[3H]9-Methyl-7-bromoeudistomin D, a caffeine-like powerful Ca2+ releaser, binds to caffeine-binding sites distinct from the ryanodine receptors in brain microsomes

Abstract[3H]9-Methyl-7-bromoeudistomin D ([3H]MBED), the most powerful Ca2+ releaser from sarcoplasmic reticulum, specifically bound to the brain microsomes. Caffeine competitively inhibited [3H]MBED binding. [3H]MBED binding was markedly blocked by procaine, whereas that was enhanced by adenosine-5′-(β,γ-methylene)triphosphate. The Bmax value was 170 times more than that of [3H]ryanodine binding. The profile of sucrose-density gradient centrifugation of solubilized microsomes indicated that [3H]MBED binding protein was different from [3H]ryanodine binding protein. These results suggest that there are MBED/caffeine-binding sites in brain that are distinct from the ryanodine receptor and that MBED becomes an essential molecular probe for characterizing caffeine-binding protein in the central nervous system

Upregulation of Histidine Decarboxylase Immunoreactivity in Neointimal Smooth Muscle Cells of Balloon-injured Porcine Coronary Arteries

粥状動脈硬化により狭窄した冠動脈にバルーンを挿入して拡張する経皮的冠動脈形成術(PTCA)はステントと併用して広く行われているが、術後の再狭窄が問題となっている。再狭窄の主な原因は、血管中膜平滑筋細胞の内膜への遊走と増殖による内膜肥厚である。この過程には、血小板由来増殖因子など種々のペプチド性増殖因子の関与が示唆されているが、非ペプチド性因子の関与については明らかでない。我々は、ブタ冠動脈バルーン障害モデルの内膜肥厚部位に、著しいヒスタミン含量の増加を見出し報告して来た。一般に、組織中のヒスタミンは、肥満細胞中に貯蔵され遊離されるか、ヒスチジン脱炭酸酵素(HDC)により新規に合成分泌される。そこで、本研究では、ブタ冠動脈バルーン障害モデルにおけるHDCの分布を免疫組織化学的に検討し、内膜肥厚部位に著しいHDCの発現を明らかにした。また、ウェスタンブロット解析の結果、内膜肥厚部位を含む血管に63kDaのHDC陽性バンドを検出した。このことからヒスタミンは、内膜肥厚部位の平滑筋細胞から合成分泌されていることが示唆された。(著者抄録

Interface regulation of micro-sized sintered Ag-10Al composite based on in-situ surface modification and enhanced microstructure stability in power electronic packaging

The increasing demand for high-power SiC semiconductors necessitate the development of a die attachment material that combines high-temperature resistance, reliability, and cost-effectiveness. In this study, a novel micro-sized composite, Ag-10Al paste, containing 10 wt% Al particles, was designed. A remarkable phenomenon, the ejection of ultrafine Ag nanoparticles from micron-sized Ag flakes, was observed for the first time. The phenomenon was utilized for the in-situ surface modification of Al. Subsequently, the microstructure and mechanical properties of the sintered Ag-10Al/direct bonded copper (DBC) joints were studied. Results indicated that the Ag-10Al composite exhibited superior microstructure stability compared to sintered Ag. The Ag/Al interface was systematically analyzed, revealing a unique Ag/nano Ag2O/Al2O3 amorphous/Al structure. This structure was formed through the Ag nanoparticle jetting effect of Ag flakes, achieving effective bonding between nano Ag2O and Al2O3 amorphous phases through mutual dissolution at the atomic level. Moreover, the sintered Ag-10Al joint demonstrated enhanced mechanical performance stability over the sintered Ag joint. After 1000 h aging at 300 ℃, the shear strength of the sintered Ag-10Al joint reached 34.1 MPa, meeting the requirements for power semiconductor packaging. In conclusion, the Ag-10Al composite paste was thoughtfully designed, excelling in both performance and cost-effectiveness

