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Abstract This study aims to elucidate the clinical and molecular characteristics, treatment outcomes and prognostic factors of patients with histone H3 K27-mutant diffuse midline glioma. We retrospectively analyzed 93 patients with diffuse midline glioma (47 thalamus, 24 brainstem, 12 spinal cord and 10 other midline locations) treated at 24 affiliated hospitals in the Kansai Molecular Diagnosis Network for CNS Tumors. Considering the term “midline” areas, which had been confused in previous reports, we classified four midline locations based on previous reports and anatomical findings. Clinical and molecular characteristics of the study cohort included: age 4–78 years, female sex (41%), lower-grade histology (56%), preoperative Karnofsky performance status (KPS) scores ≥ 80 (49%), resection (36%), adjuvant radiation plus chemotherapy (83%), temozolomide therapy (76%), bevacizumab therapy (42%), HIST1H3B p.K27M mutation (2%), TERT promoter mutation (3%), MGMT promoter methylation (9%), BRAF p.V600E mutation (1%), FGFR1 mutation (14%) and EGFR mutation (3%). Median progression-free and overall survival time was 9.9 ± 1.0 (7.9–11.9, 95% CI) and 16.6 ± 1.4 (13.9–19.3, 95% CI) months, respectively. Female sex, preoperative KPS score ≥ 80, adjuvant radiation + temozolomide and radiation ≥ 50 Gy were associated with favorable prognosis. Female sex and preoperative KPS score ≥ 80 were identified as independent good prognostic factors. This study demonstrated the current state of clinical practice for patients with diffuse midline glioma and molecular analyses of diffuse midline glioma in real-world settings. Further investigation in a larger population would contribute to better understanding of the pathology of diffuse midline glioma.

Dense tantalum-based carbonitride materials featuring >95 % relative density, TaC, Ta2C1.5N0.5, Ta2CN, Ta2C0.5N1.5 and TaN, were prepared by Spark Plasma Sintering (SPS) at 1873 K with a dwell time of 10 min and a pressure of 50 MPa. Despite the presence of an oxide phase (i.e. 5 vol%) and some W inclusions (i.e. 1 vol%), the mechanical properties of such ultra-high temperature ceramics (UHTC) show promising values. Indeed, the Young's moduli measured by nano-indentation were approx. 600–700 GPa, which is higher than literature values reported for similar UHTC. The hardness values increased from 16.4 ± 0.8 GPa for TaC to 27.9 ± 1.3 GPa for TaN, with an approximately linear trend for the carbonitride samples while the ratio of plastic deformation work over the total indentation work followed the opposite trend.

Abstract Background This study aimed to elucidate the impact of effective diffusion time setting on apparent diffusion coefficient (ADC)-based differentiation between primary central nervous system lymphomas (PCNSLs) and glioblastomas (GBMs) and to investigate the usage of time-dependent diffusion magnetic resonance imaging (MRI) parameters. Methods A retrospective study was conducted involving 21 patients with PCNSLs and 66 patients with GBMs using diffusion weighted imaging (DWI) sequences with oscillating gradient spin-echo (Δeff = 7.1 ms) and conventional pulsed gradient (Δeff = 44.5 ms). In addition to ADC maps at the two diffusion times (ADC7.1 ms and ADC44.5 ms), we generated maps of the ADC changes (cADC) and the relative ADC changes (rcADC) between the two diffusion times. Regions of interest were placed on enhancing regions and non-enhancing peritumoral regions. The mean and the fifth and 95th percentile values of each parameter were compared between PCNSLs and GBMs. The area under the receiver operating characteristic curve (AUC) values were used to compare the discriminating performances among the indices. Results In enhancing regions, the mean and fifth and 95th percentile values of ADC44.5 ms and ADC7.1 ms in PCNSLs were significantly lower than those in GBMs (p = 0.02 for 95th percentile of ADC44.5 ms, p = 0.04 for ADC7.1 ms, and p

Abstract Background This study was designed to investigate the use of time-dependent diffusion magnetic resonance imaging (MRI) parameters in distinguishing between glioblastomas and brain metastases. Methods A retrospective study was conducted involving 65 patients with glioblastomas and 27 patients with metastases using a diffusion-weighted imaging sequence with oscillating gradient spin-echo (OGSE, 50 Hz) and a conventional pulsed gradient spin-echo (PGSE, 0 Hz) sequence. In addition to apparent diffusion coefficient (ADC) maps from two sequences (ADC50Hz and ADC0Hz), we generated maps of the ADC change (cADC): ADC50Hz − ADC0Hz and the relative ADC change (rcADC): (ADC50Hz − ADC0Hz)/ ADC0Hz × 100 (%). Results The mean and the fifth and 95th percentile values of each parameter in enhancing and peritumoral regions were compared between glioblastomas and metastases. The area under the receiver operating characteristic curve (AUC) values of the best discriminating indices were compared. In enhancing regions, none of the indices of ADC0Hz and ADC50Hz showed significant differences between metastases and glioblastomas. The mean cADC and rcADC values of metastases were significantly higher than those of glioblastomas (0.24 ± 0.12 × 10−3mm2/s vs. 0.14 ± 0.03 × 10−3mm2/s and 23.3 ± 9.4% vs. 14.0 ± 4.7%; all p

