Establishing an RNA-associated interaction repository facilitates the system-level understanding of RNA functions. However, as these interactions are distributed throughout various resources, an essential prerequisite for effectively applying these data requires that they are deposited together and annotated with confidence scores. Hence, we have updated the RNA-associated interaction database RNAInter (RNA Interactome Database) to version 4.0, which is freely accessible at http://www.rnainter.org or http://www.rna-society.org/rnainter/. Compared with previous versions, the current RNAInter not only contains an enlarged data set, but also an updated confidence scoring system. The merits of this 4.0 version can be summarized in the following points: (i) a redefined confidence scoring system as achieved by integrating the trust of experimental evidence, the trust of the scientific community and the types of tissues/cells, (ii) a redesigned fully functional database that enables for a more rapid retrieval and browsing of interactions via an upgraded user-friendly interface and (iii) an update of entries to >47 million by manually mining the literature and integrating six database resources with evidence from experimental and computational sources. Overall, RNAInter will provide a more comprehensive and readily accessible RNA interactome platform to investigate the regulatory landscape of cellular RNAs.

The progression of cancer is accompanied by the acquisition of stemness features. Many stemness evaluation methods based on transcriptional profiles have been presented to reveal the relationship between stemness and cancer. However, instead of absolute stemness index values—the values with certain range—these methods gave the values without range, which makes them unable to intuitively evaluate the stemness. Besides, these indices were based on the absolute expression values of genes, which were found to be seriously influenced by batch effects and the composition of samples in the dataset. Recently, we have showed that the signatures based on the relative expression orderings (REOs) of gene pairs within a sample were highly robust against these factors, which makes that the REO-based signatures have been stably applied in the evaluations of the continuous scores with certain range. Here, we provided an absolute REO-based stemness index to evaluate the stemness. We found that this stemness index had higher correlation with the culture time of the differentiated stem cells than the previous stemness index. When applied to the cancer and normal tissue samples, the stemness index showed its significant difference between cancers and normal tissues and its ability to reveal the intratumor heterogeneity at stemness level. Importantly, higher stemness index was associated with poorer prognosis and greater oncogenic dedifferentiation reflected by histological grade. All results showed the capability of the REO-based stemness index to assist the assignment of tumor grade and its potential therapeutic and diagnostic implications.

Fine particulate matter (PM) levels, carbon dioxide (CO) levels and particle-number concentrations (PNC) were monitored in train carriages on seven routes of the mass transit railway in Hong Kong between March and May 2014, using real-time monitoring instruments. The 8-h average PM levels in carriages on the seven routes ranged from 24.1 to 49.8 µg/m, higher than levels in Finland and similar to those in New York, and in most cases exceeding the standard set by the World Health Organisation (25 µg/m). The CO concentration ranged from 714 to 1801 ppm on four of the routes, generally exceeding indoor air quality guidelines (1000 ppm over 8 h) and reaching levels as high as those in Beijing. PNC ranged from 1506 to 11,570 particles/cm, lower than readings in Sydney and higher than readings in Taipei. Correlation analysis indicated that the number of passengers in a given carriage did not affect the PM concentration or PNC in the carriage. However, a significant positive correlation (p < 0.001, R = 0.834) was observed between passenger numbers and CO levels, with each passenger contributing approximately 7.7-9.8 ppm of CO. The real-time measurements of PM and PNC varied considerably, rising when carriage doors opened on arrival at a station and when passengers inside the carriage were more active. This suggests that air pollutants outside the train and passenger movements may contribute to PM levels and PNC. Assessment of the risk associated with PM exposure revealed that children are most severely affected by PM pollution, followed in order by juveniles, adults and the elderly. In addition, females were found to be more vulnerable to PM pollution than males (p < 0.001), and different subway lines were associated with different levels of risk.

Aquatic fireflies are important indicators of the quality of freshwater environments and key models for research on insect adaptation to freshwater environments. For these investigations, gene expression analyses using quantitative real-time PCR are heavily dependent on reliable reference genes. In this study, based on a transcriptome assembly and annotation for the aquatic firefly Aquatica leii at the adult and larval stages, 10 candidate reference genes (α- tubulin , β- tubulin , β- actin , EF1A , SDHA , UBQ , GST , GAPDH , RPS31 , and RPL13A ) were identified for analyses of expression stability. Quantitative real-time PCR analyses for each candidate reference genes in A. leii was conducted for four developmental stages, four adult tissue types, two adult sexes, and two ecological stressors [adults exposed to five temperatures and larvae exposed to four concentrations of benzo(a)pyrene]. Results were evaluated by three independent algorithms (geNorm, NormFinder, and BestKeeper) and one comparative algorithm (RefFinder). The expression stability of candidate reference genes in A. leii differed under various conditions. Reference genes with the most stable expressions levels in different tissues, temperatures, sexes, developmental stages, and concentrations of benzo(a)pyrene were α- tubulin , GST , β- actin , β- tubulin , and α- tubulin , respectively. Furthermore, the optimal normalization factors (NFs) for the quantification of the expression levels of target genes by quantitative real-time PCR analyses of A. leii were identified for each experimental group. In particular, NF = 2 for different tissues (α- tubulin + β- tubulin ), different sexes (β- actin + EF1A ), and larvae exposed to different concentrations of benzo(a)pyrene (α- tubulin + EF1A ); NF = 3 for developmental stages ( GST + GAPDH + SDHA ) and adults exposed to different temperatures (β- tubulin + EFA + GST ). In addition, we surveyed the expression profiles of two target genes ( CYP3A and CSP8 ) in larvae exposed to different concentrations of benzo(a)pyrene and in different adult tissues. The results further validated the reliability of the reference genes. The optimal reference genes for various experimental conditions identified in these analyses provide a useful tool for ecological studies o...

Aim: To evaluate henagliflozin, a novel sodium-glucose co-transporter-2 inhibitor, as monotherapy in patients with type 2 diabetes and inadequate glycaemic control with diet and exercise.Materials and Methods: This multicentre trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period.Four hundred and sixty-eight patients with an HbA1c of 7.0%-10.5% were randomly assigned (1:1:1) to receive once-daily placebo, or 5 or 10 mg henagliflozin. After 24 weeks, patients on placebo were switched to 5 or 10 mg henagliflozin, and patients on henagliflozin maintained the initial therapy. The primary endpoint was the change in HbA1c from baseline after 24 weeks.Results: At Week 24, the placebo-adjusted least squares (LS) mean changes from baseline in HbA1c were −0.91% (95% CI: −1.11% to −0.72%; P < .001) and −0.94% (−1.13% to −0.75%; P < .001) with henagliflozin 5 and 10 mg, respectively; the placebo-adjusted LS mean changes were −1.3 (−1.8 to −0.9) and −1.5 (−2.0 to −1.1) kg in body weight, and −5.1 (−7.2 to −3.0) and −4.4 (−6.5 to −2.3) mmHg in systolic blood pressure (all P < .05). The trends of these improvements were sustained for an additional 28 weeks. Adverse events occurred in 81.0%, 78.9% and 78.9% of patients in the placebo, henagliflozin 5 and 10 mg groups, respectively. No diabetic ketoacidosis or major episodes of hypoglycaemia occurred.Conclusions: Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated.