Small RNA Profiles of Serum Exosomes Derived From Individuals With Latent and Active Tuberculosis

Tuberculosis (TB) has been the leading lethal infectious disease worldwide since 2014, and about one third of the world’s population has a latent TB infection (LTBI). This is largely attributed to the difficulties in diagnosis and treatment of TB and LTBI patients. Exosomes offer a new perspective on investigation of the process of TB infection. In this study, we performed small RNA sequencing to explore small RNA profiles of serum exosomes derived from LTBI and TB patients and healthy controls (HC). Our results revealed distinct miRNA profile of the exosomes in the three groups. We screened 250 differentially expressed miRNAs including 130 specifically expressed miRNAs. Some miRNAs were further validated to be specifically expressed in LTBI (hsa-let-7e-5p, hsa-let-7d-5p, hsa-miR-450a-5p, and hsa-miR-140-5p) and TB samples (hsa-miR-1246, hsa-miR-2110, hsa-miR-370-3P, hsa-miR-28-3p, and hsa-miR-193b-5p). Additionally, we demonstrated four expression panels in LTBI and TB groups, and six expression patterns among the three groups. These specifically expressed miRNAs and differentially expressed miRNAs in different panels and patterns provide potential biomarkers for detection/diagnosis of latent and active TB using exosomal miRNAs. Additionally, we also discovered plenty of small RNAs derived from genomic repetitive sequences, which might play roles in host immune responses along with Mtb infection progresses. Overall, our findings provide important reference and an improved understanding about miRNAs and repetitive region-derived small RNAs in exosomes during the Mtb infectious process, and facilitate the development of potential molecular targets for detection/diagnosis of latent and active tuberculosis

Advances on Driver Oncogenes of Lung Adenocarcinoma

The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as “driver oncogenes” responsible for both the initiation and maintenance of the malignancy. So far, 50% of lung adenocarcinoma has been found harbouring driver oncogenes, in which epidermal growth factor receptor pathway plays important roles. In this review, we will report mainly the advances on significance of some latest driver mutations

Clinical Application of Plasma miR-34b-3p and miR-302a-5p in the Diagnosis of Non-small Cell Lung Cancer

Background and objective MicroRNA is a kind of single-stranded non-coding RNA whose length is about 22 nucleotides and its abnormal expression is related to disease closely. This study is aiming to explore the relative expression of miR-34b-3p and miR-302a-5p in the plasma of non-small cell lung cancer (NSCLC) patients and its clinical value. Methods The levels of miR-34b-3p and miR-302a-5p in plasma were detected by real-time polymerase chain reaction (RT-PCR) in 86 patients with NSCLC, 64 patients with pulmonary tuberculosis (PTB) and 39 healthy subjects. Analyze their value in diagnosing NSCLC by contrasting and combining carcino-embryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragments 21-1 (CYFRA21-1). Results The levels of plasma miR-34b-3p and miR-302a-5p in NSCLC group were significantly higher than those in the PTB group and the healthy group (P<0.05). In patients with NSCLC, the levels of plasma miR-34b-3p was correlated with the diameter of tumor (P<0.01). When using one plasma marker to diagnose NSCLC, miR-302a-5p had the highest sensitivity (82.6%) and CEA had the highest specificity (81.6%). While combined two plasma markers, miR-34b-3p+miR-302a-5p had the highest sensitivity (80.2%) and miR-34b-3p+CEA had the highest specificity (81.4%). As detected multiple markers, miR-302a-5p+NSE+CYFRA21-1 had the highest sensitivity (81.4%) and miR-34b-3p+CEA+NSE had the highest specificity (90.3%). The combination of miR-34b-3p, miR-302a-5p and CEA obtained the highest area under the curve (AUC), which was 0.832. Logistic regression model indicated that miR-34b-3p was independent risk factor for NSCLC compared to control groups. Conclusion Plasma miR-34b-3p and miR-302a-5p could be used as biological markers for the diagnosis of NSCLC

Expression and clinical significance of aminopeptidase N/CD13 in non-small cell lung cancer

