A facile and efficient single-step approach for the fabrication of vancomycin functionalized polymer-based monolith as chiral stationary phase for nano-liquid chromatography

A facile single-step preparation strategy for fabricating vancomycin functionalized organic polymer based monolith within 100 mu m fused-silica capillary was developed. The synthetic chiral functional monomer, i.e 2-isocyanatoethyl methacrylate (ICNEML) derivative of vancomycin, was co-polymerized with the cross-linker ethylene dimethacrylate (EDMA) in the presence of methanol and dimethyl sulfoxide as the selected porogens. The co-polymerization conditions were systematically optimized in order to obtain satisfactory column performance. Adequate permeability, stability and column morphology were observed for the optimized poly(ICNEML-vancomycin-co-EDMA) monolith. A series of chiral drugs were evaluated on the monolith in either several other beta-blockers. The proposed single-step approach not only resulted in a vancomycin functionalized organer polar organic-phase or reversed-phase modes. After the optimization of separation conditions, baseline or partial enantioseparation were obtained for series of drugs including thalidomide, colchicine, carteolol, salbutamol, clenbuterol andic polymer-based monolith with acceptable performance, but also significantly simplified the preparation procedure by reducing time and labor

Identification of the Signature Associated With m6A RNA Methylation Regulators and m6A-Related Genes and Construction of the Risk Score for Prognostication in Early-Stage Lung Adenocarcinoma

BackgroundN6-methyladenosine (m6A) RNA modification is vital for cancers because methylation can alter gene expression and even affect some functional modification. Our study aimed to analyze m6A RNA methylation regulators and m6A-related genes to understand the prognosis of early lung adenocarcinoma.MethodsThe relevant datasets were utilized to analyze 21 m6A RNA methylation regulators and 5,486 m6A-related genes in m6Avar. Univariate Cox regression analysis, random survival forest analysis, Kaplan–Meier analysis, Chi-square analysis, and multivariate cox analysis were carried out on the datasets, and a risk prognostic model based on three feature genes was constructed.ResultsRespectively, we treated GSE31210 (n = 226) as the training set, GSE50081 (n = 128) and TCGA data (n = 400) as the test set. By performing univariable cox regression analysis and random survival forest algorithm in the training group, 218 genes were significant and three prognosis-related genes (ZCRB1, ADH1C, and YTHDC2) were screened out, which could divide LUAD patients into low and high-risk group (P < 0.0001). The predictive efficacy of the model was confirmed in the test group GSE50081 (P = 0.0018) and the TCGA datasets (P = 0.014). Multivariable cox manifested that the three-gene signature was an independent risk factor in LUAD. Furthermore, genes in the signature were also externally validated using the online database. Moreover, YTHDC2 was the important gene in the risk score model and played a vital role in readers of m6A methylation.ConclusionThe findings of this study suggested that associated with m6A RNA methylation regulators and m6A-related genes, the three-gene signature was a reliable prognostic indicator for LUAD patients, indicating a clinical application prospect to serve as a potential therapeutic target

A Highway In-Transit Vehicle Position Estimation Method Considering Road Characteristics and Short-Term Driving Style

Existing vehicle position estimation methods are mostly based on Global Positioning System (GPS) or a fusion of GPS and machine learning methods to realize vehicle position estimation. While highway tunnels are many, GPS signals are easy to be interfered, and the vehicle loading rate of GPS devices is limited, this kind of method can not be realized in a wide range of applications. In this context, taking into account the ETC equipment that has been deployed and applied in large scale in China, the vehicle equipment loading rate is over 90%, but the ETC gantry interval is large, and it is not possible to effectively perceive the vehicle driving status inside the segment. Therefore, this paper is based on the ETC transaction data to build the basic driving characteristics and short-term driving style of the vehicle history segment, using GPS positioning data to build the internal characteristics of the segment, including the characteristics of the road structure within the segment, the pattern of change of the vehicle position, so as to put forward the highway in-transit vehicle position estimation method that considers the road characteristics and short-term driving style. Firstly, the SC-Kmeans-Bilstm vehicle segment speed prediction model based on PCA optimization is constructed by fusing vehicle short-term driving styles; secondly, the road model within the segment is constructed by using moving average and wavelet smoothing methods; lastly, the vehicle position data is temporally stabilized using linear interpolation and first-order inverse difference, and vehicle position estimation within the highway segment is realized by using DLCNN-LSTM-ATTENTION fusion model based on L1 regularization by combining vehicle segment speeds, road characteristics, and vehicle base driving characteristics. Among them, the short-term driving style helps us to obtain the vehicle segment speed more accurately, and the addition of the road model makes this method better explain the variability of the data. The experimental results show that the present method can achieve on- travel vehicle position estimation within 2km with an error of less than 50m in a full-sample highway environment, and can provide over-the-horizon sensing for intelligent vehicles

