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Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated significant survival benefits for advanced non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, patients with EGFR-TKI treatment often develop acquired resistance subsequently. Transformation from NSCLC to small cell lung cancer (SCLC) is a rare EGFR-TKI resistance mechanism for patients with sensitive EGFR mutations. Herein, we report a NSCLC patient with EGFR exon 19 deletion treated with EGFR-TKI. During treatment, the pathological type of tumor showed transformation from NSCLC to combined SCLC and then to pure SCLC after acquiring EGFR-TKI resistance. Genomic analysis revealed that the EGFR exon 19 deletion, TP53 Y220H mutation, and retinoblastomal transcriptional corepressor 1 (RB1) F755V mutation existed persistently. Immunohistochemical results showed the loss of EGFR and RB1 expression in SCLC. The patient received multi-line chemotherapy with platinum agents and experienced a briefly effective window, but died of aggressive tumor progression. We profiled the transformation from NSCLC to SCLC of this case and pointed out the importance of repeat biopsy in response to EGFR-TKI resistance. Our results showed a novel RB1 F755V mutation which may be associated with RB1 loss. This report summarized the clinical characteristics, mechanisms, and predictors of SCLC transformation, and discussed the treatment after transformation.

In this work, we investigate the evolution of a Richtmyer-Meshkov (RM)-like instability occurring on the internal surface of particle rings impinged by divergent blast waves. Despite of the signature spike-bubble instability structure analogous to the hydrodynamic RM instability, the growth of the perturbation amplitude in granular media undergoes an exponential phase followed by a linear phase, markedly differing from the hydrodynamic RM instability, indicating a fundamentally different mechanism. The granular RM-like instability arises from the incipient transverse granular flows induced by the hydrodynamic effects upon the shock interaction. Whereas a substantial perturbation growth is initiated by the ensuing rarefaction dilation when the hydrodynamic effects are minimum. It is the interplay between the localized transverse and radial granular flows that sustains the persistent perturbation growth and drives the morphological changes of instability pattern alongside.

On the basis of the daily precipitation and mean temperature data of 583 meteorological stations, and AVHRR GIMMS NDVI materials from 1982 to 2006, the NDVI (annual maximum NDVI), annual precipitation and annual accumulated temperature above 10℃ (AT10) of grassland in vegetation regionalizations were obtained in China. Then the Mann-Kendall test and linear trend analysis were applied into the trend analysis of NDVI, precipitation and AT10 on per-pixel and vegetation regionalization scales respectively. And the correlation analysis and binary linear regression analysis were used to study the relation between NDVI and precipitation and AT10. The result showed that the NDVI of grassland was increasing significantly in the subtropical broadleaf evergreen forest regionalization, while the precipitation and AT10 were decreasing. And the NDVI of grassland are positive related to the precipitation and AT10 in temperate steppe and desert regionalization. The NDVI, precipitation and AT10 of grassland were increasing in Qinghai-Tibet plateau alpine vegetation regionalization. However, the NDVI-precipitation correlation and NDVI-AT10 correlation were negative and positive respectively.

Seedling establishment is inhibited on media containing high levels (∼6%) of glucose or fructose. Genetic loci that overcome the inhibition of seedling growth on high sugar have been identified using natural variation analysis and mutant selection, providing insight into sugar signaling pathways. In this study, a quantitative trait locus (QTL) analysis was performed for seedling sensitivity to high sugar in a Col/C24 F2 population of Arabidopsis thaliana. A glucose and fructose-sensing QTL, GSQ11, was mapped through selective genotyping and confirmed in near-isogenic lines in both Col and C24 backgrounds. Allelism tests and transgenic complementation showed that GSQ11 lies within the ANAC060 gene. The Col ANAC060 allele confers sugar insensitivity and was dominant over the sugar-sensitive C24 allele. Genomic and mRNA analyses showed that a single-nucleotide polymorphism (SNP) in Col ANAC060 affects the splicing patterns of ANAC060 such that 20 additional nucleotides are present in the mRNA. The insertion created a stop codon, resulting in a truncated ANAC60 protein lacking the transmembrane domain (TMD) that is present in the C24 ANAC060 protein. The absence of the TMD results in the nuclear localization of ANAC060. The short version of the ANAC060 protein is found in ∼12% of natural Arabidopsis accessions. Glucose induces GSQ11/ANAC060 expression in a process that requires abscisic acid (ABA) signaling. Chromatin immunoprecipitation-qPCR and transient expression analysis showed that ABI4 directly binds to the GSQ11/ANAC060 promoter to activate transcription. Interestingly, Col ANAC060 reduced ABA sensitivity and Glc-induced ABA accumulation, and ABI4 expression was also reduced in Col ANAC060 lines. Thus, the sugar-ABA signaling cascade induces ANAC060 expression, but the truncated Col ANAC060 protein attenuates ABA induction and ABA signaling. This negative feedback from nuclear ANAC060 on ABA signaling results in sugar insensitivity., Author Summary In plants, sugars function as signaling molecules that control important processes such as photosynthesis, growth, carbon distribution over different organs and the production of storage compounds. Sugar signaling requires the phytohormone abscisic acid (ABA) and the ABA-induced regulatory transcription factor ABI4. In this study, a genetic analysis identified the transcription factor ANAC060 as an important component in establishing sugar sensitivity. It was found that, in natural Arabidopsis thaliana populations, the ANAC060 protein may occur as a long or a short version due to differential ANAC060 mRNA splicing caused by a single-nucleotide polymorphism (SNP). The long ANAC060 protein with an intact transmembrane domain (TMD) is excluded from the nucleus, whereas the short version lacking the TMD is always present in the nucleus, where it regulates gene expression. Functional analyses indicated that Col ANAC060 is involved in a novel negative feedback loop in the sugar-ABA signaling pathway. In this feedback loop model, ABI4 activates ANAC060 expression, but the nuclear presence of Col ANAC060 suppresses Glc-induced ABA accumulation and ABI4 expression, thereby reducing responsiveness to sugar signals.