Design of Ni-rGO reinforced Sn2.5Ag0.7Cu0.1Ce composite solder based on micro-alloying and composite principles: Microstructure and properties

Based on the principles of micro-alloying and composite, the graphene reinforced Sn2.5Ag0.7Cu0.1Ce composite solder was designed. Ni nanoparticle-modified reduced graphene oxide (Ni-rGO) was prepared by thermal decomposition method, and the powder-melting method was proposed for the first time to prepare Ni-rGO reinforced Sn2.5Ag0.7Cu0.1Ce composite solder. The microstructure, wettability, electrical resistivity, and mechanical properties of the composite solder were systematically studied. Results indicated that the Ni nanoparticles uniformly adhered to the rGO with a size of 26.3 nm. The effective incorporation of Ni-rGO into the solder matrix was achieved. The result broke the technical difficulty that graphene cannot be effectively added to low melting point metals. With the addition of Ni-rGO, the grain size gradually decreased, and the eutectic structures increased. Deep etching results revealed that columnar β-Sn was stacked from layered β-Sn, the addition of 0.05 wt% Ni-rGO led to an increase in sheet-like Ag3Sn within the eutectics. Additionally, Ni-rGO was found at the grain boundaries of composite solder, serving as nucleation sites for Ag3Sn and Cu6Sn5. At an addition of 0.05 wt%, the tensile strength reaches a maximum of 58.1 MPa, with elongation of 33.8%, surpassing the strength of commercial Sn3.0Ag0.5Cu solder. Therefore, the high-strength and tough composite solder was obtained. This study offered a new approach for the development of low-melting-point composite materials

Hyper-reactivity of diacylglycerol kinase is involved in the dysfunction of aortic smooth muscle contractility in streptozotocin-induced diabetic rats

1. Dysfunction of vascular contraction in diabetes has been reported; however, the mechanisms are poorly understood. In this study, calcium sensitization involving increases in contraction in streptozotocin-induced diabetic rat aorta was detected. We hypothesize that an alteration in the intracellular signalling system plays a role in the dysfunction of vascular contractility in diabetes. Therefore, diacylglycerol (DG) kinase as a key enzyme of phosphatidylinositol (PI) turnover was investigated. 2. Treatment with norepinephrine (NE) caused time- and dose-dependent activation of DG kinase in control rats. This activation required simultaneous increases in intracellular calcium concentration ([Ca(2+)](i)) and protein kinase C (PKC) activation. 3. In diabetic rats, hyper-reactivity of DG kinase involving inactivation in the resting state and over-activation in NE stimulation was observed. During hyper-reactivity, [Ca(2+)](i) dependency of DG kinase was enhanced. Treatment with 50 mM KCl induced significant escalation in activity; moreover, basal activation of PKC was detected only in diabetes. These results suggested that PKC had been activated in the resting state. In contrast, these conditions were insufficient for DG kinase activation due to the absence of [Ca(2+)](i) elevation. 4. During NE-stimulation, PKC activation was maintained and [Ca(2+)](i) increased. Therefore, DG kinase was activated and an elevation in calcium dependency enhanced this activation. 5. The present study suggested that DG kinase hyper-reactivity in diabetes involved both an increase in [Ca(2+)](i) and basal activation of PKC. This phenomenon may be associated with increased vascular contraction in diabetes mediated by acceleration of PI-turnover

Distribution and clinical impact of molecular subtypes with dark zone signature of DLBCL in a Japanese real-world study

The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone (DZ) that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, which include the DZ signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a data set from the cohort of British Columbia Cancer (BCC) (n = 804). Through the 1050 patient samples on which DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to have germinal center B-cell–like (GCB) DLBCL, activated B-cell–like (ABC) DLBCL, and DZsig-positive (DZsigpos) DLBCL, respectively, with the highest prevalence of ABC-DLBCL, differing significantly from the BCC result (P < .001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with 2-year overall survival rates of 88%, 75%, and 66%, respectively (P < .0001), with patients with DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes after rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all, P < .05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas