Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1–E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.
Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we investigate the composition of ESCC tumors based on 208,659 single-cell transcriptomes derived from 60 individuals. We identify 8 common expression programs from malignant epithelial cells and discover 42 cell types, including 26 immune cell and 16 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and analyse the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we link the cancer cell transcriptomes to the somatic mutations and identify several markers significantly associated with patients’ survival, which may be relevant to precision care of ESCC patients. These results reveal the immunosuppressive status in the ESCC TME and further our understanding of ESCC.
Naturally colored cotton (Gossypium hirsutum L.) fibers (CCFs) are of interest in the textile industry because they require little dyeing and result in less environmental pollution. Pigmentation is one of the most important factors that differentiate CCFs from white cotton fiber (WCF) during fiber maturation. Many factors are involved in pigmentation, some of which we compared between CCFs and WCF with isogenetic backgrounds. These included the type of pigment, the activity of phenylalanine ammonia lyase (PAL), the concentration of total carbohydrates, and the type of soluble saccharide. We aimed to determine the causes of different fiber colors and found that flavonoids were the dominant type of pigment in the CCFs. At maturity (50 d post anthesis [DPA]), the WCF had only about 1/3 the amount of flavonoids as the brown cotton fiber (BCF) and 1/10 that of the green cotton fiber (GCF). During the course of fiber maturation (in particular, the stage before 8 DPA), CCFs had much higher PAL activity than the WCF. Of the fibers, the GCF had the highest concentration of carbohydrates over the course of maturation. However, higher concentrations of total carbohydrates did not always lead to higher concentrations of cellulose. This was very likely due to the synthesis of flavonoids and their derivatives consuming a large amount of carbohydrates that otherwise might be used for the synthesis of cellulose.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, we know little of mutational spectrum in the Chinese population. Thus, here we report the identification of somatic mutations for Chinese PTC using 402 tumor-normal pairs (Discovery: 91 pairs via exome sequencing; validation: 311 pairs via Sanger sequencing). We observed three distinct mutational signatures, evidently different from the two mutational signatures among Caucasian PTCs. Ten significantly mutated genes were identified, most previously uncharacterized. Notably, we found that long non-coding RNA (lncRNA) GAS8-AS1 is the secondary most frequently altered gene and acts as a novel tumor suppressor in PTC. As a mutation hotspot, the c.713A>G/714T>C dinucleotide substitution was found among 89.1% patients with GAS8-AS1 mutations and associated with advanced PTC disease (P = 0.009). Interestingly, the wild-type lncRNA GAS8-AS1 (A713T714) showed consistently higher capability to inhibit cancer cell growth compared to the mutated lncRNA (G713C714). Further studies also elucidated the oncogene nature of the G protein-coupled receptor LPAR4 and its c.872T>G (p.Ile291Ser) mutation in PTC malignant transformation. The BRAF c.1799T>A (p.Val600Glu) substitution was present in 59.0% Chinese PTCs, more frequently observed in patients with lymph node metastasis (P = 1.6 × 10(-4)). Together our study defines a exome mutational spectrum of PTC in the Chinese population and highlights lncRNA GAS8-AS1 and LPAR4 as potential diagnostics and therapeutic targets.
Background: Inhibitory control is a sub-ability of executive function and plays an important role in the entire cognitive process. However, declines in inhibitory control during aging significantly impair the quality of life of elderly people. Investigating methods to delay the decline of inhibitory control has become a focal point in current research. Tai Chi Chuan (TCC) is one effective method used to delay cognitive declines in older adults. However, the specific effects of TCC on inhibitory control and the mechanisms through which TCC may improve cognition in older adults have not been comprehensively investigated. Objective: The study explores possible neurological mechanisms related to the effects of TCC interventions on inhibitory control in older people using a functional near-infrared spectroscopy (fNIRS) technique and reaction times (RTs). Methods: A total of 26 healthy, elderly people who had not received TCC training completed all study procedures. The subjects were randomized to either the TCC group or the control group. Subjects in the TCC group were taught TCC by a certified instructor and trained for 8 weeks. The control group continued to perform general daily activities. The Flanker task was administered to every participant to evaluate inhibitory control preand post-intervention. While participants were performing the Flanker task, fNIRS data were collected. Results: Post-intervention, significant differences for incongruent flankers were found only for the TCC intervention group. Faster RTs were observed for the incongruent flankers in the TCC group than in the control group (p < 0.05). Analysis of the fNIRS data revealed an increase in oxy-Hb in the prefrontal cortex during the incongruent flankers after the TCC exercise intervention. Conclusion: The TCC intervention significantly improved inhibitory control in older adults, suggesting that TCC is an effective, suitable exercise for improving executive function and neurological health in elderly people.
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