In recent years, several studies have reported monocyte lymphocyte ratio (MLR) to predict prognosis in various tumors. Our study was performed to evaluate the association between preoperative MLR between prognostic variables in urothelial carcinoma patients. Systematic literature search was conducted in PubMed, Embase, Web of science. The correlation between preoperative MLR and overall survival (OS), cancer specific survival (CSS), disease free survival (DFS)/relapse free survival (RFS), progression free survival(PFS) was evaluated in urothelial carcinoma patients. Meanwhile, the association between MLR and clinicopathological characteristics was assessed. Finally, 12 comparative studies comprising a total of 6209 patients were included for pooled analysis. The hazard ratios (HRs), odds ratios (ORs)and 95% confidence intervals (CIs) were further analyzed as effect measures. The pooled results demonstrated that elevated preoperative MLR indicated unfavorable OS (HR = 1.29, 95%CI = 1.18-1.39, I2 = 33.6%), DFS/RFS (HR = 1.42, 95%CI = 1.30-1.55, I2 = 0.0%) and CSS (HR = 1.41, 95%CI = 1.29-1.52, I2 = 0.0%). Moreover, the pooled results also suggested that elevated preoperative MLR was correlated with high tumor stage (OR = 1.22, 95%CI = 1.07-1.37, I2 = 0.0%) in urothelial carcinoma patients. No significant association was found between preoperative MLR and PFS in upper urinary tract urothelial carcinoma (UUTUC) patients. Collectively, elevated preoperative MLR predicted poor prognosis in urothelial carcinoma and have the potential to be a feasible and cost-effective prognostic predictor for management of urothelial carcinoma.

The effect of pre-operative renal insufficiency on urothelial carcinoma (UC) prognosis has been investigated by numerous studies. While the majority report worse UC outcomes in patients with renal insufficiency, the results between the studies differed wildly. To enable us to better estimate the prognostic value of renal insufficiency on UC, we performed a systematic review and meta-analysis based on the published literature. A total of 16 studies which involved 5,232 patients with UC, investigated the relationship between pre-operative renal insufficiency and disease prognosis. Estimates of combined hazard ratio (HR) for bladder urothelial carcinoma recurrence, cancer-specific survival (CSS) and overall survival (OS) were 1.65 (95% CI, 1.11-2.19), 1.59 (95% CI, 1.14-2.05) and 1.45 (95% CI, 1.19-1.71), respectively; and for upper urinary tract urothelial carcinoma recurrence, CSS and OS were 2.27 (95% CI, 1.42-3.12), 1.02 (95% CI, 0.47-1.57) and 1.52 (95% CI, 1.05-1.99), respectively. Our results indicate that UC patients with pre-operative renal insufficiency tend to have higher recurrence rates and poorer survival compared to those with clinically normal renal function, thus renal function should be closely monitored in these patients. The impact of intervention for renal insufficiency on the prognosis of UC needs to be further studied.

An increasing number of studies have highlighted the potential link between EXO1 polymorphisms and cancer risk, although no consensus has yet been obtained. Thus, we aimed to obtain a thorough and current assessment of EXO1 polymorphisms and cancer susceptibility by performing a meta-analysis. A comprehensive literature retrieval was performed on PubMed, EMbase, Web of Science and Wanfang databases. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the results. Finally, 39 case-control studies of the nine EXO1 polymorphisms that involved 21,651 cases and 21,348 controls met our inclusion criteria. The pooled analysis indicated that the rs1047840 polymorphism conferred a significantly increased susceptibility to cancer in an allelic model. Similarly, the rs3754093, rs1776177, rs9350, rs10802996, rs1635498, rs1776148 and rs851797 polymorphisms were also associated with an increased susceptibility to cancer in an allelic model, respectively, while no significant association was identified for rs1635517 polymorphism. For the rs1047840 polymorphism, in an ethnicity subgroup analysis, a significantly increased susceptibility to cancer for Asians was identified in all the genetic models, and for Caucasians in an allelic model. Our findings provide the evidence that the rs1047840, rs9350, rs10802996, rs1635498, rs1776148, rs1776177, rs3754093 and rs851797 polymorphisms may act as risk factors for cancer.

