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Tritium is a radioisotope of hydrogen emitting low energy β-rays in disintegration to

The structural and dynamical properties of water confined in nanoporous silica with a pore diameter of 2.7 nm were investigated by performing large-scale molecular dynamics simulations using the reactive force field. The radial distribution function and diffusion coefficient of water were calculated, and the values at the center of the pore agreed well with experimental values for real water. In addition, the pore was divided into thin coaxial layers, and the average number of hydrogen bonds, hydrogen bond lifetime, and hydrogen bond strength were calculated as a function of the radial distance from the pore central axis. The analysis showed that hydrogen bonds involving silanol (Si-OH) have a longer lifetime, although the average number of hydrogen bonds per atom does not change from that at the pore center. The longer lifetime, as well as smaller diffusion coefficient, of these hydrogen bonds is attributed to their greater strength.

Background The American Joint Committee on Cancer (AJCC) 8th Edition Cancer Staging System was implemented in 2018; however, it has not been validated in an Asian melanoma population. Objective The purpose of this study was to validate the new system using a cohort of Japanese melanoma patients. Methods The AJCC 7th and 8th Editions were used for TNM classification of patients in a database established by the Japanese Melanoma Study Group. Patient data with sufficient information to be applicable to the AJCC 8th staging were selected. The Kaplan–Meier method was used to estimate disease-specific survival and relapse-free survival. Results In total, data for 3097 patients were analyzed. The 5-year disease-specific survival according to the 7th and 8th Edition staging system were as follows: IA = 98.5%/97.9%; IB = 95.4%/96.2%; IIA = 94.2%/94.1%; IIB = 84.6%/84.4%; IIC = 72.2%/72.2%; IIIA = 76.2%/87.5%; IIIB = 60.7%/72.6%; IIIC = 42.0%/55.3% and IIID = none/26.0%. The 5-year relapse-free survival according to the 7th and 8th Edition staging was as follows: IA = 94.5%/92.7%; IB = 85.4%/85.3%; IIA = 80.1%/79.4%; IIB = 71.4%/70.6%; IIC = 56.8%/55.7%; IIIA = 56.8%/69.4%; IIIB = 42.6%/56.8%; IIIC = 20.0%/33.3% and IIID = none/6.5%. Conclusion The results show that new staging system could efficiently classify our Japanese melanoma cohort. Although there was no difference in Stage I and II disease between the 7th and 8th Edition systems, we should be careful in managing Stage III disease since the survival curves of the 8th Edition staging were completely different from the 7th Edition. Moreover, our results indicate that adjuvant therapies for Stage IIB and IIC should be developed, since the relapse-free survival for these stages were equivalent to Stage IIIA and IIIB, respectively.

Background The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. Objectives To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. Methods Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. Results In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. Conclusions Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

We discover a new cavitation phenomenon in amorphous polymers sandwiched between two thick slide glasses from the static melt induced by thermal treatment. By quenching atactic polystyrene (aPS) samples from the static melt under the glass transition temperature (Tg) and annealing them above Tg for thick slide glasses, cavities are created to relax the negative pressure. Cavity growth undergoes an Ostwald ripening-like process in cases of large molecular weight, while it undergoes a viscous fingering process in cases of small molecular weight. The induction time for cavity formation is found to decrease with the increase of the annealing temperature and with the decrease of molecular weight. In contrast, no cavities are observed in an aPS sample between two thin cover glasses because the negative pressure can be relaxed by bending the whole thin cover glasses. We discover a new cavitation phenomenon in amorphous polymers sandwiched between two thick slide glasses from the static melt induced by thermal treatment. By quenching atactic polystyrene samples from the static melt under the glass transition temperature (Tg) and annealing them above Tg, cavities are created to relax the negative pressure. Cavity growth undergoes an Ostwald ripening-like process in cases of large molecular weight while it undergoes a viscous fingering process in cases of small molecular weight.

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We performed all-atom molecular dynamics simulations for bulk cyclohexane and analysed the short- and medium-range structures in supercooled and glassy states by using the Voronoi tessellation technique. From the analyses of both the potential energy of the system and the radial distribution function of molecules, cyclohexane was found to be vitrified as the temperature decreased. Furthermore, the icosahedral-like structures are dominant at all temperatures and grow in a supercooled liquid, whereas the face-centred cubic structures do not grow when the temperature decreases. It was also ascertained that the icosahedral-like structure is more dominant than the full-icosahedral one. The network of the distorted icosahedron spreads throughout the system at low temperatures. Our simulation demonstrates the stability of the icosahedral structure even in a non-spherical molecule such as cyclohexane., 12 pages, 7 figures

