The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large‐cell lymphoma. Since then, ALK has been associated with other types of cancers, including non‐small‐cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK‐rearrangement (ALK‐R), and the ALK‐tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.

Fatty acids (FAs) and FA-derived complex lipids play important roles in plant growth and vegetative development and are a class of prominent metabolites stored in mature seeds. The factors and regulatory networks that control FA accumulation in plant seeds remain largely unknown. The role of TRANSPARENT TESTA8 (TT8) in the regulation of flavonoid biosynthesis and the formation of seed coat color is extensively studied; however, its function in affecting seed FA biosynthesis is poorly understood. In this article, we show that Arabidopsis (Arabidopsis thaliana) TT8 acts maternally to affect seed FA biosynthesis and inhibits seed FA accumulation by down-regulating a group of genes either critical to embryonic development or important in the FA biosynthesis pathway. Moreover, the tt8 mutation resulted in reduced deposition of protein in seeds during maturation. Posttranslational activation of a TT8-GLUCOCORTICOID RECEPTOR fusion protein and chromatin immunoprecipitation assays demonstrated that TT8 represses the activities of LEAFY COTYLEDON1, LEAFY COTYLEDON2, and FUSCA3, the critical transcriptional factors important for seed development, as well as CYTIDINEDIPHOSPHATE DIACYLGLYCEROL SYNTHASE2, which mediates glycerolipid biosynthesis. These results help us to understand the entire function of TT8 and increase our knowledge of the complicated networks regulating the formation of FA-derived complex lipids in plant seeds.

These authors contributed equally to this work. SUMMARYTRANSPARENT TESTA2 (TT2) regulates the biosynthesis of proanthocyanidins in the seed coat of Arabidopsis. We recently found that TT2 also participates in inhibition of fatty acid (FA) biosynthesis in the seed embryo. However, the mechanism by which TT2 suppresses the accumulation of seed FA remains unclear. In this study, we show that TT2 is expressed in embryos at an early developmental stage. TT2 is directly bound to the regulatory region of FUSCA3 (FUS3), and mediates the expression of numerous genes in the FA biosynthesis pathway. These genes include BCCP2, CAC2, MOD1 and KASII, which encode proteins involved in the initial steps of FA chain formation, FAD2 and FAD3, which are responsible for FA desaturation, and FAE1, which catalyzes very-long-chain FA elongation. Loss of function of TT2 results in reduced expression of GLAB-RA2 but does not cause a significant reduction in the mucilage attached to the seed coats, which competes with FA for photosynthates. TT2 is expressed in both maternal seed coats and embryonic tissues, but proanthocyanidins are only found in wild-type seed coats and not in embryonic tissues. The amount of proanthocyanidins in the seed coat is negatively correlated with the amount of FAs in the embryo.

Previous studies based on microarray analysis have found that DELLAs down-regulate several GDSL genes in unopened flowers and/or imbibed seeds. This suggests the role of DELLAs in seed fatty acid (FA) metabolism. In the present study, enhancement of gibberellin (GA) signalling through DELLA mutation or exogenous gibberellin acid A3 (GA3) resulted in the up-regulated expression of transcription factors for embryogenesis and seed development, genes involved in the FA biosynthesis pathway, and five GDSL-type Seed Fatty Acid Reducer (SFAR) genes. SFAR overexpression reduced the total seed FA content and led to a particular pattern of seed FA composition. This 'SFAR footprint' can also be found in plants with enhanced GA3 signalling. By contrast, the loss of SFAR function dramatically increases the seed FA content. The transgenic lines that overexpress SFAR were less sensitive to stressful environments, reflected by a higher germination rate and better seedling establishment compared with the wild type (WT) plants. The GDSL-type hydrolyzer is a family of proteins largely uncharacterized in Arabidopsis. Their biological function remains poorly understood. SFAR reduces seed FA storage and acts downstream of the GA signalling pathway. We provide the first evidence that some GDSL proteins are somehow involved in FA degradation in Arabidopsis seeds.

BackgroundHeart failure (HF) is an emerging epidemic in China and accounts for significant healthcare resource utilization in the inpatient setting. To create evidence‐based, life‐saving, and cost‐saving hospitalization systems, the first step is to characterize the contemporary national landscape of inpatient HF care.Methods and ResultsIn the China PEACE 5r‐HF study (China Patient‐centered evaluative Assessment of Cardiac Events Retrospective Study of Heart Failure), we used 2‐stage random sampling to create a nationally representative cohort of 10 004 admissions for HF from 189 hospitals in 2015 in China. Data on patient characteristics, management, and outcomes were obtained through centralized medical record abstraction. The median age of the cohort was 73 years (interquartile range, 65–80), and 48.9% were women. More than half (56.2%) of the patients were hospitalized in rural areas. Prevalence of ejection fraction ≥50%, 40% to 50%, and <40% was 60.3%, 17.7%, and 22.0%, respectively. We identified substantial gaps in care, including underutilization of diagnostic tests such as echocardiograms (63.6%), chest imaging (75.2%), and biomarker testing (56.4%), low prescription rates of guideline‐recommended medications during hospitalization and at discharge, suboptimal rates of follow‐up appointments (24.3%), and widespread utilization of traditional Chinese medicine (74.8%). The combined rate of in‐hospital mortality and treatment withdrawal in our study was 3.5%, and median length‐of‐stay was 9 days (interquartile range, 7–13).ConclusionsPatients admitted with acute HF in China have distinctive epidemiology and receive substandard care, but have low inpatient mortality despite long length of stay. These findings provide opportunities for streamlining efficiencies while improving quality of inpatient HF care in China.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT02877914.