Inconsistent findings have reported on the inflammatory potential of diet and cardiovascular disease (CVD) and mortality risk. The aim of this meta-analysis was to investigate the association between the inflammatory potential of diet as estimated by the dietary inflammatory index (DII) score and CVD or mortality risk in the general population. A comprehensive literature search was conducted in PubMed and Embase databases through February 2017. All prospective observational studies assessing the association of inflammatory potential of diet as estimated by the DII score with CVD and all-cause, cancer-related, cardiovascular mortality risk were included. Nine prospective studies enrolling 134,067 subjects were identified. Meta-analyses showed that individuals with the highest category of DII (maximal pro-inflammatory) was associated with increased risk of all-cause mortality (hazard risk [HR] 1.22; 95% confidence interval [CI] 1.06-1.41), cardiovascular mortality (RR 1.24; 95% CI 1.01-1.51), cancer-related mortality (RR 1.28; 95% CI 1.04-1.58), and CVD (RR 1.32; 95% CI 1.09-1.60) than the lowest DII score. More pro-inflammatory diets, as estimated by the higher DII score are independently associated with an increased risk of all-cause, cardiovascular, cancer-related mortality, and CVD in the general population, highlighting low inflammatory potential diet may reduce mortality and CVD risk.

Circular RNAs (circRNAs), a new class of regulatory noncoding RNAs, play important roles in human diseases. While a growing number of circRNAs have been characterized with biological functions, it is necessary to integrate all the information to facilitate studies on circRNA functions and regulatory networks in human diseases. Circ2Disease database contains 273 manually curated associations between 237 circRNAs and 54 human diseases with strong experimental evidence from 120 studies. Each association includes circRNA name, disease name, expression pattern, experimental method, a brief functional description of the circRNA-disease relationship, and other detailed information. The experimentally validated miRNAs that may be 'sponged up' by these circRNAs and their validated targets were also integrated to form a comprehensive regulatory network. Circ2Disease provides a user-friendly interface to browse, search, analyze regulatory network and download data. With the rapidly increasing interest in circRNAs, Circ2Disease will significantly improve our understanding of circRNA deregulation in diseases and is a useful resource for studying posttranscriptional regulatory roles of circRNAs in human diseases.

Gene expression is negatively regulated by microRNAs (miRNAs), which commonly act as tumor oncogenes or suppressors. Previous results were inconsistent concerning the relationship between polymorphisms in miRNAs and risk of urological neoplasms. Here, we conducted a comprehensive literature research on diverse databases aiming at enrolling all eligible studies up to August 31, 2016. A total of 13 publications comprising 29 case-control studies were enrolled for three polymorphisms in three miRNAs. Overall analyses suggested significant associations between miR-146a rs2910164 polymorphism and urological neoplasms risk in allelic, homozygote and recessive models. In the stratified analysis by ethnicity, we uncovered a significant association between rs2910164 polymorphism and risk of urological neoplasms in Asian populations in allelic, homozygote and recessive models. Highlighted, when stratified analysis was conducted by cancer type, rs2910164 polymorphism was also significantly associated with an increased risk of bladder cancer in allelic, homozygote and recessive models. Although for rs11614913 and rs3746444 polymorphisms, overall analyses suggested negative results, for rs11614913 polymorphism, when subgroup analysis was conducted by cancer type, a significantly decreased risk of renal cell cancer was identified in recessive model. In brief, current work indicated that miR-146a rs2910164 polymorphism is a risk factor for urological neoplasms, particularly for bladder cancer.

Periodontal disease is a common oral health problem in the elderly population. The prevalence varied substantially due to absence of a universal diagnostic criteria. We conducted a systematic review to identify the epidemiological characteristics of periodontal diseases among Chinese elderly people. A total of 19 articles were included. The pooled detection rates for three indicators, including bleeding on probing (BOP), pocket depth (PD) and clinical attachment loss (CAL), were 53.9% (95% CI: 43.8-63.9%), 57.0% (50.8-63.2%), and 70.1% (65.4-74.8%), respectively. No significant differences in these indicators between urban and rural population. When stratified by gender, BOP (+) detection rates did not show any differences, but the detection rates of PD ≥ 4 mm and CAL ≥ 4 mm were significantly higher in males than in females (59.3% [53.4-65.2%] versus 50.8% [43.5-58.0%], RRPD = 1.13 [1.01-1.26]; 73.8% [70.0-77.7%] versus 65.2% [60.2-70.2%], RRCAL = 1.21 [1.11-1.32]). No statistically significant differences were observed between CAL ≥ 4 mm and PD ≥ 4 mm (RR = 1.12, [0.83-1.50]). A geographical map based on available data during 1987-2015 showed wide variations of periodontal disease across the mainland China. Some factors such as heterogeneity of case definitions, no specific diagnosis of periodontitis, and variable quality of the included studies could affect the final results. Hence, further high-quality epidemiological studies with standardized diagnostic criteria are needed.