Accumulating evidence suggests that psoriasis is frequently accompanied by metabolic disorders, such as obesity and diabetes. However, the mechanisms underlying the association between increased psoriasis severity and concomitant metabolic syndrome have not been fully clarified. Herein, we show that imiquimod-induced psoriasiform inflammation was exacerbated and prolonged in diabetic obese mice compared to that in control mice, accompanied by remarkably increased lesional expressions of Cxcl5 and Il-1b. Notably, a large number of CXCL5+ Ly6G+ cells infiltrated the dermis and subcutaneous fat tissue of the diabetic obese mice. Most macrophages in the subcutaneous fat tissues of the diabetic obese mice were positive for expression of IL-1β and GRP78/Bip, an endoplasmic reticulum stress marker. Depletion of Ly6G+ cells and macrophages diminished the imiquimod-induced psoriasiform inflammation. Further, CXCL5 potentiated the secretion of IL-1β from macrophages and palmitic acid, a fatty acid released from subcutaneous adipocytes, further enhanced IL-1β secretion via endoplasmic reticulum stress induction. Combined with the fact that the serum levels of both CXCL5 and palmitic acid are significantly elevated in patients with metabolic syndrome, our results suggest a role for CXCL5 and endoplasmic reticulum stress in the increase of psoriasis severity of patients with concomitant metabolic syndrome.

The interleukin (IL)-23/IL-17 axis is strongly implicated in the pathogenesis of psoriasis. Previous studies showed that IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index. However, the mechanism whereby IL-18 affects disease severity remains unknown. In this study, we investigated the effects of IL-18 on a psoriasis-like skin inflammation model induced by recombinant mouse IL-23. We found that IL-18, cooperatively with IL-23, induced prominent inflammation and enhanced psoriasis-like epidermal hyperplasia. In the skin of mice treated with IL-23 plus IL-18, the expression of interferon-γ was significantly upregulated and that of chemokine (C-X-C motif) ligand 9 (CXCL9) was synergistically increased. Histologically, strong positive signals of CXCL9 were observed around the infiltrating inflammatory cells. The current results suggest that IL-18 might synergize with IL-23 to induce a T helper 1 immune reaction, without inhibiting the IL-23/IL-17 axis, and thus may aggravate psoriatic inflammation.

To investigate crystallinities based on trans-structures, we determined the differences in the crystallization properties of ring and linear polymers by performing united-atom-model molecular dynamics (MD) simulations of homogeneous polyethylene melts of equal length, N, which refers to the number of monomers per chain. Modified parameters based on the DREIDING force field for the CH2 units were used in order to accelerate the crystallization process. To detect polymer crystallization, we introduced some local-order parameters that relate to trans-segments in addition to common crystallinities using neighboring bond orders. Through quenching MD simulations at 5 K/ns, we roughly determined temperature thresholds, Tth, at which crystallization is observed although it was hard to determine the precise Tth as observed in the laboratory time frame with the present computing resources. When N was relatively small (100 and 200), Tth was determined to be 320 and 350 K for the linear- and ring-polyethylene melts, respectively, while Tth was found to be 330 and 350 K, respectively, when N was 1000. Having confirmed that the crystallization of a ring-polyethylene melt occurs faster than that of the analogous linear melt, we conclude that the trans-segment-based crystallinities are effective for the analysis of local crystal behavior.

DNA methylation is considered the primary epigenetic mechanism underlying the development of malignant melanoma. Since DNA methylation can be influenced by environmental factors, it is preferable to compare cancer and normal cells from the same patient. In order to compare the methylation status in melanoma tissues and melanocytes from the same individuals, we employed a novel epidermal sheet cultivation technique to isolate normal melanocytes from unaffected sites of melanoma patients. We also analyzed primary and metastatic melanoma samples, three commercially available melanocytes, and four melanoma cell lines. Cluster analysis of DNA methylation data classified freshly isolated melanomas and melanocytes into the same group, whereas the four melanoma cell lines were clustered together in a distant clade. Moreover, our analysis discovered methylation at several novel loci (KRTCAP3, AGAP2, ZNF490), in addition to those identified in previous studies (COL1A2, GPX3); however, the latter two were not observed in fresh melanoma samples. Subsequent studies revealed that NPM2 was hypermethylated and downregulated in melanomas, which was consistent with previous reports. In many normal melanocytes, NPM2 showed distinct immunohistochemical staining, while its expression was lost in malignant melanoma cells. In particular, intraepithelial lesions of malignant melanoma, an important challenge in clinical practice, could be distinguished from benign nevi. The present findings indicate the importance of using fresh melanoma samples, not melanoma cell lines and melanocytes in epigenetic studies. In addition, NPM2 immunoreactivity could be used to differentiate melanomas from normal melanocytes or benign disease.

