The lectin‐like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice

Ischemia and reperfusion injury (IRI) can occur in any tissue or organ. With respect to liver transplantation, the liver grafts from donors by definition experience transient ischemia and subsequent blood reflow. IRI is a problem not only in organ transplantation but also in cases of thrombosis or circulatory disorders such as mesenteric ischemia, myocardial, or cerebral infarction. We have reported that recombinant human soluble thrombomodulin (rTM), which is currently used in Japan to treat disseminated intravascular coagulation (DIC), has a protective effect and suppresses liver IRI in mice. However, rTM may not be fully safe to use in humans because of its inherent anticoagulant activity. In the present study, we used a mouse liver IRI model to explore the possibility that the isolated lectin-like domain of rTM (rTMD1), which has no anticoagulant activity, could be effective as a therapeutic modality for IRI. Our results indicated that rTMD1 could suppress ischemia and reperfusion-induced liver damage in a dose-dependent manner without concern of associated hemorrhage. Surprisingly, rTMD1 suppressed the liver damage even after IR insult had occurred. Taken together, we conclude that rTMD1 may be a candidate drug for prevention of and therapy for human liver IRI without the possible risk of hemorrhage

分子イオン注入技術によりゲッタリング能力を付与した高感度CMOSイメージセンサ向けSiウェーハ

2023年

Proximity Gettering Design of Hydrocarbon–Molecular–Ion–Implanted Silicon Wafers Using Dark Current Spectroscopy for CMOS Image Sensors

We developed silicon epitaxial wafers with high gettering capability by using hydrocarbon−molecular−ion implantation. These wafers also have the effect of hydrogen passivation on process-induced defects and a barrier to out-diffusion of oxygen of the Czochralski silicon (CZ) substrate bulk during Complementary metal-oxide-semiconductor (CMOS) device fabrication processes. We evaluated the electrical device performance of CMOS image sensor fabricated on this type of wafer by using dark current spectroscopy. We found fewer white spot defects compared with those of intrinsic gettering (IG) silicon wafers. We believe that these hydrocarbon−molecular−ion−implanted silicon epitaxial wafers will improve the device performance of CMOS image sensors

Reduction of White Spot Defects in CMOS Image Sensors Fabricated Using Epitaxial Silicon Wafer with Proximity Gettering Sinks by CH₂P Molecular Ion Implantation

Using a new implantation technique with multielement molecular ions consisting of carbon, hydrogen, and phosphorus, namely, CH2P molecular ions, we developed an epitaxial silicon wafer with proximity gettering sinks under the epitaxial silicon layer to improve the gettering capability for metallic impurities. A complementary metal-oxide-semiconductor (CMOS) image sensor fabricated with this novel epitaxial silicon wafer has a markedly reduced number of white spot defects, as determined by dark current spectroscopy (DCS). In addition, the amount of nickel impurities gettered in the CH2P-molecular-ion-implanted region of this CMOS image sensor is higher than that gettered in the C3H5-molecular-ion-implanted region; and this implanted region is formed by high-density black pointed defects and deactivated phosphorus after epitaxial growth. From the obtained results, the CH2P-molecular-ion-implanted region has two types of complexes acting as gettering sinks. One includes carbon-related complexes such as aggregated C–I, and the other includes phosphorus-related complexes such as P4–V. These complexes have a high binding energy to metallic impurities. Therefore, CH2P-molecular-ion-implanted epitaxial silicon wafers have a high gettering capability for metallic impurities and contribute to improving the device performance of CMOS image sensors. (This manuscript is an extension from a paper presented at the 6th IEEE Electron Devices Technology & Manufacturing Conference (EDTM 2022))

TEM Image Analysis and Simulation Physics for Two-Step Recrystallization of Discretely Amorphized C₃H₅-Molecular-Ion-Implanted Silicon Substrate Surface

In this study, we investigate the initial rapid recrystallization of a discretely amorphized C3H5-molecular-ion-implanted silicon (Si) substrate surface in the subsequent thermal annealing treatment through the analysis of plan-view transmission electron microscopy (TEM) images and technology computer-aided design (TCAD) process simulation. In the approach of the analysis of the plan-view TEM image of the Si substrate surface, we found that initial rapid recrystallization occurs in the intermediate regions between the residual crystalline and discrete amorphous regions formed in the C3H5-molecular-ion-implanted Si substrate surface. In addition, the TCAD process simulation results indicate that the intermediate regions correspond to the amorphous pockets formed around the discrete amorphous regions in the C3H5-molecular-ion-implanted Si substrate surface and are recrystallized preferentially during the short thermal annealing time. These plan-view TEM image analysis and TCAD process simulation results reveal a two-step recrystallization of the discretely amorphized C3H5-molecular-ion-implaned Si substrate surface. After the initial rapid recrystallization of amorphous pockets in the 1st step, the recrystallization of discrete amorphous regions starts in the 2nd step. The incubation period between the 1st and 2nd steps is the time required to recrystallize the amorphous pockets around the discrete amorphous regions completely and redefine the amorphous/crystalline interface

Highlighting Interleukin-36 Signalling in Plaque Psoriasis and Pustular Psoriasis

Plaque psoriasis and pustular psoriasis are overlapping, but distinct, disorders. The therapeutic response to biologics supports the pivotal role of the tumour necrosis alpha (TNF-?)/ interleukin (IL)-23/IL-17/IL-22 axis in the pathogenesis of these disorders. Recently, functional activation of the IL-36 receptor (IL-36R) was discovered to be another driving force in the pathogenesis of psoriasis. This was first highlighted by the discovery that a loss-of-function mutation of the IL-36R antagonist (IL-36Ra) causes pustular psoriasis. Although the TNF-?/IL-23/IL-17/IL-22 axis and the functional activation of IL-36R are fundamentally involved in plaque psoriasis and pustular psoriasis, respectively, the 2 pathways are closely related and mutually reinforced, resulting in full-blown clinical manifestations. This review summarizes current topics on how IL-36 agonists (IL-36?, IL-36?, IL-36?) signal IL-36R, the pathological expression of IL-36 agonists and IL-36Ra in plaque and pustular psoriatic lesions, and the cross-talk between the TNF-?/IL-23/IL-17/IL-22 axis and the functional activation of IL-36R in the epidermal milieu

Effect of an Introduced Phytoene Synthase Gene Expression on Carotenoid Biosynthesis in the Marine Diatom Phaeodactylum tricornutum

Carotenoids exert beneficial effects on human health through their excellent antioxidant activity. To increase carotenoid productivity in the marine Pennales Phaeodactylum tricornutum, we genetically engineered the phytoene synthase gene (psy) to improve expression because RNA-sequencing analysis has suggested that the expression level of psy is lower than other enzyme-encoding genes that are involved in the carotenoid biosynthetic pathway. We isolated psy from P. tricornutum, and this gene was fused with the enhanced green fluorescent protein gene to detect psy expression. After transformation using the microparticle bombardment technique, we obtained several P. tricornutum transformants and confirmed psy expression in their plastids. We investigated the amounts of PSY mRNA and carotenoids, such as fucoxanthin and β-carotene, at different growth phases. The introduction of psy increased the fucoxanthin content of a transformants by approximately 1.45-fold relative to the levels in the wild-type diatom. However, some transformants failed to show a significant increase in the carotenoid content relative to that of the wild-type diatom. We also found that the amount of PSY mRNA at log phase might contribute to the increase in carotenoids in the transformants at stationary phase