Label-free detection of exosomes from different cellular sources based on surface-enhanced Raman spectroscopy combined with machine learning models

Exosomes are significant facilitators of inter-cellular communication that can unveil cell-cell interactions, signaling pathways, regulatory mechanisms and disease diagnostics. Nonetheless, current analysis required large amount of data for exosome identification that it hampers efficient and timely mechanism study and diagnostics. Here, we used a machine-learning assisted Surface-enhanced Raman spectroscopy (SERS) method to detect exosomes derived from six distinct cell lines (HepG2, Hela, 143B, LO-2, BMSC, and H8) with small amount of data. By employing sodium borohydride-reduced silver nanoparticles and sodium borohydride solution as an aggregating agent, 100 SERS spectra of the each types of exosomes were collected and then subjected to multivariate and machine learning analysis. By integrating Principal Component Analysis with Support Vector Machine (PCA-SVM) models, our analysis achieved a high accuracy rate of 94.4% in predicting exosomes originating from various cellular sources. In comparison to other machine learning analysis, our method used small amount of SERS data to allow a simple and rapid exosome detection, which enables a timely subsequent study of cell-cell interactions, communication mechanisms, and disease mechanisms in life sciences.Comment: 5 figure

The \u3ci\u3eAPOA5\u3c/i\u3e rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women

Background: The APOA5 rs662799 polymorphism has been widely reported regarding its associations with the plasma lipid levels and the occurrence of coronary heart disease (CHD), whereas its relationship with the severity of CHD has not yet been explored. Methods: Four hundred and seventy-eight angiografically defined subjects (325 CHD patients and 153 CHD-free controls) were enrolled in this study. The rs662799 polymorphism was genotyped, and the fasting lipid data were collected for all participants. The severity of CHD was evaluated for the CHD patients by using Gensini scores. Results: The variant C allele of the rs662799 polymorphism was associated with lower levels of HDL-C in CHD-free women, and higher levels of TG and TG/HDL-C in women with CHD (P \u3c 0.05 for all). The C allele was associated with higher prevalence of dyslipidemia and higher levels of Gensini scores only in women (P \u3c 0.05 for both), but not in men. Multivariate linear regression analysis showed that the rs662799 polymorphism was independently associated with the Gensini scores in women after adjustment for other potential CHD risk factors (Beta = 0.157, 95 % CI: 0.017–0.298, P = 0.028). Conclusion: Our data indicate that the rs662799 polymorphism is associated with dyslipidemia and the severity of CHD in Chinese women

Design Multilayer Antireflection Coatings for Terrestrial Solar Cells

In order to analyze the influence of methods to design antireflection coatings (ARCs) on reflectivity of broadband solar cells, we provide detailed analyses about the ARC coupled with a window layer and the refractive index dispersion effect of each layer. By multidimensional matrix data simulation, two methods were employed to measure the composite reflection of a Si/ZnS double-layer ARC within the spectral ranges of 300–870 nm (dual junction) and 300–1850 nm (triple junction) under AM1.5 solar radiation. A comparison study, between the results obtained from the commonly used weighted average reflectance method (WAR) and that from the introduced effective average reflectance method (EAR), shows that the optimization of ARC by EAR method is convenient and feasible

An epigenetic switch induced by Shh signalling regulates gene activation during development and medulloblastoma growth

The Sonic hedgehog (Shh) signalling pathway plays important roles during development and in cancer. Here we report a Shh-induced epigenetic switch that cooperates with Gli to control transcription outcomes. Before induction, poised Shh target genes are marked by a bivalent chromatin domain containing a repressive histone H3K27me3 mark and an active H3K4me3 mark. Shh activation induces a local switch of epigenetic cofactors from the H3K27 methyltransferase polycomb repressive complex 2 (PRC2) to an H3K27me3 demethylase Jmjd3/Kdm6b-centred coactivator complex. We also find that non-enzymatic activities of Jmjd3 are important and that Jmjd3 recruits the Set1/MLL H3K4 methyltransferase complexes in a Shh-dependent manner to resolve the bivalent domain. In vivo, changes of the bivalent domain accompanied Shh-activated cerebellar progenitor proliferation. Overall, our results reveal a regulatory mechanism that underlies the activation of Shh target genes and provides insight into the causes of various diseases and cancers exhibiting altered Shh signalling

Genetic and biochemical studies of disulfide bond isomerization in Escherichia coli

textHeterologous proteins containing multiple disulfide bonds cannot fold efficiently when expressed in secreted form in Escherichia coli bacteria. The rate-limiting step in the folding of multidisulfide proteins in bacteria is the rearrangement of incorrect disulfide bonds, a process catalyzed by disulfide isomerases. Two strategies for enhancing disulfide bond isomerization in E. coli were investigated: (i) Co-expression of eukaryotic disulfide isomerases; (ii) Isolation of chromosomal lesions that improve the folding of the complex eukaryotic enzyme tissue plasminogen activator (tPA) which contains 17 disulfide bonds. The co-expression of the yeast protein disulfide isomerase (PDI) was found to increase the yield of native bovine pancreatic trypsin inhibitor by 2-fold, similar to the effect previously seen with the co-expression of the rat PDI. It was also shown that co-expression of yeast PDI was more effective than that of rat PDI in facilitating the expression of active tPA in E. coli periplasm. A novel genetic screen was designed and used to identify E. coli mutants that enhanced the production of active tPA. Nine mutant strains that exhibited significantly higher disulfide isomerization activity were isolated. All mutants showed markedly elevated DsbC protein expression. Unexpectedly, in eight out of the nine mutants, the upregulation of DsbC was mediated by defects in RNA processing by RNase E which is encoded by the rne gene: 5/9 mutations were allelic to rne whereas 3/9 were shown to exhibit impaired RNase E activity due to lesions in other loci. The importance in mRNA processing on the expression of DsbC is underscored by the half-life of the dsbC mRNA which is only 0.8 minutes at 37o C. The E.coli endonuclease RNase E is a 1061 amino acid protein that plays a dominant role in RNA degradation. RNase E consists of an N-terminal catalytic domain and a C-terminal half (CTH) region. The latter region serves as a scaffold for the binding of various proteins. It was found that MenG, which increases E. coli disulfide isomerization when it is overexpressed, negatively regulates RNase E enzymatic activity. It was further shown that this regulation depends on the presence of the RNase E CTH region and involves MenG-RNase E interaction.Ecology, Evolution and Behavio

L1-induced norm and controller synthesis of positive systems

In this paper, the problem of ?1?1-induced controller design for discrete-time positive systems is investigated with the use of linear Lyapunov function. An analytical method to compute the exact value of ?1?1-induced norm is first presented. Then, a novel characterization for stability and ?1?1-induced performance is proposed. Based on the characterization, a necessary and sufficient condition for the existence of desired controllers is derived, and an iterative convex optimization approach is developed to solve the condition. In addition, the synthesis of the state-feedback controller for single-input multiple-output (SIMO) positive systems is investigated. For this special case, an analytic solution is established to show how the optimal ?1?1-induced controller can be designed, and some links to the spectral radius of the closed-loop systems are provided. Finally, the theoretical results are illustrated through a numerical example