Background: The objective of this study was to analyze the expression of aminopeptidase N/CD13 (APN/CD13) in non-small cell lung cancer (NSCLC) and investigate its correlation with various clinical factors, including prognosis and efficacy of adjuvant chemotherapy. Materials and Methods: Using immunohistochemistry analysis, we analyzed the expression of CD13 in clinicopathologically characterized 127 NSCLC cases. The relationship between the expression levels of CD13 and clinical features was analyzed and presented. Statistical Analysis: The data were analyzed using statistical package for the social sciences software (Ver 13.0, IBM, USA). Those conforming to Gauss distribution criteria was represented as Mean ΁ SD and those not conforming to Gauss distribution criteria was represented as median (M). The overall survival was recorded from the date of surgery to the date of cancer-specific death. APN/CD13 expression levels and clinicopathological factors were analyzed by Chi-square test or by Fisher′s exact test. The Kaplan-Meier method was used to evaluate the probability of survival data and analyzed by Log rank test. Multivariate analysis was performed by Cox regression model. P < 0.05 was considered to be statistically significant. Results: APN/CD13 was mainly expressed in the cellular membrane of cancer cells in pulmonary adenocarcinoma and in the cellular membrane of interstitial cells in squamous carcinoma. Positive APN/CD13 was detected in 62.3% (43 of 69) squamous carcinoma patients and in 50% (29/58) adenocarcinoma patients. Expression of APN/CD13 was not correlated with age, gender, tumor, node, metastasis (TNM) stage, histological type and tumor size, but with TNM stage (P = 0.041) and lymph node metastasis status (P = 0.009). As indicated by Kaplan-Meier survival curve, over-expression of APN/CD13 was significantly correlated with the low survival rate. Cox regression analysis showed that APN/CD13 expression was an independent impact factor for the survival of lung adenocarcinoma patients receiving adjuvant chemotherapy (P = 0.006). Conclusions: Expression of APN/CD13 is a potential unfavorable factor to predict the efficacy and prognosis of post-operative chemotherapy in NSCLC patients, especially in lung adenocarcinoma patients

Influence of the Eccentric Error of Star Gear on the Bifurcation Properties of Herringbone Star Gear Transmission with Floating Sun Gear

Taking a herringbone star gear transmission (HSGT) with floating sun gear as an example, the system bifurcation characteristics with the changing of the eccentric error of star gear and the working frequencies are analyzed. For this analysis, a generalized dynamic model of HSGT considering the manufacturing eccentric errors, time-varying mesh stiffness, and load balancing mechanism is established and solved by numerical method. The floating process of sun gear is explained. In this paper, there are seven cases about the eccentric errors of star gears which are calculated, respectively. To study the effect of the working frequencies (including meshing frequency and rotation frequency), the calculation is done at three kinds of input speed in which the working frequencies are close to the system natural frequencies. The results are demonstrated in detail by the bifurcation diagrams, phase plane plots, and Poincare maps. The system bifurcation characteristics are particularly analyzed and compared in every case. This work provides important guidance to the engineering of HSGT

Mutations Found in embCAB, embR, and ubiA Genes of Ethambutol-Sensitive and -Resistant Mycobacterium tuberculosis Clinical Isolates from China

To better understand the molecular mechanisms of Ethambutol (EMB) resistance, the mutant hot spot region of five genes (embB, embA, embC, embR, and ubiA) was amplified and sequenced in 109 EMB-resistant and 153 EMB-susceptible clinical isolates from China. Twenty-seven EMB-susceptible isolates were found to have nonsynonym mutations, 23 of which were in embB. The mutations occurred most frequently in embB (85.3%, 93) and were seldom in embC (2.8%, 3), embA (3.7%, 4), embR (3.7%, 4), and ubiA (8.3%, 9) in EMB-resistant isolates. For the embB gene, 63 isolates showed mutations at embB306, 20 at embB406, nine at embB497, and five at embB354 in EMB-resistant isolates. In addition, the particular mutants at embB406 and embB497 indicated both high levels of EMB resistance (MICs>5 μg/mL) and broad anti-TB drug resistance spectrums. Our data supported the facts that embB306 could be used as a marker for EMB resistance with a sensitivity of 57.8% and a specificity of 78.8%

Evaluation of the Roles of Four Candida albicans Genes in Virulence by Using Gene Disruption Strains That Express URA3 from the Native Locus