Early childhood caries (ECC) is the most common chronic disease in young children. A reliable predictive model for ECC prevalence is needed in China as a decision supportive tool for planning health resources. In this study, we first established the autoregressive integrated moving average (ARIMA) model and grey predictive model (GM) based on the estimated national prevalence of ECC with meta-analysis from the published articles. The pooled data from 1988 to 2010 were used to establish the model, while the data from 2011 to 2013 were used to validate the models. The fitting and prediction accuracy of the two models were evaluated by mean absolute error (MAE) and mean absolute percentage error (MAPE). Then, we forecasted the annual prevalence from 2014 to 2018, which was 55.8%, 53.5%, 54.0%, 52.9%, 51.2% by ARIMA model and 52.8%, 52.0%, 51.2%, 50.4%, 49.6% by GM. The declining trend in ECC prevalence may be attributed to the socioeconomic developments and improved public health service in China. In conclusion, both ARIMA and GM models can be well applied to forecast and analyze the trend of ECC; the fitting and testing errors generated by the ARIMA model were lower than those obtained from GM.

The prognostic value of miR-17-92 cluster high-expression in various tumors remains controversial. Therefore, we conducted this meta-analysis by searching literatures in PubMed, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure to identify eligible studies. Eventually, we analyzed 36 articles that examined 17 tumor types from 4965 patients. Consequently, high-expression of miR-17-92 cluster in various tumors was associated with unfavorable overall survival in both univariate (HR = 2.05, 95%CI: 1.58-2.65, P<0.001) and multivariate (HR = 2.14, 95%CI: 1.75-2.61, P<0.001) analyses. Likewise, similar results were found in different subgroups of country, test method, miR-17-92 cluster component, sample source and size. Additionally, high-expression of miR-17-92 cluster was linked with poor disease-free survival (Univariate: HR = 1.96, 95%CI: 1.55-2.48, P<0.001; Multivariate: HR = 2.18, 95%CI: 1.63-2.91, P<0.001), favorable progression-free survival (Univariate: HR = 0.36, 95%CI: 0.16-0.80, P = 0.012; Multivariate: HR = 1.55, 95%CI: 0.79-3.05, P = 0.201) and poor cancer specific survival in univariate rather than multivariate analyses (Univariate: HR = 1.77, 95%CI: 1.21-2.60, P = 0.004; Multivariate: HR = 1.77, 95%CI: 0.80-3.92, P = 0.160). However, no association of miR-17-92 cluster high-expression was detected with recurrence or relapse-free survival. In summary, this meta-analysis towards high-expression of miR-17-92 cluster has indicated poor prognosis of various cancers. Notably, future studies comprising large cohort size from multicenter are required to confirm our conclusions.

Hand, foot, and mouth disease (HFMD) is a common childhood illness caused by enteroviruses. We analyzed the pathogenic characteristics of HFMD in Shaanxi province, China, during 2010-2016. Clinical samples were collected from HFMD cases. Real-time PCR and RT-PCR were used to identify the enterovirus(EVs) serotypes. Viral RNA sequences were amplified using RT-PCR and compared by phylogenetic analysis. Descriptive epidemiological methods were used to analyze. A total of 16,832 HFMD positive cases were confirmed in the laboratory. EV-A71 and CV-A16 were the main pathogens in 2010. EV-A71 was the dominant pathogen in the periods of 2011 to 2012 and 2014, 2016. In 2013 and 2015, other EVs increased greatly, in which CV-A6 was the predominant pathogen. EV-A71 was more frequently detected in deaths and severe cases. Phylogenetic analysis revealed that EV-A71 belonged to the C4a evolution branch of C4 sub-genotype and CV-A16 belonged to the B1a or B1b evolution branch of B1 sub-genotype, whereas CV-A6 strains were assigned to D2 or D3 sub-genotype. The pathogen spectrum of HFMD has changed in 7 years, and the major serotypes EV-A71, CV- A16 and CV- A6 alternated or co-circulated. Long-term surveillance and research of EVs should be strengthened for the prevention and control of HFMD.