The molecular mechanism of structural change caused by the beta-decay of substituted tritium on DNA or polymeric materials is still being unsolved and it is hard to study the decay effect of tritium solely by experiment. In order to study the structural changes of damaged polyethylene caused by the decay effect of tritium, we randomly removed hydrogen atoms from the polyethylene chain and performed molecular dynamics (MD) simulations using the reactive force field (ReaxFF). We adopted two parameter sets of ReaxFF and evaluated their reliability by comparing the atomic forces with density functional theory calculations. The results of MD simulations at a low temperature of 100 K show that the structure of polyethylene will be less ordered when losing more hydrogen atoms. It is observed that a double bond or a cyclic structure will be formed when two carbon atoms, which are the nearest or next-nearest neighbors, lose hydrogen atoms.

Using molecular dynamics (MD) simulation, we simulate the structural change of a telomeric DNA by β-decay of substituted tritium to helium-3. The configuration of the telomeric DNA is obtained by removing TRF2 protein from the TRF2-Dbd-DNA complex (Protein Data Bank ID is 3SJM). We assume that hydrogens (H) of guanines in the telomeric DNA are replaced to helium-3. Since this replacement of the H atoms to the 3He atoms changes the charge distribution significantly, the charge distribution used in the MD simulation for the modified guanine is obtained by the density functional theory calculations. We adopt, as the MD simulation, nanoscale molecular dynamics code with CHARMM36 force field using Langevin thermostat and Nosé–Hoover Langevin piston to control the temperature and pressure of the system, respectively. Moreover, changing both the number of replaced guanine N and the temperature of the system T, we calculate the root mean square deviation RMSD to quantify the dependence of the durability of the telomeric DNA on the β-decays. From the MD simulation, it is found that as N or T becomes larger, the RMSD of the DNA becomes also larger. Namely, it denotes that as the intensity of the β-decays becomes larger or as the temperature is increased, the DNA structure becomes more fragile.

The single-chain folding of an isotactic polypropylene (iPP) chain through united atom (UA) molecular dynamics simulations under quenching was investigated using force fields (FFs) based on TraPPE-UA. We estimated the degree of local rigidity of the folded chain along iPP undergoing single-chain folding. To maintain the tacticity of iPP, we introduced improper torsional angle potentials and/or explicit hydrogen atoms bonded to backbone carbon atoms. In the simulation using modified TraPPE-UA FFs with added hydrogen atoms, folded structures were observed. In the cases using modified TraPPE-UA FFs with only improper torsional potentials, folding of the quenched iPP chain was not observed. Moreover, to clarify the folding behavior of the iPP chain, we studied the chirality of a single iPP chain and subsequently observed spontaneous chirality selection during the quenched folding process. We also examined the effect of the angle and torsional potentials of the added hydrogen on the folding behavior of a single iPP chain into local crystals. Therefore, we confirmed that the strength of the angle and torsional potentials contributed to the acceleration of the folding behavior.

Fibroblastic connective tissue nevus (FCTN) is a benign cutaneous mesenchymal lesion characterized by proliferation of CD34-positive fibroblastic/myofibroblastic spindle-shaped cells. We report a case of agminated FCTN on the right lower abdomen of a 1-year-old boy.

Dipeptidyl peptidase-4 inhibitors are a new class of antidiabetic agents also shown to possess immunomodulatory functions. Although various dipeptidyl peptidase-4 inhibitors have been widely used and assumed to be administrated in many patients with psoriasis accompanied by type 2 diabetic mellitus, only two studies have shown that sitagliptin, a dipeptidyl peptidase-4 inhibitor, improved the cutaneous symptom of psoriasis independently of its antihyperglycemic effect. We report two cases of psoriatic skin lesions that obviously ameliorated after initiation of therapy with teneligliptin, a novel dipeptidyl peptidase-4 inhibitor. This report strengthens the notion that dipeptidyl peptidase-4 inhibitors clinically exert an ameliorating effect on psoriatic lesions. Considering the pharmacokinetic data that indicate the high penetrative ability of teneligliptin into skin tissue, teneligliptin may be considered an effective agent for improving skin lesions of psoriasis.

