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Abstract: In this paper, we present planar mesa termination structure with high k dielectric Al2O3 for high-voltage diamond Schottky barrier diode. Analysis, design, and optimization are carried out by simulations using finite element technology computer-aided design (TCAD) Sentaurus Device software. The performances of planar mesa termination structure are compared to those of conventional field plate termination structure. It is found that optimum geometry of planar mesa terminated diode requires shorter metal plate extension (1/3 of the field plate terminated diode). Consequently, planar mesa terminated diode can be designed with bigger Schottky contact to increase its current carrying capability. Breakdown performance of field plate termination structure is limited at 1480V due to peak electric field at the corner of Schottky contact (no oxide breakdown occurs). In contrast, peak electric field in planar mesa termination structure only occurs in the field oxide such that its breakdown performance is highly dependent on the oxide material. Due to Al2O3 breakdown, planar mesa termination structure suffers premature breakdown at 1440V. Considering no oxide breakdown occurs, planar mesa termination structure can realize higher breakdown voltage of 1751V. Therefore, to fully realize the potential of planar mesa terminated diode, it is important to choose suitable high k dielectric material with sufficient breakdown electric field for the field oxide. [Copyright &y& Elsevier]

Abstract: In this study, we investigated non-ideal characteristics of a diamond Schottky barrier diode with Molybdenum (Mo) Schottky metal fabricated by Microwave Plasma Chemical Vapour Deposition (MPCVD) technique. Extraction from forward bias I–V and reverse bias C −2–V measurements yields ideality factor of 1.3, Schottky barrier height of 1.872eV, and on-resistance of 32.63mΩ·cm2. The deviation of extracted Schottky barrier height from an ideal value of 2.24eV (considering Mo workfunction of 4.53eV) indicates Fermi level pinning at the interface. We attributed such non-ideal behavior to the existence of thin interfacial layer and interface states between metal and diamond which forms Metal-Interfacial layer-Semiconductor (MIS) structure. Oxygen surface treatment during fabrication process might have induced them. From forward bias C–V characteristics, the minimum thickness of the interfacial layer is approximately 0.248nm. Energy distribution profile of the interface state density is then evaluated from the forward bias I–V characteristics based on the MIS model. The interface state density is found to be uniformly distributed with values around 1013 eV−1·cm−2. [Copyright &y& Elsevier]

Abstract: The microscopic surface morphology of “lifted-off” surfaces, produced via ion implantation was observed by atomic force microscopy. A polished single-crystal diamond substrate with an average surface roughness of less than 0.1nm was used for precise observations. After the lift-off process, the lifted-off surface became rough with pits appearing. Hydrogen plasma treatment close to the chemical vapor deposition conditions for diamond (1150°C, 160Torr) completely removed these pits and the surface was subsequently covered by a strip-like structure consisting of atomic steps. The surface roughness, however, was not further influenced by the plasma treatment. The observed morphological evolution reflects the graphite/diamond interface formed by the lift-off. [Copyright &y& Elsevier]

Abstract: Thick (∼100μm) undoped diamond films were grown homoepitaxially on single crystal (SC) diamond substrates by microwave plasma chemical vapor deposition (CVD). To form a freestanding SC diamond film (plate), the substrate was pre-ion-implanted with high-energy ion beams before the film growth, and after the thick-film deposition, the substrate was eliminated using a lift-off method, resulting in fabrication of a SC CVD diamond plate. Two samples were prepared; sample 1 was grown on a (001) oriented, nitrogen doped CVD SC diamond at ∼900°C with the input microwave power of 1.7kW, while sample 2 was grown on a (001) oriented, high-pressure high-temperature synthesized type-Ib SC diamond at ∼900°C with the input microwave power of 1.25kW. The formed SC plates have high optical transparencies, indicating no remarkable optical absorptions seen in the wavelength from ultraviolet to near infrared. The photoluminescence (PL) spectra of both samples show strong free exciton FE peaks, while in sample 2 relatively strong optical emissions corresponding to nitrogen related centers were observed in the visible region. After the metal electrodes were formed on both faces of the SC diamond plate to fabricate a sandwich-type diamond particle detector, the energy spectra of 5.486MeV α-particles from 241Am were measured. The charge collection efficiencies (CCEs) of sample 1 were CCE=98% for a hole transport and CCE=89% for an electron transport, respectively, while CCEs of sample 2 were CCE=80% for a hole transport and CCE=78% for an electron transport, respectively. These results indicate that both holes and electrons in sample 2 were trapped much more than those in sample 1. Possible candidates of carrier capture centers are nitrogen and/or nitrogen-vacancy centers observed in PL, nonradiative defect (complex) centers, extended defects such as threading dislocations observed in micrographs taken with polarizers. The different growth conditions most likely affected crystallinity and responses to α-particles of the samples. [Copyright &y& Elsevier]