Under hypoxic conditions, the expression of Vitreoscilla hemoglobin (VHb) in plants is proposed to increase the productivity of certain oxygen-requiring metabolic pathways by promoting the delivery of oxygen. Tropane alkaloids (TAs) are a class of important plant secondary metabolites with significant medicinal value; the final step in their biosynthesis requires oxygen. Whether heterologous expression of VHb, especially in different subcellular compartments, can accelerate the accumulation of TAs is not known. Herein, the effect of heterologous expression of VHb in different subcellular locations on the TA profile of H. niger hairy roots was investigated. The targeted expression of VHb in the plastids (using pVHb-RecA construct), led to the accumulation of 197.68 μg/g hyoscyamine in the transgenic H. niger hairy roots, which was 1.25-fold of the content present in the lines in which VHb expression was not targeted, and 3.66-fold of that present in the wild type (WT) lines. The content of scopolamine was increased by 2.20- and 4.70-fold in the pVHb-RecA transgenic lines compared to that in the VHb transgenic and WT lines. Our results demonstrate that VHb could stimulate the accumulation of TAs in the transgenic H. niger hairy roots. Quantitative RT-PCR analysis revealed that the expression of key genes involved in TA biosynthesis increased significantly in the VHb transgenic lines. We present the first description of a highly efficient strategy to increase TA content in H. niger. Moreover, our results also shed light on how the production of desired metabolites can be efficiently enhanced by using more accurate and appropriate genetic engineering strategies.

The discovery of fall armyworm, a native of the Western Hemisphere, in western Africa in 2016 was rapidly followed by detections throughout sub-Saharan Africa, India, and most recently southeastern Asia. This moth pest has a broad host range that threatens such important crops as corn, rice, millet, and sorghum, creating concern for its potential impact on agriculture in the Eastern Hemisphere. Although genetic data suggest populations sampled in Africa and India originate from a recent common source, it is not known whether this is the case for populations in southeastern Asia, nor whether the subgroup with a preference for rice and millet is present in the region. This study found through comparisons of genetic markers that the fall armyworm from Myanmar and southern China are closely related to those from Africa and India, suggesting a common origin for these geographically distant populations. The results are consistent with a single recent introduction into the Eastern Hemisphere followed by rapid dispersion. The molecular similarities include discrepancies between the genetic markers that brings into question whether the subpopulation most likely to be a threat to rice and millet is present in significant numbers in Asia.

A novel strain LTYR-11ZT that exhibited multiple plant growth promoting (PGP) traits was isolated from the surface-sterilized leaves of Alhagi sparsifolia Shap. (Leguminosae), which reprsents one of the top drought tolerant plants in north-west China. Phylogenetic analysis of 16S rRNA gene sequences and multilocus sequence analysis based on partial sequences of atpD, gyrB, infB and rpoB genes revealed that strain LTYR-11ZT was a member of the genus Pantoea, with Pantoea theicola NBRC 110557T and Pantoea intestinalis DSM 28113T as the closest phylogenetic relatives. The results of DNA-DNA hybridization, phenotypic tests and fatty acid analysis confirmed that strain LTYR-11ZT represents a novel species of the genus Pantoea, for which we propose the name Pantoea alhagi sp. nov. Confocal microscopy observation revealed that strain LTYR-11ZT effectively colonizes the rhizoplane of both Arabidopsis and wheat. Strain LTYR-11ZT was able to promote the growth of wheat enhancing its resistance to drought stress. Strain LTYR-11ZT led to increased accumulation of soluble sugars, decreased accumulation of proline and malondialdehyde (MDA), and decreased degradation of chlorophyll in leaves of drought-stressed wheat. Our findings will contribute to the development of a novel biotechnological agent to improve the adaptation of crop plants to drought in arid ecosystems.

