Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell ...lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.
Low detection and nonadherence are major problems in current management approaches for patients with suspected atrial fibrillation (AF). Mobile health devices may enable earlier AF detection and ...improved AF management.
This study sought to investigate the effectiveness of AF screening in a large population-based cohort using smart device–based photoplethysmography (PPG) technology, combined with a clinical care AF management pathway using a mobile health approach.
AF screening was performed with smart devices using PPG technology, which were made available for the population ≥18 years of age across China. Monitoring for at least 14 days with a wristband (Honor Band 4) or wristwatch (Huawei Watch GT, Honor Watch, Huawei Technologies Co., Ltd., Shenzhen, China) was allowed. The patients with “possible AF” episodes using the PPG algorithm were further confirmed by health providers among the MAFA (mobile AF app) Telecare center and network hospitals, with clinical evaluation, electrocardiogram, or 24-h Holter monitoring.
There were 246,541 individuals who downloaded the PPG screening app, and 187,912 individuals used smart devices to monitor their pulse rhythm between October 26, 2018, and May 20, 2019. Among those with PPG monitoring (mean age 35 years, 86.7% male), 424 (of 187,912, 0.23%) (mean age 54 years, 87.0% male) received a “suspected AF” notification. Of those effectively followed up, 227 individuals (of 262, 87.0%) were confirmed as having AF, with the positive predictive value of PPG signals being 91.6% (95% confidential interval CI: 91.5% to 91.8%). Both suspected AF and identified AF markedly increased with age (p for trend <0.001), and individuals in Northeast China had the highest proportion of detected AF of 0.28% (95% CI: 0.20% to 0.39%). Of the individuals with identified AF, 216 (of 227, 95.1%) subsequently entered a program of integrated AF management using a mobile AF application; approximately 80% of high-risk patients were successfully anticoagulated.
Based on the present study, continuous home monitoring with smart device–based PPG technology could be a feasible approach for AF screening. This would help efforts at screening and detection of AF, as well as early interventions to reduce stroke and other AF-related complications. (Mobile Health mHealth Technology for Improved Screening, Patient Involvement and Optimizing Integrated Care in Atrial Fibrillation MAFA II; ChiCTR-OOC-17014138)
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Transforming growth factor beta (TGF‐β) plays an important role in the viral liver disease progression via controlling viral propagation and mediating inflammation‐associated responses. However, the ...antiviral activities and mechanisms of TGF‐β isoforms, including TGF‐β1, TGF‐β2 and TGF‐β3, remain unclear. Here, we demonstrated that all of the three TGF‐β isoforms were increased in Huh7.5 cells infected by hepatitis C virus (HCV), but in turn, the elevated TGF‐β isoforms could inhibit HCV propagation with different potency in infectious HCV cell culture system. TGF‐β isoforms suppressed HCV propagation through interrupting several different stages in the whole HCV life cycle, including virus entry and intracellular replication, in TGF‐β/SMAD signalling pathway–dependent and TGF‐β/SMAD signalling pathway–independent manners. TGF‐β isoforms showed additional anti‐HCV activities when combined with each other. However, the elevated TGF‐β1 and TGF‐β2, not TGF‐β3, could also induce liver fibrosis with a high expression of type I collagen alpha‐1 and α‐smooth muscle actin in LX‐2 cells. Our results showed a new insight into TGF‐β isoforms in the HCV‐related liver disease progression.
Plant-pathogen interactions induce a signal transmission series that stimulates the plant's host defense system against pathogens and this, in turn, leads to disease resistance responses. Plant ...innate immunity mainly includes two lines of the defense system, called pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). There is extensive signal exchange and recognition in the process of triggering the plant immune signaling network. Plant messenger signaling molecules, such as calcium ions, reactive oxygen species, and nitric oxide, and plant hormone signaling molecules, such as salicylic acid, jasmonic acid, and ethylene, play key roles in inducing plant defense responses. In addition, heterotrimeric G proteins, the mitogen-activated protein kinase cascade, and non-coding RNAs (ncRNAs) play important roles in regulating disease resistance and the defense signal transduction network. This paper summarizes the status and progress in plant disease resistance and disease resistance signal transduction pathway research in recent years; discusses the complexities of, and interactions among, defense signal pathways; and forecasts future research prospects to provide new ideas for the prevention and control of plant diseases.
Noble metal nanoparticles (NMNPs), which spring up like mushrooms, are gaining momentum owing to their unique physicochemical characteristics. Cucurbiturils, a class of synthetic macrocycles with ...intriguing and peculiar host–guest properties, have stimulated tremendous research interest in recent years. The marriage of NMNPs with cucurbiturils is expected to integrate and enhance the excellent characteristics of both components, e.g., precisely controlled particle size, stability, assembly, surface functionality, biocompatibility, tunable optical properties, and high catalytic activities. This review systematically outlines the recent progress on the fabricating strategies and important applications of cucurbiturils‐mediated NMNPs in sensing, surface‐enhanced Raman scattering, theranostics, and catalysis. A brief outlook on the future development of cucurbiturils‐mediated NMNPs is also presented.
Cucurbiturils not only endow noble metal nanoparticles (NMNPs) with exciting new and outstanding properties, but also significantly improve their original performance. The fabricating strategies of cucurbiturils‐mediated NMNPs for sensing, surface‐enhanced Raman scattering, theranostics, and catalysis are thoroughly overviewed, and the development prospects and challenges of cucurbiturils‐mediated NMNPs are also discussed.
