Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
787,949
result(s) for
"Yang, T"
Sort by:
Recurrently deregulated lncRNAs in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples’ RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as
HAND2-AS1
, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.
Long noncoding-RNAs have been linked to hepatocellular carcinoma (HCC) and some can be used as prognostic markers. Here the authors, by analysing RNA-seq in 60 clinical samples from 20 patients, provide a resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.
Journal Article
Long-term risk of radionecrosis and imaging changes after stereotactic radiosurgery for brain metastases
Radionecrosis is a well-characterized effect of stereotactic radiosurgery (SRS) and is occasionally associated with serious neurologic sequelae. Here, we investigated the incidence of and clinical variables associated with the development of radionecrosis and related radiographic changes after SRS for brain metastases in a cohort of patients with long-term follow up. 271 brain metastases treated with single-fraction linear accelerator-based SRS were analyzed. Radionecrosis was diagnosed either pathologically or radiographically. Univariate and multivariate Cox regression was performed to determine the association between radionecrosis and clinical factors available prior to treatment planning. After median follow up of 17.2 months, radionecrosis was observed in 70 (25.8 %) lesions, including 47 (17.3 %) symptomatic cases. 22 of 70 cases (31.4 %) were diagnosed pathologically and 48 (68.6 %) were diagnosed radiographically. The actuarial incidence of radionecrosis was 5.2 % at 6 months, 17.2 % at 12 months and 34.0 % at 24 months. On univariate analysis, radionecrosis was associated with maximum tumor diameter (HR 3.55, p < 0.001), prior whole brain radiotherapy (HR 2.21, p = 0.004), prescription dose (HR 0.56, p = 0.02) and histology other than non-small cell lung, breast or melanoma (HR 1.85, p = 0.04). On multivariate analysis, only maximum tumor diameter (HR 3.10, p < 0.001) was associated with radionecrosis risk. This data demonstrates that with close imaging follow-up, radionecrosis after single-fraction SRS for brain metastases is not uncommon. Maximum tumor diameter on pre-treatment MR imaging can provide a reliable estimate of radionecrosis risk prior to treatment planning, with the greatest risk among tumors measuring >1 cm.
Journal Article
Multicomponent intermetallic nanoparticles and superb mechanical behaviors of complex alloys
Improving the strength of a metal alloy is hard to do without sacrificing the ductility. Yang et al. designed an iron-nickel-cobalt (Fe-Ni-Co) alloy laced with aluminum-titanium (Al-Ti) nanoparticles with both high strength and ductility. The key was getting the composition tuned correctly, because the Fe-Ni-Co matrix reacts with the Al-Ti nanoparticles. This was vital for avoiding environmental embrittlement, enhancing work hardening, and improving ductility. Science , this issue p. 933 Multicomponent nanoparticles enhance both the strength and ductility of an iron-nickel-cobalt alloy. Alloy design based on single–principal-element systems has approached its limit for performance enhancements. A substantial increase in strength up to gigapascal levels typically causes the premature failure of materials with reduced ductility. Here, we report a strategy to break this trade-off by controllably introducing high-density ductile multicomponent intermetallic nanoparticles (MCINPs) in complex alloy systems. Distinct from the intermetallic-induced embrittlement under conventional wisdom, such MCINP-strengthened alloys exhibit superior strengths of 1.5 gigapascals and ductility as high as 50% in tension at ambient temperature. The plastic instability, a major concern for high-strength materials, can be completely eliminated by generating a distinctive multistage work-hardening behavior, resulting from pronounced dislocation activities and deformation-induced microbands. This MCINP strategy offers a paradigm to develop next-generation materials for structural applications.
Journal Article
Dual heterogeneous structures lead to ultrahigh strength and uniform ductility in a Co-Cr-Ni medium-entropy alloy
Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1
2
-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1
2
nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.
Improving both strength and ductility simultaneously in structural metals and alloys remains a challenge. Here, the authors design a heterogeneous structure in a Co-Cr-Ni alloy that results in ultrahigh strength and significant uniform elongation.
Journal Article
Superresolution Pattern Recognition Reveals the Architectural Map of the Ciliary Transition Zone
The transition zone (TZ) of primary cilia serves as a diffusion barrier to regulate ciliogenesis and receptor localization for key signaling events such as sonic hedgehog signaling. Its gating mechanism is poorly understood due to the tiny volume accommodating a large number of ciliopathy-associated molecules. Here we performed stimulated emission depletion (STED) imaging of collective samples and recreated superresolved relative localizations of eight representative species of ciliary proteins using position averages and overlapped with representative electron microscopy (EM) images, defining an architectural foundation at the ciliary base. Upon this framework, transmembrane proteins TMEM67 and TCTN2 were accumulated at the same axial level as MKS1 and RPGRIP1L, suggesting that their regulation roles for tissue-specific ciliogenesis occur at a specific level of the TZ. CEP290 is surprisingly localized at a different axial level bridging the basal body (BB) and other TZ proteins. Upon this molecular architecture, two reservoirs of intraflagellar transport (IFT) particles, correlating with phases of ciliary growth, are present: one colocalized with the transition fibers (TFs) while the other situated beyond the distal edge of the TZ. Together, our results reveal an unprecedented structural framework of the TZ, facilitating our understanding in molecular screening and assembly at the ciliary base.