The melt memory of isotactic polystyrene spherulites from the melt is investigated using optical microscopy. When the melting–recrystallization processes are repeated by raising and lowering the temperature after the reset of the melt and the subsequent seeding process, the number of the spherulites is found to decrease with the cumulative melting time. The spherulites appear at the same positions as the original ones, and the higher the melt temperature is, the faster their number decreases. At the initial stage, the number density of spherulites rapidly decreases with the cumulative melting time. After the initial stage, the number density of spherulites exponentially decays with the cumulative melting time and approaches a finite value. This asymptotic value decreases with the melt temperature.

Diffusion dynamics of topological isomers of polymer molecules was investigated at the single-molecular level in the melt state by employing the fluorophore-incorporated 4-armed star and the corresponding doubly-cyclized, 8-shaped poly(THF) chains. While the single-molecule fluorescence imaging experiment revealed that the diffusion of the 4-armed star polymer was described by a single Gaussian distribution, the diffusion of the 8-shaped polymer exhibited a double Gaussian distribution behaviour. We reasoned that the two 8-shaped polymeric isomers have distinct diffusion modes in the melt state, although ensemble-averaged experimental methods cannot detect differences in the overall conformational state of the isomers. The single-molecule experiments suggested that one of the 8-shaped polymeric isomers, having the horizontally oriented form, causes an efficient threading with the linear matrix chains which leads to slower diffusion compared with the corresponding 4-armed star polymer, while the other 8-shaped polymeric isomer, having the vertically oriented form, displayed faster diffusion by the suppression of effective threading with the linear matrix chains due to its contracted chain conformation.

Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is a rare subtype of EBS that is characterized by blistering, mottled pigmentation of the trunk and limbs, punctate hyperkeratosis of the palms and soles, and dystrophic nails.(1) EBS-MP is caused by a mutation in the KRT5 or KRT14 gene encoding keratin 5 (K5) and keratin 14 (K14), respectively.(1, 2) Dermatopathia pigmentosa reticularis (DPR), caused by a KRT14 mutation, is characterized by reticulate pigmentation, noncicatricial alopecia, onychodystrophia and loss of dermatoglyphics.(3) Here, we report cases of EBS-MP with noncicatricial alopecia, a clinical feature of DPR, with a recurrent p.P25L mutation in KRT5 in four Japanese family members. This article is protected by copyright. All rights reserved.

Skin cancer incidence rates are continuing to rise; however, if detected at an early stage, they can be cured with minimally invasive treatment. Therefore, the identification of novel and robust biomarkers for the early detection of skin cancer is required to improve the quality of life of the patient after treatment. In the present study, we aimed to identify novel biomarkers of skin cancers. We carried out serum metabolomics using gas chromatography/triple quadrupole mass spectrometry for two types of skin cancer: squamous cell carcinoma and melanoma. The changes in the expression of metabolites compared with healthy volunteers were analyzed by principal component analysis. Among all 118 metabolites, 27 in patients with squamous cell carcinoma and 33 in patients with melanoma showed significant changes in comparison with healthy volunteers. Principal component analysis showed that both skin cancer groups could be distinguished from the healthy volunteers group. We further investigated the specific metabolites most useful for these distinctions. In the squamous cell carcinoma group, these metabolites were glycerol, 4-hydroxybenzoic acid, sebacic acid, fucose and suberic acid. In the melanoma group, these metabolites were glutamic acid, sebacic acid, suberic acid, 4-hydroxybenzoic acid and phenylalanine. The present study identified several metabolites that were distinct for certain skin cancer types, which could potentially be used as diagnostic biomarkers leading to novel clinical management strategies.

A pair of four-armed star and dicyclic 8-shaped poly(tetrahydrofuran)s, poly(THF)s, possessing a perylene diimide group at the core position (Ia and Ib, respectively) were synthesized by means of an electrostatic self-assembly and covalent fixation (ESA–CF) protocol. Mono- and bifunctional poly(THF)s having N-phenylpiperidinium salt end groups accompanying a perylene diimide tetracarboxylate as a counteranion were prepared by the ion-exchange reaction, and the subsequent covalent conversion by reflux in toluene afforded the corresponding core-fluorescent four-armed star and dicyclic 8-shaped poly(THF)s, (Ia and Ib, respectively) for the use of single-molecule fluorescence microscopy measurements.

Cytomegalovirus (CMV) is a DNA virus belonging to the Herpesviridae family, which causes various diseases with diverse symptoms, such as pneumonia, hepatitis, meningitis, retinitis, gastrointestinal ulcers, and cutaneous ulcers, especially in immunocompromised patients. CMV-related cutaneous ulcers often develop in the anogenital region and occasionally cause life-threatening complications. We report two patients with CMV-related cutaneous ulcers indicating an ominous clinical prognosis and severe [...]