Abstract: Crystallinity of a freestanding large (size: ~9×7mm) undoped single crystal (SC) diamond film grown by plasma chemical vapor deposition (CVD) and radiation response of a sandwich-type radiation detector made from this SC plate to α particles were investigated. The freestanding SC film was formed by elimination of a substrate using a so-called “lift-off method” after the growth of a thick-film on a pre-ion-implanted substrate. The formed SC plate has a high optical transparency, indicating no remarkable optical absorption seen in the wavelength from ultraviolet to near-infrared region. In the energy spectra of 5.486MeV α-particles, relatively sharp peaks were observed for both hole and electron transits. For the hole transit, the peak resolution of the pulse height distribution and charge collection efficiency (CCE) were ~0.7% and 98%, respectively. On the other hand, for the electron transit, the peak resolution and CCE obtained were ~4.4% and 89%, respectively. In the photoluminescence spectrum at room temperature, a strong sharp peak around 235nm corresponding to free exciton and a weak visible band mainly related to nitrogen-vacancy complex were observed. The spectral width of the (004) plane X-ray rocking curve was 16.5″. The micrograph taken using crossed-polarizers demonstrated that there are some white regions and four-petaled patterns, originating from internal strain and most likely threading dislocations, respectively. [Copyright &y& Elsevier]

Abstract: In this article, we present a study of surface stress measurements of a thick single-crystal diamond (SCD) layer (110μm) deposited onto a high-temperature high-pressure (HTHP) Ib substrate. The measurement is based on observations of the deformation of the backside of the HTHP substrate due to internal stress that varies as the thickness of the SCD layer is modified by ion-beam etching. The deformation is obtained from the height-distribution analysis of interference microscopy (IM) observation. The results show that the tensile surface stress σ increases linearly with SCD-layer thickness with t f according to σ =0.065tf MPa/μm. The tensile surface stress may be attributed to the intrinsic stress that originates from the lattice mismatch between the CVD-diamond layer and the HTHP-Ib substrate. The increased internal stress is a principle cause of crack formation of the crystal. [ABSTRACT FROM AUTHOR]

Abstract: Crystallinity of freestanding large (size: ∼9×9mm) undoped single crystal (SC) diamond films grown by plasma chemical vapor deposition (CVD) was investigated using optical transmission spectroscopy, polarized optical microscope, X-ray rocking curves, X-ray topographs and photoluminescence. The production of the freestanding film was performed by elimination of the substrates using a so-called “lift-off method” after the growth of a homoepitaxial thick-film on a pre-ion-implanted substrate. The remarkable optical absorption in the wavelength from ultraviolet to near-infrared region (220–2500nm) was not seen, similarly to a high-pressure, high-temperature (HPHT) synthetic type-IIa diamond. The cross-nicol optical microscope image demonstrated that there are patchy white regions and many dotted patterns, originating from internal strain and threading dislocations, respectively, over the entire area of the sample. The dotted patterns, corresponding to threading dislocations observed in the cross-nicol image, were also observed in X-ray topographs. The full width at half maximum (FWHM) of the X-ray rocking curve was 19.8″. In photoluminescence spectra at room temperature, a strong sharp peak around 235nm corresponding to the recombination emission of free exciton was observed, while there were no remarkable emission peaks related to various defects typically observed in the visible region. [ABSTRACT FROM AUTHOR]

