Kleinwestergaard2047

Immunotherapy has become a hotspot in cancer therapy in recent years. Several immune checkpoints inhibitors have been used to treat lung cancer. CD137 is a kind of costimulatory molecule that mediates T cell activation, which regulates the activity of immune cells in a variety of physiological and pathological processes. Targeting CD137 or its ligand (CD137L) has been studied aiming to enhance anti-cancer immune responses. Accumulating studies present that anti-CD137 monoclonal antibodies alone or combined with other drugs have bright antitumor prospect. In the following, we reviewed the biology of CD137, the anti-tumor effects of anti-CD137 antibody monotherapy and the combined therapy in lung cancer. © 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.Studies on N2 activation and transformation by transition metal hydride complexes are of particular interest and importance. The synthesis and diverse transformations of a dinitrogen dititanium hydride complex bearing the rigid acridane-based acri PNP-pincer ligands [(acri PNP)Ti]2 (μ2 -η1 η2 -N2 )(μ2 -H)2 are presented. This complex enabled N2 cleavage and hydrogenation even without additional H2 or other reducing agents. Furthermore, diverse transformations of the N2 unit with a variety of organometallic compounds such as ZnMe2 , MgMe2 , AlMe3 , B(C6 F5 )3 , PinBH, and PhSiH3 have been well established at the rigid acri PNP-ligated dititanium framework, such as reversible bonding-mode change between the end-on and side-on/end-on fashions, diborylative N=N bond cleavage, the formal insertion of two dimethylaluminum species into the N=N bond, and the formal insertion of two silylene units into the N=N bond. This work has revealed many unprecedented aspects of dinitrogen reaction chemistry. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Astrocytes are involved in several aspects of neuronal development and properties which are altered in intellectual disability (ID). Oligophrenin-1 is a RhoGAP protein implicated in actin cytoskeleton regulation, and whose mutations are associated with X-linked ID. Oligophrenin-1 is expressed in neurons, where its functions have been widely reported at the synapse, as well as in glial cells. However, its roles in astrocytes are still largely unexplored. Using in vitro and in vivo models of oligophrenin1 disruption in astrocytes, we found that oligophrenin1 regulates at the molecular level the RhoA/ROCK/MLC2 pathway in astroglial cells. We also showed at the cellular level that oligophrenin1 modulates astrocyte morphology and migration both in vitro and in vivo, and is involved in glial scar formation. Altogether, these data suggest that oligophrenin1 deficiency alters not only neuronal but also astrocytic functions, which might contribute to the development of ID. © 2020 Wiley Periodicals, Inc.Plants produce numerous metabolites that are important for their development and growth. However, the genetic architecture of the wheat metabolome has not been well studied. Here, utilizing a high-density genetic map, we conducted a comprehensive metabolome study via widely targeted LC-MS/MS to analyse the wheat kernel metabolism. We further combined agronomic traits and dissected the genetic relationship between metabolites and agronomic traits. In total, 1260 metabolic features were detected. Using linkage analysis, 1005 metabolic quantitative trait loci (mQTLs) were found distributed unevenly across the genome. Twenty-four candidate genes were found to modulate the levels of different metabolites, of which two were functionally annotated by in vitro analysis to be involved in the synthesis and modification of flavonoids. Combining the correlation analysis of metabolite-agronomic traits with the co-localization of mQTL and phenotypic QTL (pQTL), genetic relationships between the metabolites and agronomic traits were uncovered. For example, a candidate was identified using correlation and co-localization analysis that may manage auxin accumulation, thereby affecting number of grains per spike (NGPS). Furthermore, metabolomic data were used to predict the performance of wheat agronomic traits, with metabolites being found that provide strong predictive power for NGPS and plant height. This study used metabolomic and association analysis to better understand the genetic basis of the wheat metabolism which will ultimately assist in wheat breeding. This article is protected by copyright. All rights reserved.AIM Bile salt export pump (BSEP) deficiency manifests a form of progressive intrahepatic cholestasis. This study aimed to establish a scoring system of liver histology for the uncommon genetic condition. METHODS After a roundtable discussion and a histology review, a scoring system for BSEP deficiency was established. Eleven tissue samples were independently evaluated by three pathologists based on the proposed standard for an interobserver agreement analysis. In four cases with serial tissue samples available, correlation between changes in histology scores and clinical outcome was examined. check details RESULTS Of 14 initially listed histopathological findings, 12 were selected for scoring and grouped into the following four categories cholestasis, parenchymal changes, portal tract changes, and fibrosis. Each category consisted of two to four microscopic findings that were further divided into three to six scores; therefore, each category had a maximum score of 8 to 11. Interobserver agreement was highest for pericellular fibrosis (κ value 0.849) and lowest for hepatocellular cholestasis (κ value 0.241) with the mean and median κ values of the 12 parameters being 0.561 and 0.602, respectively. For two patients whose clinical features worsened, score changes between two time points were interpreted as deteriorated. In two patients, who showed a good clinical response to preprandial treatment with sodium 4-phenylbutyrate, histological changes were evaluated as improved or unchanged. CONCLUSIONS The proposed histology-based scoring system for BSEP deficiency with moderate interobserver agreement may be useful not only for monitoring microscopic changes in the clinical practice but also for a surrogate endpoint in clinical trials. This article is protected by copyright. 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