Programmed cell death 4 (PDCD4) is a newly described tumour suppressor that inhibits oncogenesis by suppressing gene transcription and translation. Loss of PDCD4 expression has been found in several types of human cancers including the most common cancer of the brain, the gliomas. However, the molecular mechanisms responsible for PDCD4 gene silencing in tumour cells remain unclear. Here we report the identification of 5′CpG island methylation as the predominant cause of PDCD4 mRNA silencing in gliomas. The methylation of the PDCD4 5′CpG island was found in 47% (14/30) of glioma tissues, which was significantly associated with the loss of PDCD4 mRNA expression (γ=−1.000, P < 0.0001). Blocking methylation in glioma cells using a DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine, restored the PDCD4 gene expression, inhibited their proliferation and reduced their colony formation capacity. Longitudinal studies of a cohort of 84 patients with gliomas revealed that poor prognosis of patients with high-grade tumours were significantly associated with loss of PDCD4 expression. Thus, our current study suggests, for the first time, that PDCD4 5′CpG island methylation blocks PDCD4 expression at mRNA levels in gliomas. These results also indicate that PDCD4 reactivation might be an effective new strategy for the treatment of gliomas.

Land surface temperature (LST) is a crucial parameter that reflects land-atmosphere interaction and has thus attracted wide interest from geoscientists. Owing to the rapid development of Earth observation technologies, remotely sensed LST is playing an increasingly essential role in various fields. This review aims to summarize the progress in LST estimation algorithms and accelerate its further applications. Thus, we briefly review the most-used thermal infrared (TIR) LST estimation algorithms. More importantly, this review provides a comprehensive collection of the widely used TIR-based LST products and offers important insights into the uncertainties in these products with respect to different land cover conditions via a systematic intercomparison analysis of several representative products. In addition to the discussion on product accuracy, we address problems related to the spatial discontinuity, spatiotemporal incomparability, and short time span of current LST products by introducing the most effective methods. With the aim of overcoming these challenges in available LST products, much progress has been made in developing spatiotemporal seamless LST data, which significantly promotes the successful applications of these products in the field of surface evapotranspiration and soil moisture estimation, agriculture drought monitoring, thermal environment monitoring, thermal anomaly monitoring, and climate change. Overall, this review encompasses the most recent advances in TIR-based LST and the state-of-the-art of applications of LST products at various spatial and temporal scales, identifies critical further research needs and directions to advance and optimize retrieval methods, and promotes the application of LST to improve the understanding of surface thermal dynamics and exchanges.Plain Language Summary Land surface temperature (LST) is a crucial geophysical parameter related to surface energy and water balance of the land-atmosphere system. Satellite remote sensing provides the best way to measure LST and generate various LST products at regional and global scales. In this review, to facilitate the application of LST products in different fields, we first present the physical meaning of satellite-derived LST. Subsequently, we summarize recent advances in LST retrieval and validation methods, with a special focus on the state-of-the-art product collections, product accuracies and intercomparisons, and main problems in current LST products as well as their possible solutions. Additionally, we also review the major applications of LST products in agricultural drought monitoring, thermal environment monitoring, thermal anomaly monitoring, and climate change. Finally, we offer recommendations or perspectives to promote LST retrieval methods and their applications. This review will aid the user in gaining a thorough comprehensive understanding of satellite-derived LST products and promoting their appropriate applications. LI ET AL.

Disorders of sexual development (DSD) are estimated to occur in 1 of 4500 births. Since the genetic etiology of DSD is highly heterogeneous, obtaining a definitive molecular diagnosis by single gene test is challenging. Utilizing a high-throughput sequencing upfront is proposed as an efficient approach to aid in the diagnosis. This study aimed to examine the diagnostic yield of next-generation sequencing in DSD. 32 DSD patients that previously received clinical examinations and single gene tests were selected, with or without a diagnosis. Prior single gene tests were masked, and then samples went through targeted next-generation sequencing of 80 genes from which the diagnostic yield was assessed. A likely diagnosis, with pathogenic or likely pathogenic variants identified, was obtained from nine of the 32 patients (i.e., 28.1%, versus 10% by single gene tests). In another five patients (15.6%), variants of uncertain significance were found. Among 18 variants identified (i.e., 17 single nucleotide variants and one small deletion), eight had not been previously reported. This study supports the notion that next-generation sequencing can be an efficient tool in the clinical diagnosis and variant discovery in DSD.

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