Abstract: Micro-Raman spectroscopy was used to evaluate the internal stress of the cross section of a large single crystal diamond (SCD) bulk of 9mm thickness, which was synthesized under a repetitive growth by using microwave plasma chemical vapor deposition (MWPCVD). The variation of internal stress estimated from Raman shift, is approximately 0.08GPa. In addition, the nitrogen effect on internal stress is evaluated approximately 4.05×10−2 GPa·ppm−1, which is based on our simplified model. [Copyright &y& Elsevier]

Dual-specificity phosphatases (DUSPs) catalyze the dephosphorylation of tyrosine and serine/threonine residues in target proteins. Atypical DUSPs (aDUSPs) lack substrate-binding motifs, suggesting their potential to target a diverse array of substrates. This study demonstrated that DUSP21, an aDUSP, is induced by leukemia inhibitory factor (LIF) in HeLa cells and acts as a negative regulator of LIF-induced signal transducer and activator of transcription 3 (STAT3) activation. Overexpressed DUSP21 co-localized and interacted with STAT3 in HeLa cells. Recombinant DUSP21 directly dephosphorylated STAT3 in vitro. Additionally, DUSP21 overexpression modulated STAT3-dependent growth of Ba/F3-G133 cells. These findings indicate that LIF-induced DUSP21 exerts an inhibitory effect on the LIF/STAT3 signaling pathway, thereby functioning as a suppressor of STAT3-mediated transcriptional activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia with a poor prognosis. In this study, we established a novel murine AEL model with Trp53 depletion and ERG overexpression. ERG overexpression in Trp53-deficient mouse bone marrow cells, but not in wild-type bone marrow cells, leads to AEL development within two months after transplantation with 100% penetrance. The established mouse AEL cells expressing Cas9 can be cultured in vitro, induce AEL in vivo even in unirradiated recipient mice, and enable efficient gene ablation using the CRISPR/Cas9 system. We also confirmed the cooperation between ERG overexpression and TP53 inactivation in promoting the growth of immature erythroid cells in human cord blood cells. Mechanistically, ERG antagonizes KLF1 and inhibits erythroid maturation, whereas TP53 deficiency promotes proliferation of erythroid progenitors. Furthermore, we identified HDAC7 as a specific susceptibility in AEL by the DepMap-based two-group comparison analysis. HDAC7 promotes the growth of human and mouse AEL cells both in vitro and in vivo through its non-enzymatic functions. Our study provides experimental evidence that TP53 deficiency and ERG overexpression are necessary and sufficient for the development of AEL and highlights HDAC7 as a promising therapeutic target for this disease., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: In treating acute hypoxemic respiratory failure (AHRF) caused by coronavirus disease 2019 (COVID-19), clinicians choose respiratory therapies such as low-flow nasal cannula oxygenation, high-flow nasal cannula oxygenation, or mechanical ventilation after assessment of the patient's condition. Chest computed tomography (CT) imaging contributes significantly to diagnosing COVID-19 pneumonia. However, the costs and potential harm to patients from radiation exposure need to be considered. This study was performed to predict the quantitative extent of COVID-19 acute lung injury using clinical indicators such as an oxygenation index and blood test results., Methods: We analyzed data from 192 patients with COVID-19 AHRF. Multiple logistic regression was used to determine correlations between the lung infiltration volume (LIV) and other pathophysiological or biochemical laboratory parameters., Results: Among 13 clinical parameters, we identified the oxygen saturation/fraction of inspired oxygen ratio (SF ratio) and serum lactate dehydrogenase (LD) concentration as factors associated with the LIV. In the binary classification of an LIV of ≥20 % or not and with the borderline LD = 2.2 × [SF ratio]-182.4, the accuracy, precision, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.828, 0.818, 23.400, and 0.870, respectively., Conclusions: These data suggest that acute lung injury due to COVID-19 pneumonia can be estimated using the SF ratio and LD concentration without a CT scan. These findings may provide significant clinical benefit by allowing clinicians to predict acute lung injury levels using simple, minimally invasive assessment of oxygenation capacity and biochemical blood tests., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Immunotherapy has attracted considerable attention as a therapeutic strategy for cancers including acute myeloid leukemia (AML). In this study, we found that the development of several aggressive subtypes of AML is slower in Rag2 -/- mice despite the lack of B and T lymphocytes, even compared to the immunologically normal C57BL/6 mice. Furthermore, an orally active p53-activating drug shows stronger antileukemia effect on AML in Rag2 -/- mice than C57BL/6 mice. Intriguingly, Natural Killer (NK) cells in Rag2 -/- mice are increased in number, highly express activation markers, and show increased cytotoxicity to leukemia cells in a coculture assay. B2m depletion that triggers missing-self recognition of NK cells impairs the growth of AML cells in vivo. In contrast, NK cell depletion accelerates AML progression in Rag2 -/- mice. Interestingly, immunogenicity of AML keeps changing during tumor evolution, showing a trend that the aggressive AMLs generate through serial transplantations are susceptible to NK cell-mediated tumor suppression in Rag2 -/- mice. Thus, we show the critical role of NK cells in suppressing the development of certain subtypes of AML using Rag2 -/- mice, which lack functional lymphocytes but have hyperactive NK cells., (© 2023. The Author(s).)