Tea (Camellia sinensis L.) is a popular world beverage, and propagation of tea plants chiefly depends on the formation of adventitious roots in cuttings. To better understand potential mechanisms ...involved in adventitious root formation, we performed transcriptome analysis of single nodal cuttings of C. sinensis treated with or without indole-3-butyric acid (IBA) using the Illumina sequencing method. Totally 42.5 million RNA-Seq reads were obtained and these were assembled into 59,931 unigenes, with an average length of 732 bp and an N50 of 1292 bp. In addition, 1091 differentially expressed unigenes were identified in the tea cuttings treated with IBA compared to controls, including 656 up- and 435 down-regulated genes. Further real time RT-PCR analysis confirmed RNA-Seq data. Functional annotation analysis showed that many genes were involved in plant hormone signal transduction, secondary metabolism, cell wall organization and glutathione metabolism, indicating potential contributions to adventitious rooting. Our study presents a global view of transcriptome profiles of tea cuttings in response to IBA treatment and provides new insights into the fundamental mechanisms associated with auxin-induced adventitious rooting. Our data will be a valuable resource for genomic research about adventitious root formation in tea cuttings, which can be used to improve rooting for difficult-to-root varieties.
Summary
Brassica napus L. is an important oil crop worldwide and is the main raw material for biofuel. Seed weight and seed size are the main contributors to seed yield. DA1 (DA means big in Chinese) ...is an ubiquitin receptor and negatively regulates seed size. Down‐regulation of AtDA1 in Arabidopsis leads to larger seeds and organs by increasing cell proliferation in integuments. In this study, BnDA1 was down‐regulated in B. napus by over expressed of AtDA1R358K, which is a functional deficiency of DA1 with an arginine‐to‐lysine mutation at the 358th amino acid. The results showed that the biomass and size of the seeds, cotyledons, leaves, flowers and siliques of transgenic plants all increased significantly. In particular, the 1000 seed weight increased 21.23% and the seed yield per plant increased 13.22% in field condition. The transgenic plants had no negative traits related to yield. The candidate gene association analysis demonstrated that the BnDA1 locus was contributed to the seeds weight. Therefore, our study showed that regulation of DA1 in B. napus can increase the seed yield and biomass, and DA1 is a promising target for crop improvement.
We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the ...top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10(-11), OR = 1.21; rs4227, P = 4.31 × 10(-10), OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10(-14), OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10(-20), OR = 1.34; rs1794275, P = 3.43 × 10(-13), OR = 1.30; rs2523946, P = 1.74 × 10(-11), OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10(-11), OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.
Incorporating synthetic macrocycles with unique structures and distinct conformations into conjugated macrocycle polymers (CMPs) can endow the resulting materials with great potentials in gas uptake ...and pollutant adsorption. Here, four CMPs (CMP‐n, n=1–4) capable of reversibly capturing iodine and efficiently separating carbon dioxide are constructed from per‐triflate functionalized leaning tower6arene (LT6‐OTf) and 2biphenyl‐extended pillar6arene (BpP6‐OTf) via Pd‐catalyzed Sonogashira–Hagihara cross‐coupling reaction. Intriguingly, owing to the appropriate cavity size of LT6‐OTf and the numerous aromatic rings in the framework, the newly designed CMP‐4 possesses an outstanding I2 affinity with a large uptake capacity of 208 wt % in vapor and a great removal efficiency of 94 % in aqueous solutions. To our surprise, with no capacity to accommodate nitrogen, CMP‐2 constructed from BpP6‐OTf is able to specifically capture carbon dioxide at ambient conditions.
Four catcher‐type conjugated macrocycle polymers (CMP‐n, n=1–4) have been designed and synthesized successfully, exhibiting interesting application in CO2 and I2 uptake. The CMP‐2 is able to capture CO2 with excellent selectivity and the CMP‐4 is capable of adsorbing iodine with outstanding capacity.
To identify susceptibility loci for schizophrenia, we performed a two-stage genome-wide association study (GWAS) of schizophrenia in the Han Chinese population (GWAS: 746 individuals with ...schizophrenia and 1,599 healthy controls; validation: 4,027 individuals with schizophrenia and 5,603 healthy controls). We identified two susceptibility loci for schizophrenia at 6p21-p22.1 (rs1233710 in an intron of ZKSCAN4, P(combined) = 4.76 × 10(-11), odds ratio (OR) = 0.79; rs1635 in an exon of NKAPL, P(combined) = 6.91 × 10(-12), OR = 0.78; rs2142731 in an intron of PGBD1, P(combined) = 5.14 × 10(-10), OR = 0.79) and 11p11.2 (rs11038167 near the 5' UTR of TSPAN18, P(combined) = 1.09 × 10(-11), OR = 1.29; rs11038172, P(combined) = 7.21 × 10(-10), OR = 1.25; rs835784, P(combined) = 2.73 × 10(-11), OR = 1.27). These results add to previous evidence of susceptibility loci for schizophrenia at 6p21-p22.1 in the Han Chinese population. We found that NKAPL and ZKSCAN4 were expressed in postnatal day 0 (P0) mouse brain. These findings may lead to new insights into the pathogenesis of schizophrenia.
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