The emerging role of lncRNAs in osteoarthritis development and potential therapy

Osteoarthritis impairs the functions of various joints, such as knees, hips, hands and spine, which causes pain, swelling, stiffness and reduced mobility in joints. Multiple factors, including age, joint injuries, obesity, and mechanical stress, could contribute to osteoarthritis development and progression. Evidence has demonstrated that genetics and epigenetics play a critical role in osteoarthritis initiation and progression. Noncoding RNAs (ncRNAs) have been revealed to participate in osteoarthritis development. In this review, we describe the pivotal functions and molecular mechanisms of numerous lncRNAs in osteoarthritis progression. We mention that long noncoding RNAs (lncRNAs) could be biomarkers for osteoarthritis diagnosis, prognosis and therapeutic targets. Moreover, we highlight the several compounds that alleviate osteoarthritis progression in part via targeting lncRNAs. Furthermore, we provide the future perspectives regarding the potential application of lncRNAs in diagnosis, treatment and prognosis of osteoarthritis

Conversion of saccharides into levulinic acid and 5-hydroxymethylfurfural over WO3-Ta2O5 catalysts

Bimetallic oxide catalysts WO3-Ta2O5 are active in converting saccharides into 5-hydroxymethylfurfural (HMF) and levulinic acid (LA) in one-pot reactions. The product selectivity varies at different WO3 to Ta2O5 ratios. FTIR measurements indicate the presence of Lewis acid sites and the strength of the Lewis acid sites varies when the WO3 to Ta2O5 ratio changes. The result suggests that conversion of carbohydrates into HMF and LA can be realized using a single catalytic system by adjusting the catalyst's acidic properties

The inhibition of LPS-induced inflammation in RAW264.7 macrophages via the PI3K/Akt pathway by highly N-acetylated chitooligosaccharide

Chitooligosaccharide (COS) has been shown to regulate many biological functions, such as antimicrobial effect and antitumor activity. In the present study, highly N-acetylated chitooligosaccharide(NACOS) was prepared by N-acetylation of COS, and the anti-inflammatory activity of NACOS in macrophages were evaluated. The results indicated NACOS significantly suppressed the LPS-induced proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha(TNF-alpha) expression. Furthermore, the increased levels of reactive oxygen species (ROS) and nitric oxide (NO) were repressed by NACOS in a dose dependent manner. However, NACOS itself had no significant effect on the cell viability and cellular morphology. Signal transduction studies demonstrated that NACOS remarkably inhibited LPS-enhanced phosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt. These findings provide a possible molecular mechanism by which NACOS inhibit LPS-induced inflammatory response in macrophages, and a basis for utilizing NACOS in pharmaceutical therapy against inflammation. (C) 2017 Elsevier Ltd. All rights reserved.</p

Long non-coding RNA MALAT1 contributes to cell apoptosis by sponging miR-124 in Parkinson disease

Abstract Background Parkinson disease (PD) is the most common movement disturbance characterized by the loss of dopaminergic (DA) neurons in midbrain. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is aberrantly expressed in neurons and is involved in the dendritic and synapse development. However, the role of MALAT1 and its underlying mechanism in PD remain to be defined. Methods The expressions of MALAT1 and miR-124 were evaluated by qRT-PCR. N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and SH-SY5Y cells subjected to N-methyl-4-phenylpyridinium (MPP+) were utilized to investigate the effect of MALAT1 on PD. TUNEL assay was performed to detect apoptosis of DA neurons in PD mice. Flow cytometry analysis was carried out to measure apoptosis of SH-SY5Y cells. Caspase3 activity and Cleaved Caspase3 expression were tested by caspase3 assay kit and western blot, respectively. TargetScan software and luciferase reporter assay were used to explore the relationship between MALAT1 and miR-124. Results MALAT1 was up-regulated and miR-124 was down-regulated in MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. MALAT1 knockdown attenuated MPTP-induced apoptosis of DA neurons in MPTP-induced PD mouse model. MALAT1 interacted with miR-124 to negatively regulate its expression. MALAT1 knockdown suppressed MPP+-induced apoptosis in SH-SY5Y cells, while miR-124 downregulation abrogated this effect. Moreover, MALAT1 knockdown improved miR-124 expression in MPTP/MPP+ induced models of PD. Conclusions MALAT1 promotes the apoptosis by sponging miR-124 in mouse models of PD and in vitro model of PD, providing a potential theoretical foundation for the clinical application of MALAT1 against PD

A Regional Model for Predicting Tropospheric Delay and Weighted Mean Temperature in China Based on GRAPES_MESO Forecasting Products