Objectives　At the beginning of the COVID-19 pandemic, the number of infected children was lower than that of adults. Most cases were transmitted in the family, asymptomatic, and severe cases were rare. In the sixth wave in Japan the number of infected children increased sharply after the Omicron variant had been replaced in December 2021, which had a substantial influence in maintaining social and medical functions. Furthermore, few reports on child death in the country have raised concerns among parents. However, no literature has elucidated the epidemiological characteristics of the Omicron variant in children. In this study, we aimed to clarify them during the sixth wave in Japan.Methods　We analyzed the data of 28,086 COVID-19-infected patients those were registered in the Yamashirokita Public Health Center between January 15, 2022 and May 31, 2022. The cumulative incidence and hospitalization rate were compared between the age groups <15 and those >15 years based on the databases compiled by our public health center and the Kyoto prefecture government. In addition, we analyzed the background, length of hospitalization, and clinical symptoms of 24 patients based on active epidemiological investigation, health observations, and discharge reports submitted from medical facilities.Results　Of the 52,897 residents <15 years (pediatric population is 12.3%), 15.1% (7,980 cases) were infected, and children accounted for 28.4% of all-age infected patients. Among them, 24 were hospitalized (0.3% of children with COVID-19, 0.04% of the child population). Conversely, of the 377,093 residents aged ≥15 years, 5.3% (20,106 patients) were infected. Among them, 1,088 were hospitalized (5.4% of COVID-19 patients, 0.28% of the adult population). For 24 hospitalized children, 22 (91.6%) had mild cases and 2 (8.3%) had moderate cases, and no severe case was noted based on the criteria of severity in Japan's COVID-19 medical care guidelines. Two patients (8.3%) were hospitalized for treatment of other diseases. The median of hospital stay was 3.5 days, and 20 patients (83.3%) were discharged home during the recuperation period.Conclusions　The cumulative incidence of children with COVID-19 in the sixth wave was 15.1%, approximately three times higher than that of the older patients; however, no severe case was observed in children.

