Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) ...metastasis and chemoresistance have not been fully characterized.
CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1.
CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients.
CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.
This randomized, double‐blind, placebo‐controlled study evaluated whether lamivudine given during late pregnancy can reduce hepatitis B virus (HBV) perinatal transmission in highly viraemic mothers. ...Mothers were randomized to either lamivudine 100 mg or placebo from week 32 of gestation to week 4 postpartum. At birth, infants received recombinant HBV vaccine with or without HBIg and were followed until week 52. One hundred and fifty mothers, with a gestational age of 26–30 weeks and serum HBV DNA >1000 MEq/mL (bDNA assay), were treated. A total of 141 infants received immunoprophylaxis at birth. In lamivudine‐treated mothers, 56 infants received vaccine + HBIg (lamivudine + vaccine + HBIg) and 26 infants received vaccine (lamivudine + vaccine). In placebo‐treated mothers, 59 infants received vaccine + HBIg (placebo + vaccine + HBIg). At week 52, in the primary analyses where missing data was counted as failures, infants in the lamivudine + vaccine + HBIg group had a significant decrease in incidence of HBsAg seropositivity (10/56, 18%vs 23/59, 39%; P = 0.014) and in detectable HBV DNA (11/56, 20%vs 27/59, 46%; P = 0.003) compared to infants in the placebo + vaccine + HBIg group. Sensitivity analyses to evaluate the impact of missing data at week 52 resulting from a high dropout rate (13% in the lamivudine + vaccine + HBIg group and 31% in the placebo + vaccine + HBIg group) remained consistent with the primary analysis in that lower transmission rates were still observed in the infants of lamivudine‐treated mothers, but the differences were not statistically significant. No safety concerns were noted in the lamivudine‐treated mothers or their infants. Results of this study suggest that lamivudine reduced HBV transmission from highly viraemic mothers to their infants who received passive/active immunization.
In the context of ancestral reconstruction, a phylogeny is often treated as though it were a known quantity (with Bayesian approaches being an important exception). Because there can be an enormous ...number of phylogenies that are nearly equally effective at explaining the data, reducing the subset of phylogenies supported by the data to a single representative, or point estimate, can be a convenient and sometimes necessary simplifying assumption. ...there are several web server-based applications that allow investigators to use ML methods for ancestral reconstruction of different character types without having to install any software.
The intrinsic magnetic topological insulatorMnBi2Te4exhibits rich topological effects such as quantum anomalous Hall effect and axion electrodynamics. Here, by combining the use of synchrotron and ...laser light sources, we carry out comprehensive and high-resolution angle-resolved photoemission spectroscopy studies onMnBi2Te4and clearly identify its topological electronic structure. In contrast to theoretical predictions and previous studies, we observe topological surface states with diminished gap forming a characteristic Dirac cone. We argue that the topological surface states are mediated by multidomains of different magnetization orientations. In addition, the temperature evolution of the energy bands clearly reveals their interplay with the magnetic phase transition by showing interesting differences between the bulk and surface states, respectively. The investigation of the detailed electronic structure ofMnBi2Te4and its temperature evolution provides important insight into not only the exotic properties ofMnBi2Te4, but also the generic understanding of the interplay between magnetism and topological electronic structure in magnetic topological quantum materials.
•Oxidative degradation of carbamazepine by Fe(II)/persulfate process is reported. CBZ degradation rate depends on pH value and the ratio of Fe2+:S2O82−:CBZ. The anions NO3−, SO42− and H2PO4− caused a ...negative effect on CBZ degradation.•The higher the Cl− concentration, the faster the CBZ decay rate.•The presence of Cl− influences the evolution profiles of various intermediates.
Experimental studies were conducted to investigate the oxidative degradation of carbamazepine (CBZ), one of the most frequently detected pharmaceuticals in various waters, by Fe(II)-activated persulfate process. Results show that the Fe2+/S2O82− process is very effective for the elimination of CBZ and characterized by a two-stage kinetics (a rapid initial decay followed by a retardation stage). CBZ degradation reaction was observed to be pH dependent and the optimum pH is 3.0 in the range of 2.00–7.87. The concentration of Fe2+ and S2O82− exhibited a noticeable influence on CBZ removal efficiency, where S2O82− exerted more significant effects than that of Fe2+. The optimal molar ratio of CBZ, Fe2+, and S2O82− is found to be 1:5:40. The effect of various inorganic anions on CBZ removal was also evaluated under the optimal conditions. The anions NO3−, SO42− and H2PO4-caused a negative effect on the performance of this process, while Cl− interestingly accelerated CBZ degradation. The higher the Cl− concentration, the faster the CBZ decay rate. The intermediates were identified during CBZ degradation with and without the presence of Cl−. The evolution of intermediates for these two scenarios was compared. The decay pathways of CBZ were proposed accordingly.
Currently, investigations on the microbiota of sports centers and related facilities have been carried out in some countries, which showed that Microsporum gypseum, Trichophyton mentagrophytes and T. ...tonsurans are important dermatoprotofungi. In China, some research on athletes and sports equipment between the fungal community and public health has made some interesting achievements. However, the bacterial group among them has not been reported. Therefore, The aim of this study was to uncover (I) gymnastic equipment is there potential pathogenic factors and (ii) is there any difference in the biomarker of bacterial in different types of gymnastic room? The samples were collected from the gymnastics halls of one university in western China and main sports equipment, including gymnastics carpets, moving barres, hoops and balls, as well as wall bars, parallel bars and horizontal bars. The 16S rDNA of all the samples was sequenced, and the analyses were performed using FaproTax, Bug base function prediction and Line Discriminant Analysis (LDA) Effect Size. A 16S rDNA sequence analysis revealed abundant bacterial species biodiversity on gymnasts and apparatuses from two gymnastics halls at a university in western China. An analysis using the FaproTax and Bugbase functional prediction platforms showed that there were some opportunistic pathogens on the athletes and equipment from the Rhythmic Gymnastics (RG) and Artistic Gymnastics (AG) halls, such as Staphylococcus and Corynebacteiaceae. Infectious agents associated with cancer induction and development, such as Ruminococcaceae, Veillonellaceae and Moraxellaceae, as well as microbial toxin producers with a potential impact on human health, were also detected. According to a line discriminant analysis (LDA effect size), the bacterial biomarker groups of the two gymnasiums were different at the phylum-genus level: for RG, Erysipelatoclostridium, Lachnospiraceae and Bacteroidales, while for AG, Rhizobiales. Based on the results of the investigation, we suggest that more comprehensive consideration should be given to indoor microbial biodiversity and related public health problems in school gymnasiums.
The precise measurement of the spectrum of protons, the most abundant component of the cosmic radiation, is necessary to understand the source and acceleration of cosmic rays in the Milky Way. This ...work reports the measurement of the cosmic ray proton fluxes with kinetic energies from 40 GeV to 100 TeV, with 2
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years of data recorded by the DArk Matter Particle Explorer (DAMPE). This is the first time that an experiment directly measures the cosmic ray protons up to ~100 TeV with high statistics. The measured spectrum confirms the spectral hardening at ~300 GeV found by previous experiments and reveals a softening at ~13.6 TeV, with the spectral index changing from ~2.60 to ~2.85. Our result suggests the existence of a new spectral feature of cosmic rays at energies lower than the so-called knee and sheds new light on the origin of Galactic cosmic rays.
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation ...technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
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