Lung cancer is the most commonly diagnosed cancer worldwide, and metastasis in lung cancer is the leading cause of cancer‐related deaths. Thus, understanding the mechanism of lung cancer metastasis ...will improve the diagnosis and treatment of lung cancer patients. Herein, we found that expression of cluster of differentiation 109 (CD109) was correlated with the invasive and metastatic capacities of lung adenocarcinoma cells. CD109 is upregulated in tumorous tissues, and CD109 overexpression was associated with tumor progression, distant metastasis, and a poor prognosis in patient with lung adenocarcinoma. Mechanistically, expression of CD109 regulates protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling via its association with the epidermal growth factor receptor (EGFR). Inhibition of CD109 decreases EGFR phosphorylation, diminishes EGF‐elicited activation of AKT/mTOR, and sensitizes tumor cells to an EGFR inhibitor. Taken together, our results show that CD109 is a potential diagnostic and therapeutic target in lung cancer patients.
CD109 promotes lung cancer metastasis through promoting EGFR‐AKT‐mTOR signaling and CD109 is an independent prognostic marker for lung adenocarcinoma.
Dysbiosis of the gut microbiome is associated with host health conditions. Many diseases have shown to have correlations with imbalanced microbiota, including obesity, inflammatory bowel disease, ...cancer, and even neurodegeneration disorders. Metabolomics studies targeting small molecule metabolites that impact the host metabolome and their biochemical functions have shown promise for studying host-gut microbiota interactions. Metabolome analysis determines the metabolites being discussed for their biological implications in host-gut microbiota interactions. To facilitate understanding the critical aspects of metabolome analysis, this article reviewed (1) the sample types used in host-gut microbiome studies; (2) mass spectrometry (MS)-based analytical methods and (3) useful tools for MS-based data processing/analysis. In addition to the most frequently used sample type, feces, we also discussed others biosamples, such as urine, plasma/serum, saliva, cerebrospinal fluid, exhaled breaths, and tissues, to better understand gut metabolite systemic effects on the whole organism. Gas chromatography-mass spectrometry (GC–MS), liquid chromatography-mass spectrometry (LC-MS), and capillary electrophoresis-mass spectrometry (CE-MS), three powerful tools that can be utilized to study host-gut microbiota interactions, are included with examples of their applications. After obtaining big data from MS-based instruments, noise removal, peak detection, missing value imputation, and data analysis are all important steps for acquiring valid results in host-gut microbiome research. The information provided in this review will help new researchers aiming to join this field by providing a global view of the analytical aspects involved in gut microbiota-related metabolomics studies.
Macrophages play essential roles throughout the wound repair process. Nevertheless, mechanisms regulating the process are poorly understood. MAFB is specifically expressed in the macrophages in ...hematopoietic tissue and is vital to homeostatic function. Comparison of the skin wound repair rates in macrophage-specific, MAFB-deficient mice (Mafbf/f::LysM-Cre) and control mice (Mafbf/f) showed that wound healing was significantly delayed in the former. For wounded GFP knock-in mice with GFP inserts in the Mafb locus, flow cytometry revealed that their GFP-positive cells expressed macrophage markers. Thus, macrophages express Mafb at wound sites. Immunohistochemical (IHC) staining, proteome analysis, and RT-qPCR of the wound tissue showed relative downregulation of Arg1, Ccl12, and Ccl2 in Mafbf/f::LysM-Cre mice. The aforementioned genes were also downregulated in the bone marrow-derived, M2-type macrophages of Mafbf/f::LysM-Cre mice. Published single-cell RNA-Seq analyses showed that Arg1, Ccl2, Ccl12, and Il-10 were expressed in distinct populations of MAFB-expressing cells. Hence, the MAFB-expressing macrophage population is heterogeneous. MAFB plays the vital role of regulating multiple genes implicated in wound healing, which suggests that MAFB is a potential therapeutic target in wound healing.