Adjuvant therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer (EBC) remains challenging. The prognostic significance of HER2-low positivity in these patients is not fully understood. In our retrospective study, we analyzed 647 patients with HR-positive, HER2-negative, node-positive EBC, stratifying them into three cohorts based on axillary lymph node involvement, tumor size, and characteristics. Cohort 1 included patients with either ≥ 4 positive axillary lymph nodes or 1-3 positive nodes with histological grade 3 or tumor size ≥ 5 cm. Cohort 2 consisted of patients with 1-3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 ≥ 20%. Cohort 3 comprised patients with 1-3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 < 20%. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) between HER2-low (IHC1+ or IHC2+/FISH-) and HER2-zero (IHC0) groups in each cohort. In cohort 1, HER2-low patients exhibited significantly better 5-year IDFS (84.2% vs. 73.6%, p = 0.0213) and DRFS (88.2% vs. 79.8%, p = 0.0154). However, no significant differences were observed in cohorts 2 and 3. Our findings suggest HER2-low positivity as a prognostic factor in HR-positive, HER2-negative, and node-positive EBC., (© 2023. The Author(s).)

Background: Histological grade (HG) has been used in the MonrachE trial to select patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive high-risk early breast cancer (EBC). Although nuclear grade (NG) is widely used in Japan, it is still unclear whether replacing HG with NG can appropriately select high-risk patients., Methods: We retrospectively reviewed 647 patients with HR-positive, HER2-negative, node-positive EBC and classified them into the following four groups: group 1: ≥ 4 positive axillary lymph nodes (pALNs) or 1-3 pALNs and either grade 3 of both grading systems or tumors ≥ 5 cm; group 2: 1-3 pALNs, grade < 3, tumor < 5 cm, and Ki-67 ≥ 20%; group 3: 1-3 pALNs, grade < 3, tumor < 5 cm, and Ki-67 < 20%; and group 4: group 2 or 3 by HG classification but group 1 by NG classification. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) among the four groups using the Kaplan-Meier method with the log-rank test., Results: Group 1 had a significantly worse 5-year IDFS and DRFS than groups 2 and 3 (IDFS 80.8% vs. 89.5%, P = 0.0319, 80.8% vs. 95.5%, P = 0.002; DRFS 85.2% vs. 95.3%, P = 0.0025, 85.2% vs. 98.4%, P < 0.001, respectively). Group 4 also had a significantly worse 5-year IDFS (78.0%) and DRFS (83.6%) than groups 2 and 3., Conclusions: NG was useful for stratifying the risk of recurrence in patients with HR-positive, HER2-negative, node-positive EBC and was the appropriate risk assessment for patient groups not considered high-risk by HG classification., (© 2023. The Author(s).)

Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in de novo guanine nucleotide synthesis pathway. Although IMPDH inhibitors are widely used as effective immunosuppressants, their antitumor effects have not been proven in the clinical setting. Here, we found that acute myeloid leukemias (AMLs) with MLL-fusions are susceptible to IMPDH inhibitors in vitro. We also showed that alternate-day administration of IMPDH inhibitors suppressed the development of MLL-AF9-driven AML in vivo without having a devastating effect on immune function. Mechanistically, IMPDH inhibition induced overactivation of Toll-like receptor (TLR)-TRAF6-NF-κB signaling and upregulation of an adhesion molecule VCAM1, which contribute to the antileukemia effect of IMPDH inhibitors. Consequently, combined treatment with IMPDH inhibitors and the TLR1/2 agonist effectively inhibited the development of MLL-fusion AML. These findings provide a rational basis for clinical testing of IMPDH inhibitors against MLL-fusion AMLs and potentially other aggressive tumors with active TLR signaling., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Somatic mutations of ASXL1 are frequently detected in age-related clonal hematopoiesis (CH). However, how ASXL1 mutations drive CH remains elusive. Using knockin (KI) mice expressing a C-terminally truncated form of ASXL1-mutant (ASXL1-MT), we examined the influence of ASXL1-MT on physiological aging in hematopoietic stem cells (HSCs). HSCs expressing ASXL1-MT display competitive disadvantage after transplantation. Nevertheless, in genetic mosaic mouse model, they acquire clonal advantage during aging, recapitulating CH in humans. Mechanistically, ASXL1-MT cooperates with BAP1 to deubiquitinate and activate AKT. Overactive Akt/mTOR signaling induced by ASXL1-MT results in aberrant proliferation and dysfunction of HSCs associated with age-related accumulation of DNA damage. Treatment with an mTOR inhibitor rapamycin ameliorates aberrant expansion of the HSC compartment as well as dysregulated hematopoiesis in aged ASXL1-MT KI mice. Our findings suggest that ASXL1-MT provokes dysfunction of HSCs, whereas it confers clonal advantage on HSCs over time, leading to the development of CH.

