Multi-scale integrative analyses identify THBS2+ cancer-associated fibroblasts as a key orchestrator promoting aggressiveness in early-stage lung adenocarcinoma.

Rationale: Subsets of patients with early-stage lung adenocarcinoma (LUAD) have a poor post-surgical course after curative surgery. However, biomarkers stratifying this high-risk subset and molecular underpinnings underlying the aggressive phenotype remain unclear. Methods: We integrated bulk and single-cell transcriptomics, proteomics, secretome and spatial profiling of clinical early-stage LUAD samples to identify molecular underpinnings that promote the aggressive phenotype. Results: We identified and validated THBS2, at multi-omic levels, as a tumor size-independent biomarker that robustly predicted post-surgical survival in multiple independent clinical cohorts of early-stage LUAD. Furthermore, scRNA-seq data revealed that THBS2 is exclusively derived from a specific cancer-associated fibroblast (CAF) subset that is distinct from CAFs defined by classical markers. Interestingly, our data demonstrated that THBS2 was preferentially secreted via exosomes in early-stage LUAD tumors with high aggressiveness, and its levels in the peripheral plasma associated with short recurrence-free survival. Further characterization showed that THBS2-high early-stage LUAD was characterized by suppressed antitumor immunity. Specifically, beyond tumor cells, THBS2+ CAFs mainly interact with B and CD8+ T lymphocytes as well as macrophages within tumor microenvironment of early-stage LUAD, and THBS2-high LUAD was associated with decreased immune cell infiltrates but increased immune exhaustion marker. Clinically, high THBS2 expression predicted poor response to immunotherapies and short post-treatment survival of patients. Finally, THBS2 recombinant protein suppressed ex vivo T cells proliferation and promoted in vivo LUAD tumor growth and distant micro-metastasis. Conclusions: Our multi-level analyses uncovered tumor-specific THBS2+ CAFs as a key orchestrator promoting aggressiveness in early-stage LUAD

Designing Delay Lines Based on the SD/DE Algorithm for Transmitted-Reference Ultra-Wideband Systems

Hong Kong Research Grants Council [CityU1117/10E]; NSF of China [60972053]This paper studies the design problem of delay lines in Transmitted-Reference Ultra-Wideband (TR-UWB) systems based on a new evolutionary scheme named Stepping-Dichotomy/Differential-Evolution (SD/DE) algorithm. The group delay response, required for the pass-band as an objective of the delay line, is approximated by using a new nonlinear optimization method under a maximin criterion. The procedure is rather generic, applicable to arbitrary bandwidths, delays, and distortions. Moreover, the approach is very convenient for calculating the least-order delay line, therefore especially suitable for real applications

Channel modeling of vehicle detection system for UWB communication

Conference Name:2012 International Conference on Manufacturing Engineering and Process, ICMEP 2012. Conference Address: Kunming, China. Time:April 21, 2012 - April 22, 2012.In this paper, a new channel model through ultra-wideband (UWB) communication for vehicle detection system (VDS) is proposed. The Gauss 2st derivative function is used as the transmitted signal and the received signal is evaluated. The main objective of this work is to provide an analytical approach for obtaining the main parameters under new channel through the bodywork structure properties. The characteristic of the RMS delay spread is discussed in this paper. 漏 (2012) Trans Tech Publications

Loss of Hsp90 Association Up-Regulates Src-Dependent ErbB2 Activity

The receptor tyrosine kinase ErbB2 plays a crucial role in tumorigenesis. We showed previously that the molecular chaperone Hsp90 protects ErbB2 from proteasome-mediated degradation by binding to a short loop structure in the N-lobe of the kinase domain. Here we show that loss of Hsp90 binding correlates with enhanced ErbB2 kinase activity and its transactivating potential, concomitant with constitutively increased phosphorylation of Tyr877, located in the activation loop of the kinase domain. We show further that Tyr877 phosphorylation is mediated by Src and that it is necessary for the enhanced kinase activity of ErbB2. Finally, computer modeling of the kinase domain suggests a phosphorylation-dependent reorientation of the activation loop, denoting the importance of Tyr877 phosphorylation for ErbB2 activity. These findings suggest that Hsp90 binding to ErbB2 participates in regulation of kinase activity as well as kinase stability

Expression and clinical significance of Claudin-1 and Claudin-3 in the serum of patients with psoriasis vulgaris

Objective To investigate the expression and clinical significance of serum Claudin-1 and Claudin-3 levels in patients with psoriasis vulgaris (PV). Methods A total of 122 patients with PV were enrolled as the PV group (including 36 cases in the mild group, 54 cases in the moderate group, 32 cases in the severe group), and 60 healthy controls were enrolled from the physical examination center. The serum levels of hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin6 (IL-6), Claudin-1 and Claudin-3 were measured using enzyme linked immunosorbent assay (ELISA). Logistic regression was used to analyze the relationship between serum levels of Claudin-1 and Claudin-3 and PV severity, and the receiver operating characteristic (ROC) curve was used to analyze its diagnostic value. Results The levels of hs-CRP, TNF-α and IL-6 in PV group were significantly higher than that in the controls (P<0.05). The serum levels of Claudin-1 in the PV group were significantly lower than that in the controls (t=11.96, P<0.001), while the serum levels of Claudin-3 was significantly higher in the PV group (t=10.64, P<0.001). The serum levels of Claudin-1 were negatively correlated with disease severity (r=-0.38), hs-CRP (r=-0.18) and TNF-α levelsm(r=-0.22) (all P<0.05). In contrast, serum levels of Claudin-3 were positively correlated with disease severity (r=0.41), and serum levels of hs-CRP (r=0.20), TNF-α (r=0.18) and IL-6 (r=0.36) (all P<0.05). Moreover, serum levels of Claudin-1 were negatively correlated with Claudin-3 (r=-0.22, P=0.015). The areas under the curve of Claudin-1 and Claudin-3 for the diagnosis of PV were 0.875 and 0.867, respectively, which were significantly higher than that of TNF-α (Z values were 4.16 and 3.60, respectively, P<0.001) and IL-6 (Z values were 3.63, 3.52, respectively, P<0.001). Conclusions The altered expression levels of serum Claudin-1 and Claudin-3 in PV patients are associated with disease severity and the levels of inflammatory markers. Alterations of Claudin-1 and Claudin-3 expression are independent risk factors for PV. Serum levels of Claudin-1 and Claudin-3 have some diagnostic value for PV