Journal Article
Predicting changes in protein thermodynamic stability upon point mutation with deep 3D convolutional neural networks
Predicting mutation-induced changes in protein thermodynamic stability (ΔΔG) is of great interest in protein engineering, variant interpretation, and protein biophysics. We introduce ThermoNet, a deep, 3D-convolutional neural network (3D-CNN) designed for structure-based prediction of ΔΔGs upon point mutation. To leverage the image-processing power inherent in CNNs, we treat protein structures as if they were multi-channel 3D images. In particular, the inputs to ThermoNet are uniformly constructed as multi-channel voxel grids based on biophysical properties derived from raw atom coordinates. We train and evaluate ThermoNet with a curated data set that accounts for protein homology and is balanced with direct and reverse mutations; this provides a framework for addressing biases that have likely influenced many previous ΔΔG prediction methods. ThermoNet demonstrates performance comparable to the best available methods on the widely used S sym test set. In addition, ThermoNet accurately predicts the effects of both stabilizing and destabilizing mutations, while most other methods exhibit a strong bias towards predicting destabilization. We further show that homology between S sym and widely used training sets like S2648 and VariBench has likely led to overestimated performance in previous studies. Finally, we demonstrate the practical utility of ThermoNet in predicting the ΔΔGs for two clinically relevant proteins, p53 and myoglobin, and for pathogenic and benign missense variants from ClinVar. Overall, our results suggest that 3D-CNNs can model the complex, non-linear interactions perturbed by mutations, directly from biophysical properties of atoms.
Journal Article
Metastasis-directed therapy for oligometastasis and beyond
Metastasis-directed therapy (MDT)—local therapy that is intended to eradicate specific metastatic lesions—has hitherto been used with varying degrees of clinical efficacy and acceptance as a meaningful therapy for metastatic disease. Over the past 25 years, however, the momentum for using MDT to manage patients with metastatic solid tumours has increased, driven by several factors. Among these factors is the recognition that patients with limited metastatic burden could potentially derive survival benefits from MDT. Furthermore, although current systemic therapies are increasingly effective, they are infrequently curative. In addition, technological advances have broadened the spectrum of metastatic lesions that can be treated with ablative intent. Here we aim to briefly review the status of evidence for the clinical benefit of MDT based on current data mainly from trials in patients with oligometastatic disease, discuss the myriad of clinical states that might fall under and beyond the definition of oligometastasis, review technological advances in MDT and their applications beyond oligometastasis, and discuss the need for the continued co-evolution of MDT and systemic therapy as we seek to understand which patients with metastatic cancer can achieve durable remission and how to optimally manage those who cannot.
Journal Article
Autoimmune Lymphoproliferative Syndrome: An Overview
Autoimmune lymphoproliferative syndrome (ALPS) is an inherited nonmalignant lymphoproliferative disorder characterized by heterozygous mutations within the first apoptosis signal receptor (FAS) signaling pathway. Defects in FAS-mediated apoptosis cause an expansion and accumulation of autoreactive CD4− and CD8− (double-negative) T cells, leading to cytopenias, splenomegaly, lymphadenopathy, autoimmune disorders, and a greatly increased lifetime risk of lymphoma. The differential diagnosis of ALPS includes infection, other inherited immunodeficiency disorders, primary and secondary autoimmune syndromes, and lymphoma. The most consistent pathologic feature is a florid paracortical expansion of double-negative T cells in lymph nodes. A presumptive clinical diagnosis can be made from symptoms and a constellation of laboratory test results. However, a definitive diagnosis requires ancillary testing and enables disease subclassification. Recognition of ALPS is critical, as treatment with immunosuppressive therapies can effectively reduce or ameliorate symptoms for most patients.
Journal Article
Formation and evolution mechanism of regional haze: a case study in the megacity Beijing, China
The main objective of this study is to investigate the formation and evolution mechanism of the regional haze in megacity Beijing by analyzing the process of a severe haze that occurred 20–27 September 2011. Mass concentration and size distribution of aerosol particles as well as aerosol optical properties were concurrently measured at the Beijing urban atmospheric environment monitoring station. Gaseous pollutants (SO2, NO-NO2-NOx, O3, CO) and meteorological parameters (wind speed, wind direction, and relative humidity) were simultaneously monitored. Meanwhile, aerosol spatial distribution and the height of planetary boundary layer (PBL) were retrieved from the signal of satellite and LIDAR (light detection and ranging). Concentrations of NO, NO2, SO2, O3, and CO observed during 23–27 September had exceeded the national ambient air quality standards for residents. The mass concentration of PM2.5 gradually accumulated during the measurement and reached at 220 μg m−3 on 26 September, and the corresponding atmospheric visibility was only 1.1 km. The daily averaged AOD in Beijing increased from ~ 0.16 at λ = 500 nm on 22 September and reached ~ 3.5 on 26 September. The key factors that affected the formation and evolution of this haze episode were stable anti-cyclone synoptic conditions at the surface, decreasing of the height of PBL, heavy pollution emissions from urban area, number and size evolution of aerosols, and hygroscopic growth for aerosol scattering. This case study may provide valuable information for the public to recognize the formation mechanism of the regional haze event over the megacity, which is also useful for the government to adopt scientific approach to forecast and eliminate the occurrence of regional haze in China.
Journal Article