Background: Hepatectomy is standard treatment for colorectal liver metastases; however, it is unclear whether liver metastases from other primary cancers should be resected or not. The Japanese Society of Hepato-Biliary-Pancreatic Surgery therefore created clinical practice guidelines for the management of metastatic liver tumors., Methods: Eight primary diseases were selected based on the number of hepatectomies performed for each malignancy per year. Clinical questions were structured in the population, intervention, comparison, and outcomes (PICO) format. Systematic reviews were performed, and the strength of recommendations and the level of quality of evidence for each clinical question were discussed and determined. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations., Results: The eight primary sites were grouped into five categories based on suggested indications for hepatectomy and consensus of the guidelines committee. Fourteen clinical questions were devised, covering five topics: (1) diagnosis, (2) operative treatment, (3) ablation therapy, (4) the eight primary diseases, and (5) systemic therapies. The grade of recommendation was strong for one clinical question and weak for the other 13 clinical questions. The quality of the evidence was moderate for two questions, low for 10, and very low for two. A flowchart was made to summarize the outcomes of the guidelines for the indications of hepatectomy and systemic therapy., Conclusions: These guidelines were developed to provide useful information based on evidence in the published literature for the clinical management of liver metastases, and they could be helpful for conducting future clinical trials to provide higher-quality evidence., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: On average, patients in Japan with type 2 diabetes mellitus have a clinical consultation every month, although evidence for a favorable follow-up interval is lacking. This study investigated whether the follow-up interval can be extended by comparing the clinical outcomes and cost for monthly versus bimonthly follow-up of patients with well-controlled diabetes mellitus., Methods: We combined administrative claims data from the National Health Insurance and the Health Checkups Program data of Tsu city, Japan between 2011 and 2014 to conduct a retrospective cohort study of patients with well-controlled type 2 diabetes mellitus. Propensity scores were used to assemble a matched-pairs cohort from patients who had monthly and bimonthly follow-up. Equivalence between two groups was assessed by designating the proportion of patients who maintained good control of their diabetes in the subsequent year as a primary outcome. The proportion achieving target blood pressure and lipid levels, favorable lifestyle, and annual cost were compared as secondary outcomes., Results: Of 12,145 participants, 693 with monthly follow-up and 693 with bimonthly follow-up were matched using propensity scores. In the monthly follow-up group 654 (94.4%) remained under good diabetic control, versus 658 (95.0%) in the bimonthly group (difference: 0.6%; 95% confidence interval: - 1.8 to 2.9%). All secondary outcomes were equivalent for the monthly and bimonthly follow-up groups except the proportion achieving target blood pressure, the proportion engaging in regular exercise, and annual cost., Conclusions: For patients with well-controlled diabetes mellitus, although frequent follow-up by a physician does not affect the control of blood glucose level in the subsequent year, the annual treatment cost becomes much higher. We suggest that patients with well-controlled diabetes can be followed up less often.

We report on the sensing stability of quantum nanosensors in aqueous buffer solutions for the two detection schemes of quantum decoherence spectroscopy and nanoscale thermometry. The electron spin properties of single nitrogen-vacancy (NV) centers in 25 nm-sized nanodiamonds have been characterized by observing individual nanodiamonds during a continuous pH change from 4 to 11. We have determined the stability of the NV quantum sensors during the pH change as the fluctuations of ±12% and ±0.2 MHz for the spin coherence time ( T 2 ) and the resonance frequency ( ω 0 ) of their mean values, which are comparable to the instrument error of the measurement system. We discuss the importance of characterizing the sensing stability during the pH change and how the present observation affects the measurement scheme of nanodiamond-based NV quantum sensing., Competing Interests: The authors declare no competing financial interests., (This journal is © The Royal Society of Chemistry.)