Error performance analysis of opportunistic relaying system based on DCSK

Conference Name:11th IEEE International Conference on Trust, Security and Privacy in Computing and Communications, TrustCom-2012. Conference Address: Liverpool, United kingdom. Time:June 25, 2012 - June 27, 2012.University of Bradford; IEEE Technical Committee on Scalable Computing (TCSC); IEEE; IEEE Computer SocietyIn this paper, a differential chaos shift keying (DCSK) opportunistic relaying scheme is proposed and the system performance is analyzed over multipath Rayleigh fading channel, where all the relays adopt decode-and-forward (DF) strategy. Considering the effect of the path loss, the best relay is chosen by max-min selection criterion. We derive the probability density function (PDF) of the signal noise ratio (SNR) in each hop, and give the expression of the end-to-end bit error rate (BER). The effects of the number of relays, the propagation distance and the spread-spectrum factor on the system performance are investigated. It is shown that the BER performances are proportional to the number of relays and the propagation distance, while they are inverse ratio to the spread-spectrum factor. Numerical results prove an excellent match between simulations and our analysis expressions. 漏 2012 IEEE

Parotid tumors and their postoperative complications: A 5-year experience

Introduction: Understanding the pathophysiology, clinical characteristics, and postoperative complications of parotid tumors is crucial in light of the growing emphasis on the occurrence and development of parotid tumor disease. Materials and methods: The study population consisted of 387 cases of primary parotid tumors treated surgically at our institution between July 2015 and November 2020. We statistically analyzed the gender, age, and pathological findings of patients, 307 of whom underwent postoperative return visits and were included in the study of postoperative complications. Results: The ratio of male to female parotid tumor patients was 1.39:1, and the best possible age range was between 51 and 60 years. The percentage of benign to malignant tumors (342/45) was 7.6:1. Pleomorphic adenoma constituted the majority of benign tumors. Adenoid cystic carcinoma constituted the majority of malignant tumors.The sensory deficit of the auricle, salivary fistula, facial nerve paralysis, and Frey's syndrome were the most prevalent postoperative complications of parotid tumors. Conclusions: Our efforts should focus on active prevention and treating parotid tumor postoperative complications

Differences between Kazak Cheeses Fermented by Single and Mixed Strains Using Untargeted Metabolomics

Mixed fermentation improves the flavor quality of food. Untargeted metabolomics were used to evaluate the impact of mixed fermentation and single-strain fermentation on the volatile and non-volatile compound profiles of Kazak cheese. Lacticaseibacillus paracasei SMN-LBK and Kluyveromyces marxianus SMN-S7-LBK were used to make mixed-fermentation cheese (M), while L. paracasei SMN-LBK was applied in single-strain-fermentation cheese (S). A higher abundances of acids, alcohols, and esters were produced via mixed fermentation. Furthermore, 397 differentially expressed non-volatile metabolites were identified between S and M during ripening. The flavor compounds in mixed-fermentation cheese mainly resulted from ester production (ethyl butanoate, ethyl acetate, ethyl octanoate, and ethyl hexanoate) and amino acid biosynthesis (Asp, Glu, Gln, and Phe). The metabolites were differentially expressed in nitrogen metabolism, D-glutamine and D-glutamate metabolism, phenylalanine metabolism, D-alanine metabolism, and other metabolic pathways. The amount of flavor compounds was increased in M, indicating that L. paracasei SMN- LBK and K. marxianus SMN-S7-LBK had synergistic effects in the formation of flavor compounds. This study comprehensively demonstrated the difference in metabolites between mixed-fermentation and single-strain-fermentation cheese and provided a basis for the production of Kazak cheese with diverse flavor characteristics

Transcriptome Analysis of mRNA and miRNA in Somatic Embryos of Larix leptolepis Subjected to Hydrogen Treatment

Hydrogen is a therapeutic antioxidant that has been used extensively in clinical trials. It also acts as a bioactive molecule that can alleviate abiotic stress in plants. However, the biological effects of hydrogen in somatic embryos and the underlying molecular basis remain largely unknown. In this study, the morphological and physiological influence of exogenous H2 treatment during somatic embryogenesis was characterized in Larix leptolepis Gordon. The results showed that exposure to hydrogen increased the proportions of active pro-embryogenic cells and normal somatic embryos. We sequenced mRNA and microRNA (miRNA) libraries to identify global transcriptome changes at different time points during H2 treatment of larch pro-embryogenic masses (PEMs). A total of 45,393 mRNAs and 315 miRNAs were obtained. Among them, 4253 genes and 96 miRNAs were differentially expressed in the hydrogen-treated libraries compared with the control. Further, a large number of the differentially expressed mRNAs and miRNAs were related to reactive oxygen species (ROS) homeostasis and cell cycle regulation. We also identified 4399 potential target genes for 285 of the miRNAs. The differential expression data and the mRNA-miRNA interaction network described here provide new insights into the molecular mechanisms that determine the performance of PEMs exposed to H2 during somatic embryogenesis