Janus monolayers of transition metal dichalcogenides (TMDCs) are promising building blocks for moiré superlattices because of their built‐in electric field and clean fabrication process. In particular, Janus TMDC monolayers can be chemically converted from conventional TMDC monolayers by atomic substitution, enabling the direct formation of lattice‐mismatched heterobilayers from TMDC bilayers. However, the moiré superlattices of Janus heterobilayers have not been studied experimentally. Herein, this work reports the fabrication and characterization of semiconductor moiré superlattices in chemically tailored Janus heterobilayers. The MoSSe/MoSe2 (or WSSe/WSe2) Janus heterobilayers are prepared by replacing the top layer Se atoms with S atoms in MoSe2 (or WSe2) bilayer using H2 plasma treatment. Scanning transmission electron microscopy reveals that an average moiré period of about 14 nm formed due to lattice mismatch resulting from the chalcogen substitutions. The cryogenic photoluminescence spectra show sharp, near‐infrared emissions, which are attributed to excitons trapped by moiré potentials based on comparison with theoretical calculations. The Janus‐based heterostructures provide a long‐period moiré system with built‐in potential even for nontwisted heterobilayers, allowing the functionalization of confined and correlated electron systems.

Abstract Voltage‐gated K+ (KV) and Ca2+‐activated K+ (KCa) channels are essential proteins for membrane repolarization in excitable cells. They also play important physiological roles in non‐excitable cells. Their diverse physiological functions are in part the result of their auxiliary subunits. Auxiliary subunits can alter the expression level, voltage dependence, activation/deactivation kinetics, and inactivation properties of the bound channel. KV and KCa channels are activated by membrane depolarization through the voltage‐sensing domain (VSD), so modulation of KV and KCa channels through the VSD is reasonable. Recent cryo‐EM structures of the KV or KCa channel complex with auxiliary subunits are shedding light on how these subunits bind to and modulate the VSD. In this review, we will discuss four examples of auxiliary subunits that bind directly to the VSD of KV or KCa channels: KCNQ1–KCNE3, Kv4‐DPP6, Slo1‐β4, and Slo1‐γ1. Interestingly, their binding sites are all different. We also present some examples of how functionally critical binding sites can be determined by introducing mutations. These structure‐guided approaches would be effective in understanding how VSD‐bound auxiliary subunits modulate ion channels.

Summary: In mammals, kisspeptin (Kiss1) neurons are generally considered as a sex steroid-dependent key regulator of hypothalamic-pituitary-gonadal (HPG) axis. In contrast, previous studies in non-mammalian species, especially in teleosts, propose that Kiss1 is not directly involved in the HPG axis regulation, which suggests some sex-steroid-dependent functions of kisspeptin(s) other than the HPG axis regulation in non-mammals.Here, we used knockout (KO) medaka of kisspeptin receptor-coding genes (gpr54-1 and gpr54-2) and examined possible roles of kisspeptin in the regulation of sexual behaviors. We found that the KO pairs of gpr54-1, but not gpr54-2, spawned fewer eggs and exhibited delayed spawning than wild type pairs. Detailed behavior analysis suggested that the KO females are responsible for the delayed spawning and that the KO males showed hyper-motivation for courtship. Taken together, the present finding suggests that one of the reproductive-state-dependent functions of the Kiss1 may be the control of successful sexual behaviors.

Sebocytes express Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), which participate in the innate immune response of the skin. Although the roles of TLRs and NLR family pyrin domain-containing 3 (NLRP3) in inflammatory responses in sebocytes have been reported, the expression and functions of other NLR members, such as NOD protein-1 and -2 (NOD1 and NOD2, respectively), remain unclear. In this study, we showed that, in sebocytes, the expression of NOD1 is higher than that of NOD2, and that NOD1 is involved in inflammatory responses, such as the secretion of proinflammatory cytokines. A NOD1 agonist, L-alanyl-γ-D-glutamyl-meso-diaminopimelic acid (Tri-DAP) induced the expression and secretion of interleukin-8 (IL-8) and activated the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. On the other hand, a NOD2 agonist, muramyl dipeptide, did not. Either inhibition with a NOD1 inhibitor, ML130, or knockdown of NOD1 expression abolished Tri-DAP-induced inflammatory responses, suggesting that NOD1 is involved in the immunogenic signaling system of sebocytes. Furthermore, Tri-DAP and an agonist of TLR2 or TLR4 additively increased IL-8 expression compared with each agonist alone. Our results reveal the role of NOD1 in the inflammatory responses of sebocytes and may provide a novel therapeutic target for sebaceous gland inflammatory diseases, such as acne vulgaris.