RUNX1 is a member of RUNX transcription factors and plays important roles in hematopoiesis. RUNX1 function is under the tight control through posttranslational modifications, including phosphorylation and ubiquitination. We previously developed a luminescence-based binding assay (AlphaScreen) to systematically detect RUNX1-interacting E3 ubiquitin ligases. In this study, we showed that a nuclear ubiquitin ligase RNF38 induced ubiquitination of RUNX1. RNF38-induced RUNX1 ubiquitination did not promote RUNX1 degradation, but rather stabilized RUNX1 protein. We also found that RNF38 enhanced RUNX1-mediated transcriptional repression of the erythroid master regulator KLF1 in K562 cells. Consequently, RNF38 cooperated with RUNX1 to inhibit erythroid differentiation of K562 cells. Thus, our study identified RNF38 as a novel E3 ligase that modifies RUNX1 function without inducing its degradation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Minimally invasive distal pancreatectomy (MIDP) has gained in popularity recently. However, there is no consensus on whether to preserve the spleen or not. In this study, we compared MIDP outcomes between spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS); as well as outcomes between splenic vessel preservation (SVP) and Warshaw's technique (WT)., Methods: A systematic search of PubMed (MEDLINE) and Cochrane Library was conducted and the reference lists of review articles were hand-searched., Results: Fifteen relevant studies with 769 patients were selected for meta-analyses of DPS and SPDP, while another 15 studies with 841 patients were used for the analysis between SVP and WT. Compared with the DPS group, SPDP patients had significantly lower incidences of infectious complications (P = 0.006) and pancreatic fistula (P = 0.002), shorter operative time (P < 0.001), and less blood loss (P = 0.01). Compared with WT, SVP patients had significantly lower incidences of splenic infarction (P < 0.001) and secondary splenectomy (P = 0.003). Subanalysis for laparoscopic surgery alone had similar results., Conclusions: Based on this study, SPDP has significantly superior outcomes compared to DPS. When a spleen is preserved, SVP has better outcomes over WT for reducing splenic complications., (© 2018 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Capturing the fast rotational motion of single nanoparticles has been hindered owing to the difficulty of acquiring directional information under the optical diffraction limit. Here, we report the linewidth broadening of the electron spin resonance of single nitrogen vacancy (NV) centers that matches the rotational diffusion constant of the host nanodiamonds. When nanodiamonds are gradually detached from the substrates that they were fixed to, their optically detected spin resonance peaks are broadened by 1.8 MHz, which corresponds to the rotational diffusion constant of nanoparticles with a diameter of 11.4 nm from the Einstein-Smoluchowski relation.

ASXL1 mutations occur frequently in myeloid neoplasms and are associated with poor prognosis. However, the mechanisms by which mutant ASXL1 induces leukaemogenesis remain unclear. In this study, we report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) and BAP1 in promoting myeloid leukaemogenesis. BAP1 expression results in increased monoubiquitination of ASXL1-MT, which in turn increases the catalytic function of BAP1. This hyperactive ASXL1-MT/BAP1 complex promotes aberrant myeloid differentiation of haematopoietic progenitor cells and accelerates RUNX1-ETO-driven leukaemogenesis. Mechanistically, this complex induces upregulation of posterior HOXA genes and IRF8 through removal of H2AK119 ubiquitination. Importantly, BAP1 depletion inhibits posterior HOXA gene expression and leukaemogenicity of ASXL1-MT-expressing myeloid leukemia cells. Furthermore, BAP1 is also required for the growth of MLL-fusion leukemia cells with posterior HOXA gene dysregulation. These data indicate that BAP1, which has long been considered a tumor suppressor, in fact plays tumor-promoting roles in myeloid neoplasms.