy as the first-line treatment, alone (n=4), or followed by stem cell transplantation (SCT, n=1) or concurrent radiotherapy (n=1). The median progression-free survival after the first-line treatment was 6 months (range, 2~12 months). CONCLUSION: Three different skin manifestations were observed, with pathological features analogous to each other. All patients who received chemotherapy without SCT achieved partial or complete response but experienced relapse. Furthermore, they showed various clinical courses irrelevant to the cutaneous involvement.