Colorectal cancer (CRC) is currently the third leading cause of cancer-related mortality in the world. U.S. Food and Drug Administration-approved circulating tumor markers, including carcinoembryonic ...antigen, carbohydrate antigen (CA) 19-9 and CA125 were used as prognostic biomarkers of CRC that attributed to low sensitivity in diagnosis of CRC. Therefore, our purpose is to develop a novel strategy for novel clinical biomarkers for early CRC diagnosis. We used mass spectrometry (MS) methods such as nanoLC-MS/MS, targeted LC-MS/MS, and stable isotope-labeled multiple reaction monitoring (MRM) MS coupled to test machine learning algorithms and logistic regression to analyze plasma samples from patients with early-stage CRC, late-stage CRC, and healthy controls (HCs). On the basis of our methods, 356 peptides were identified, 6 differential expressed peptides were verified, and finally three peptides corresponding wheat germ agglutinin (WGA)-captured proteins were semi-quantitated in 286 plasma samples (80 HCs and 206 CRCs). The novel peptide biomarkers combination of PF454–62, ITIH4429–438, and APOE198–207 achieved sensitivity 84.5%, specificity 97.5% and an AUC of 0.96 in CRC diagnosis. In conclusion, our study demonstrated that WGA-captured plasma PF454–62, ITIH4429–438, and APOE198–207 levels in combination may serve as highly effective early diagnostic biomarkers for patients with CRC.
In this article, we present a new architecture for the Internet of Vehicles (IoVs) that feature reduced system complexity and enhanced radio‐frequency (RF) performance. The proposed system requires ...no complex coding or selection algorithms, yet it significantly improves the received signal strength. We implement dual‐port antennas comprising a linearly polarized (LP) antenna and a circularly polarized (CP) antenna, which minimize the polarization loss between multipath signals and the receiving antenna. Using Wi‐Fi communications, we designed, fabricated, and examined a prototype system comprising seven circuit modules that employ spatial diversity and revised polarization diversity simultaneously. We test its performance using two antenna combinations with distinct peak gain characteristics. Our results show these antennas have highly desirable impedance matching and radiation properties and enhanced received signal strength compared to conventional techniques. As such, the proposed system can greatly improve signal quality and reliability in non‐line‐of‐sight (NLOS) IoV scenarios.
: Cancer cells reprogram cellular metabolism to fulfill their needs for rapid growth and metastasis. However, the mechanism controlling this reprogramming is poorly understood. We searched for ...upregulated signaling in metastatic colorectal cancer and investigated the mechanism by which Glut3 promotes tumor metastasis.
: We compared RNA levels and glycolytic capacity in primary and metastatic colon cancer. The expression and association of Glut3 with clinical prognosis in colon cancer tissues was determined by immunohistochemistry. Glut3 gain-of-function and loss-of-function were established using colon cancer HCT116, HT29, and metastatic 116-LM cells, and tumor invasiveness and stemness properties were evaluated. Metabolomic profiles were analyzed by GC/MS and CE-TOF/MS. The metastatic burden in mice fed a high-fat sucrose diet was assessed by intravenous inoculation with Glut3 knockdown 116-LM cells.
: Upregulation of glycolytic genes and glycolytic capacity was detected in metastatic colorectal cancer cells. Specifically, Glut3 overexpression was associated with metastasis and poor survival in colorectal cancer patients. Mechanistically, Glut3 promoted invasiveness and stemness in a Yes-associated protein (YAP)-dependent manner. Activation of YAP in turn transactivated Glut3 and regulated a group of glycolytic genes. Interestingly, the expression and phosphorylation of PKM2 were concomitantly upregulated in metastatic colorectal cancer, and it was found to interact with YAP and enhance the expression of Glut3. Importantly, a high-fat high-sucrose diet promoted tumor metastasis, whereas the inhibition of either Glut3 or YAP effectively reduced the metastatic burden.
: Activation of the Glut3-YAP signaling pathway acts as a master activator to reprogram cancer metabolism and thereby promotes metastasis. Our findings reveal the importance of metabolic reprogramming in supporting cancer metastasis as well as possible therapeutic targets.
Antibiotic-resistant bacterial infection is one of the most serious clinical problems worldwide. Vancomycin, teicoplanin, daptomycin, and colistin are glycopeptide and lipopeptide antibiotics that ...are frequently used to treat multidrug-resistant bacterial infections. Therapeutic drug monitoring is recommended to ensure both safety and efficacy and to improve clinical outcomes. This study developed a fast, simple, and sensitive ultra-high-pressure liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method for the simultaneous determination of the concentrations of these four drugs in human plasma. The sample preparation process includes a simple protein denaturation step using acetonitrile, followed by an 11-fold dilution with 0.1% formic acid. Eight target peaks for the four drugs can be analyzed within 3min using a Kinetex™ 2.6μm C18 column. The mass spectrometry parameters were optimized, and two transitions for each target peak were used for multiple reaction monitoring, which provided high sensitivity and specificity. The UHPLC–MS/MS method was validated over clinical concentration ranges. The intra-day and inter-day precisions for the ratio of the peak area of each analyte to the peak area of the internal standard were all below 12.7 and 14.7% relative standard deviations, respectively. The accuracy at low, medium, and high concentrations of the eight target peaks was between 89.3 and 110.7%. The standard curves for the analytes were linear and had coefficients of determination higher than 0.997. The limits of detection were all below 70ngmL−1. The use of this method to analyze patient plasma samples confirmed that it is effective for the therapeutic drug monitoring of these four drugs and can be used to improve the therapeutic efficacy and safety of treatment with antibiotics.