Accurate tropospheric delay (TD) and weighted mean temperature (Tm) are important for Global Navigation Satellite System (GNSS) positioning and GNSS meteorology. For this purpose, plenty of empirical models have been built to provide estimates of TD and Tm. However, these models cannot resolve TD and Tm variations at synoptic timescales since they only model the average annual, semi-annual, and/or daily variations. As a result, the existed empirical models cannot perform well under extreme weather conditions. To address this limitation, we propose to estimate Zenith Hydrostatic Delay (ZHD), Zenith Wet Delay (ZWD), and Tm directly from the stratified numerical weather forecasting products of the mesoscale version of the Global/Regional Assimilation and PrEdiction System (GRAPES_MESO) of China. The GRAPES_MESO forecasting data has a temporal resolution of 3 h, which provides the opportunity to resolve the synoptic variation. However, it is found that the estimated ZWD and Tm exhibit apparent systematic deviation from in situ observation-based estimates, which is due to the inherent biases in the GRAPES_MESO data. To solve this problem, we propose to correct these biases using a linear model and a spherical cap harmonic model. The estimates after correction are termed as the “CTropGrid” products. When validated by the radiosonde data, the CTropGrid product has biases of 1.5 mm, −0.7 mm, and −0.1 K, and Root Mean Square (RMS) error of 8.9 mm, 20.2 mm, and 1.5 K for ZHD, ZWD, and Tm. Compared to the widely used GPT2w model, the CTropGrid products have improved the accuracies of ZHD, ZWD, and Tm by 11.9%, 55.6%, and 60.5% in terms of RMS. When validating the Zenith Tropospheric Delay (ZTD) products (the sum of ZHD and ZWD) using the IGS ZTD data, the CTropGrid ZTD has a bias of −0.7 mm and an RMS of 35.8 mm, which is 22.7% better than the GPT2w model in terms of RMS. Besides the accuracy improvements, the CTropGrid products well model the synoptic-scale variations of ZHD, ZWD, and Tm. Compared to the existing empirical models that only capture the tidal (seasonal and/or diurnal) variations, the CTropGrid products capture well the non-tidal variations of ZHD, ZWD, and Tm, which enhances the tropospheric delay corrections and GNSS water vapor monitoring at synoptic timescales. Therefore, the CTropGrid product is an important progress in GNSS positioning and GNSS meteorology

Nanotheranostic Trojan Horse for visualization and photo-immunotherapy of multidrug-resistant bacterial infection

Abstract Effective diagnosis and therapy for bacterial infections, especially those caused by multidrug-resistant (MDR) species, greatly challenge current antimicrobial stewardship. Monocytes, which can chemotactically migrate from the blood to infection site and elicit a robust infection infiltration, provide a golden opportunity for bacterial theranostics. Here, a nano-Trojan Horse was facilely engineered using mannose-functionalized manganese-eumelanin coordination nanoparticles (denoted as MP-MENP) for precise two-step localization and potent photothermal-immunotherapy of MDR bacterial infection. Taking advantage of the selective recognition between mannose and inflammation-associated monocytes, the MP-MENP could be passively piggybacked to infection site by circulating monocytes, and also actively target infiltrated monocytes that are already accumulated in infection microenvironment. Such dual-pronged targeting enabled an efficient imaging diagnosis of bacterial infection. Upon laser irradiation, the MP-MENP robustly produced local hyperemia to ablate bacteria, both extracellularly and intracellularly. Further combined with photothermal therapy-induced immunogenic cell death and MP-MENP-mediated macrophage reprogramming, the immunosuppressive infection microenvironment was significantly relieved, allowing an enhanced antibacterial immunity. Collectively, the proposed nanotheranostic Trojan Horse, which integrates dual-pronged targeting, precise imaging diagnosis, and high-performance photothermal immunotherapy, promises a new way for complete eradication of MDR bacterial infection

Microevolution of the mexT and lasR Reinforces the Bias of Quorum Sensing System in Laboratory Strains of Pseudomonas aeruginosa PAO1

The Pseudomonas aeruginosa strain PAO1 has routinely been used as a laboratory model for quorum sensing (QS). However, the microevolution of P. aeruginosa laboratory strains resulting in genetic and phenotypic variations have caused inconsistencies in QS research. To investigate the underlying causes of these variations, we analyzed 5 Pseudomonas aeruginosa PAO1 sublines from our laboratory using a combination of phenotypic characterization, high throughput genome sequencing, and bioinformatic analysis. The major phenotypic variations among the sublines spanned across the levels of QS signals and virulence factors such as pyocyanin and elastase. Furthermore, the sublines exhibited distinct variations in motility and biofilm formation. Most of the phenotypic variations were mapped to mutations in the lasR and mexT, which are key components of the QS circuit. By introducing these mutations in the subline PAO1-E, which is devoid of such mutations, we confirmed their influence on QS, virulence, motility, and biofilm formation. The findings further highlight a possible divergent regulatory mechanism between the LasR and MexT in the P. aeruginosa. The results of our study reveal the effects of microevolution on the reproducibility of most research data from QS studies and further highlight mexT as a key component of the QS circuit of P. aeruginosa

A further exploitation of the attenuated-total-reflection technique to measure the complex second hyperpolarizability for the quadratic electro-optic effect of a linear conjugated polymer

By using the technique of the attenuated total reflection, the complex second hyperpolarizability for the quadratic electro-optic effect of a linear conjugated polymer is determined at the wavelength of the absorption edge by employing the data measured from different guided wave resonance dips. The values and the signs of the real and imaginary parts of the second hyperpolarizability are simultaneously obtained without employing the Kramers-Kronig transformation