Reintroducing URA3 to its native locus in Candida albicans not5, not3, bur2, and kel1 disruption mutants enabled us to directly compare strains with control strain CAI-12. We showed that URA3 position affected orotidine 5′-monophosphate decarboxylase activity, hyphal morphogenesis, adherence, and mortality in murine disseminated candidiasis. After URA3 was reintroduced to its native locus, only NOT5 could be conclusively ascribed a role in virulence

Chemical Ordering induced Strengthening in Lightweight Mg Alloys

The influence of structure and composition on precipitation phenomena in Al-bearing BCC/HCP Mg alloys are studied via diffusion couple technique. Interdiffusion induced by the resultant composition gradient results in a change in crystal structure from HCP to BCC in the diffusion zone. The Vickers hardness in the diffusion zone is much higher than that in the Mg–5.5at.%Al and Mg–38at.%Li, which is attributed to the chemical ordering by nano-sized secondary ordered D03–Mg3Al precipitation in the BCC Mg–Li–Al diffusion zone. The reasons for different precipitation in Al-bearing Mg alloys with various matrices are discussed. Generating ordered precipitates can be an effective approach to improve both strength and ductility in HCP Mg alloys

Chemical Variation and Environmental Influence on Essential Oil of <i>Cinnamomum camphora</i>

Cinnamomum camphora is a traditional aromatic plant used to produce linalool and borneol flavors in southern China; however, its leaves also contain many other unutilized essential oils. Herein, we report geographic relationships for the yield and compositional diversity of C. camphora essential oils. The essential oils of 974 individual trees from 35 populations in 13 provinces were extracted by hydrodistillation and analyzed qualitatively and quantitatively by gas chromatography-mass spectrometry and gas chromatography-flame ionization detection, respectively. Oil yields ranged from 0.01% to 3.46%, with a significantly positive correlation with latitude and a significantly negative correlation with longitude. In total, 41 compounds were identified, including 15 monoterpenoids, 24 sesquiterpenoids, and two phenylpropanoids. Essential oil compositions varied significantly among individuals and could be categorized into various chemotypes. The six main chemotypes were eucalyptol, nerolidol, camphor, linalool, selina, and mixed types. The other 17 individual plants were chemotypically rare and exhibited high levels of methyl isoeugenol, methyl eugenol, δ-selinene, or borneol. Eucalyptol-type plants had the highest average oil yield of 1.64%, followed in decreasing order by linalool-, camphor-, mixed-, selina-, and nerolidol-type plants. In addition, the five main compounds exhibited a clear geographic gradient. Eucalyptol and linalool showed a significantly positive correlation with latitude, while selina-6-en-4-ol was significantly and negatively correlated with latitude. trans-Nerolidol and selina-6-en-4-ol showed significantly positive correlations with longitude, whereas camphor was significantly and negatively correlated with longitude. Canonical correspondence analysis indicated that environmental factors could strong effect the oil yield and essential oil profile of C. camphora

Interferon-Gamma Release Assay Performance of Cerebrospinal Fluid and Peripheral Blood in Tuberculous Meningitis in China

The aim of this study was to examine the performance of T-SPOT.TB on cerebrospinal fluid (CSF) and peripheral blood (PB) in diagnosis of tuberculous meningitis (TBM) in China. Of 100 patients with presumed TBM prospectively enrolled from Sep 2012 to Oct 2014, 53 were TBM (21 definite and 32 probable TBM cases) and 37 were non-TBM cases; the other 10 patients were excluded from analysis due to inconclusive diagnosis, no sufficient CSF samples, or incomplete follow-up. T-SPOT.TB on CSF and PB and routine laboratory tests of CSF were performed simultaneously. The receiver operating characteristic (ROC) curve and cut-off value of CSF T-SPOT.TB and routine CSF parameters were established between TBM and non-TBM group. The area under ROC curve (AUC) of the T-SPOT.TB on CSF and PB was 0.81 and 0.89, which was higher than that of the routine CSF parameters (AUC 0.67–0.77). Although the sensitivity of CSF T-SPOT.TB was lower than that of PB T-SPOT.TB (60.8% versus 90.6%, P<0.001), the specificity of CSF T-SPOT.TB was significantly higher than that of PB T-SPOT.TB (97.2% versus 75.7%, P=0.007). These results indicated that the diagnostic accuracies of PB and CSF T-SPOT.TB are higher than routine laboratory tests. Furthermore, the higher specificity of CSF T-SPOT.TB makes it a useful rule-in test in rapid diagnosis of TBM