•Efficient LC–MS/MS method was developed for determination of antimicrobial agents.•Vancomycin, teicoplanin, daptomycin, and colistin can be quantified simultaneously.•The developed LC–MS method can detect all six sub-components of teicoplanin.•Sample preparation is simple with protein precipitation and an 11-fold dilution.•The method was successfully applied to patients’ plasma for drug quantification.
In this paper, we propose a novel technique that integrates the detection of element failures and the correction of damaged patterns into a systematic process for active phased arrays. The proposed ...technique uses the framework of mutual coupling method, and its kernel is based on a cumulative sum (CUSUM) scheme that monitors attenuators and phase shifters inside transmit/receive modules. The proposed method is organized into two phases. The phase one copes with the detection of failed components. By cumulating time-series data, the CUSUM can readily detect the defective elements even though very small shifts are examined. We test the effectiveness through a 448-element active phased array. The measured results show that no type I error is found, and the type II error of the most challenging scenario is significantly reduced. The phase two aims at the correction of patterns. By integrating the experimental result provided by the phase one and a least-squares method, the proposed technique can determine the new excitations leading to reduced sidelobe levels and a desired main beam characteristic. The capability is verified through three examples including linear and planar arrays. The results show that the proposed method can correct the damaged patterns with low computational complexity.
Type 1 autoimmune pancreatitis (AIP) is categorized as an IgG4-related disease (IgG4-RD), where a high concentration of plasma IgG4 is one of the common biomarkers among patients. IgG ...Fc-glycosylation has been reported to be potential biosignatures for diseases. However, human IgG3 and IgG4 Fc-glycopeptides from populations in Asia were found to be isobaric ions when using LC-MS/MS as an analytical tool. In this study, an analytical workflow that coupled affinity purification and stable isotope dilution LC-MS/MS was developed to dissect IgG4 glycosylation profiles for autoimmune pancreatitis. Comparing the IgG4 and glycosylation profiles among healthy controls, patients with pancreatic ductal adenocarcinoma (PDAC), and AIP, the IgG4 glycosylations from the AIP group were found to have more digalactosylation (compared to PDAC) and less monogalactosylation (compared to HC). In addition, higher fucosylation and sialylation profiles were also discovered for the AIP group. The workflow is efficient and selective for IgG4 glycopeptides, and can be used for clinical biosignature discovery.
Although high-affinity immunoglobulin (Ig)E receptor (FcεRI) expression is upregulated in type 2 (T2)-high asthmatic airway epithelium, its functional role in airway epithelial dysfunction has not ...been elucidated. Here we report the upregulated expression of FcεRI and p-EGFR (Epidermal Growth Factor Receptor), associated with decreased expression of E-cadherin and claudin-18 in bronchial biopsies of severe T2-high asthmatics compared to mild allergic asthmatics and non-T2 asthmatics. Monomeric IgE (mIgE) decreased the expression of junction proteins, E-cadherin, claudin-18, and ZO-1, and increased alarmin messenger RNA and protein expression in cultured primary bronchial epithelial cells from T2-high asthmatics. Epithelial FcεRI ligation with mIgE decreased transepithelial electric resistance in air-liquid interface cultured epithelial cells. FcεRI ligation with mIgE or IgE- Dinitrophenyl or serum of high-level allergen-specific IgE activated EGFR and Akt via activation of Src family kinases, mediating alarmin expression, junctional protein loss, and increased epithelial permeability. Furthermore, tracheal instillation of mIgE in house dust mite-sensitized mice induced airway hyper-responsiveness, junction protein loss, epithelial cell shedding, and increased epithelial permeability. Thus, our results suggest that IgE-FcεRI cross-linking in the airway epithelium is a potential and unnoticed mechanism for impaired barrier function, increased mucosal permeability, and EGFR-mediated alarmin production in T2-high asthma.
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