Expression from DIF1-motif promoters of hetR and patS is dependent on HetZ and modulated by PatU3 during heterocyst differentiation

HetR and PatS/PatX-derived peptides are the activator and diffusible inhibitor for cell differentiation and patterning in heterocyst-forming cyanobacteria. HetR regulates target genes via HetR-recognition sites. However, some genes (such as patS/patX) upregulated at the early stage of heterocyst differentiation possess DIF1 (or DIF+) motif (TCCGGA) promoters rather than HetR-recognition sites; hetR possesses both predicted regulatory elements. How HetR controls heterocyst-specific expression from DIF1 motif promoters remains to be answered. This study presents evidence that the expression from DIF1 motif promoters of hetR, patS and patX is more directly dependent on hetZ, a gene regulated by HetR via a HetR-recognition site. The HetR-binding site upstream of hetR is not required for the autoregulation of hetR. PatU3 (3' portion of PatU) that interacts with HetZ may modulate the expression of hetR, hetZ and patS. These findings contribute to understanding of the mutual regulation of hetR, hetZ-patU and patS/patX in a large group of multicellular cyanobacteria

Correction: Expression from DIF1-motif promoters of hetR and patS is dependent on HetZ and modulated by PatU3 during heterocyst differentiation.

[This corrects the article DOI: 10.1371/journal.pone.0232383.]

Infection and Colonization of Pathogenic Fungus Fusarium proliferatum in Rice Spikelet Rot Disease

Rice spikelet rot disease (RSRD), caused by Fusarium proliferatum, is an emerging disease. So far, the effects of diseased rice floral organs as well as the primary infection sites and stages of this pathogen are not determined. We investigated changes in the floral organs, along with the infection processes of the pathogen in plants inoculated with F. proliferatum and labelled with a green fluorescent protein during different growth stages of rice. The results showed that RSRD is not a systemic infectious disease, which has negative effects on the fertility of the infected rice. F. proliferatum caused brown colored anthers, crinkled pistils and ovaries, pollen grain deformities and anther indehiscence. The number of pollen grains on the stigmas decreased significantly in the infected spikelets, and the anther dehiscence and seed-setting rate successively declined by 69% and 73%, respectively, as a result of the infection. The initial infection stage occurred at the pollen cell maturity stage, and the primary invasion sites were determined to be the anthers of rice. It was noted that the pathogen mainly damaged the pollen cells, and with the exception of the filaments, proceeded to colonize the pistils and endosperm. Keywords: Fusarium proliferatum, rice spikelet rot disease, green fluorescent protein, infection process, infection stage, invasion sit

MicroRNA-29a-3p prevents Schistosoma japonicum-induced liver fibrosis by targeting Roundabout homolog 1 in hepatic stellate cells

Abstract Background Schistosomiasis is a serious but neglected parasitic disease in humans that may lead to liver fibrosis and death. Activated hepatic stellate cells (HSCs) are the principal effectors that promote the accumulation of extracellular matrix (ECM) proteins during hepatic fibrosis. Aberrant microRNA-29 expression is involved in the development of fibrotic diseases. However, less is known about the role of miR-29 in Schistosoma japonicum (S. japonicum)-induced hepatic fibrosis. Methods The levels of microRNA-29a-3p (miR-29a-3p) and Roundabout homolog 1 (Robo1) were examined in liver tissues during S. japonicum infection. The possible involvement of the miR-29a-3p-Robo1 signaling pathway was determined. We used MIR29A conditional knock-in mice and mice injected with an miR-29a-3p agomir to investigate the role of miR-29a-3p in schistosomiasis-induced hepatic fibrosis. The functional contributions of miR-29a-3p-Robo1 signaling in liver fibrosis and HSC activation were investigated using primary mouse HSCs and the human HSC cell line LX-2. Results MiR-29a-3p was downregulated in humans and mice with schistosome-induced fibrosis, and Robo1 was upregulated in liver tissues. The miR-29a-3p targeted Robo1 and negatively regulated its expression. Additionally, the expression level of miR-29a-3p in schistosomiasis patients was highly correlated with the portal vein and spleen thickness diameter, which represent the severity of fibrosis. Furthermore, we demonstrated that efficient and sustained elevation of miR-29a-3p reversed schistosome-induced hepatic fibrosis. Notably, we showed that miR-29a-3p targeted Robo1 in HSCs to prevent the activation of HSCs during infection. Conclusions Our results provide experimental and clinical evidence that the miR-29a-3p-Robo1 signaling pathway in HSCs plays an important role in the development of hepatic fibrosis. Therefore, our study highlights the potential of miR-29a-3p as a therapeutic intervention for schistosomiasis and other fibrotic diseases. Graphical Abstrac