Understanding the population structure and movements of the invasive fall armyworm (FAW, Spodoptera frugiperda) is important as it can help mitigate crop damage, and highlight areas at risk of outbreaks or evolving insecticide resistance. Determining population structure in invasive FAW has been a challenge due to genetic mutations affecting the markers traditionally used for strain and haplotype identification; mitochondrial cytochrome oxidase I (COIB) and the Z-chromosome-linked Triosephosphate isomerase (Tpi). Here, we compare the results from COIB and Tpi markers with highly variable repeat regions (microsatellites) to improve our understanding of FAW population structure in Africa. There was very limited genetic diversity using the COIB marker, whereas using the TpiI4 marker there was greater diversity that showed very little evidence of genetic structuring between FAW populations across Africa. There was greater genetic diversity identified using microsatellites, and this revealed a largely panmictic population of FAW alongside some evidence of genetic structuring between countries. It is hypothesised here that FAW are using long-distance flight and prevailing winds to frequently move throughout Africa leading to population mixing. These approaches combined provide important evidence that genetic mixing between invasive FAW populations may be more common than previously reported.

Constitutive androstane receptor (CAR) regulates hepatic xenobiotic and energy metabolism, as well as promotes cell growth and hepatocarcinogenesis. Berberine is an ancient multipotent alkaloid drug which derived from Coptis chinensis plants. Here we report that berberine is able to be cellular uptake and accessible to chromatin in human hepatoma HepG2 cells. Berberine induces more apoptosis, cell cycle arrest, but less ROS production in CAR overexpressed mCAR-HepG2 cells. Moreover, berberine inhibits expressions of CAR and its target genes CYP2B6 and CYP3A4. Furthermore, berberine enhances DNA methylation level in whole genome but reduces that in promoter regions CpG sites of CYP2B6 and CYP3A4 genes under the presence of CAR condition. These results indicated that the antiproliferation of berberine might be mediated by the unique epigenetic modifying mechanism of CAR metabolic pathway, suggesting that berberine is a promising candidate in anticancer adjuvant chemotherapy, due to its distinct pharmacological properties in clinic.

Salvia miltiorrhiza Bunge, which contains tanshinones and phenolic acids as major classes of bioactive components, is one of the most widely used herbs in traditional Chinese medicine. Production of tanshinones and phenolic acids is enhanced by methyl jasmonate (MeJA). Transcription factor MYC2 is the switch of jasmontes signaling in plants. Here, we focused on two novel JA-inducible genes in S. miltiorrhiza, designated as SmMYC2a and SmMYC2b, which were localized in the nucleus. SmMYC2a and SmMYC2b were also discovered to interact with SmJAZ1 and SmJAZ2, implying that the two MYC2s might function as direct targets of JAZ proteins. Ectopic RNA interference (RNAi)-mediated knockdown experiments suggested that SmMYC2a/b affected multiple genes in tanshinone and phenolic acid biosynthetic pathway. Besides, the accumulation of tanshinones and phenolic acids was impaired by the loss of function in SmMYC2a/b. Meanwhile, SmMYC2a could bind with an E-box motif within SmHCT6 and SmCYP98A14 promoters, while SmMYC2b bound with an E-box motif within SmCYP98A14 promoter, through which the regulation of phenolic acid biosynthetic pathway might achieve. Together, these results suggest that SmMYC2a and SmMYC2b are JAZ-interacting transcription factors that positively regulate the biosynthesis of tanshinones and Sal B with similar but irreplaceable effects.

Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis, a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines.

Large scale greigite with uniform dimensions has stimulated significant demands for applications such as hyperthermia, photovoltaics, medicine and cell separation, etc. However, the inhomogeneity and hydrophobicity for most of the as prepared greigite crystals has limited their applications in biomedicine. Herein, we report a green chemical method utilizing β-cyclodextrin (β-CD) and polyethylene glycol (PEG) to synthesize bioinspired greigite (Fe₃S₄) magnetic nanocrystals (GMNCs) with similar structure and magnetic property of magnetosome in a large scale. β-CD and PEG is responsible to control the crystal phase and morphology, as well as to bound onto the surface of nanocrystals and form polymer layers. The GMNCs exhibit a transverse relaxivity of 94.8 mM⁻¹ s⁻¹ which is as high as iron oxide nanocrystals, and an entrapment efficiency of 58.7% for magnetic guided delivery of chemotherapeutic drug doxorubicin. Moreover, enhanced chemotherapeutic treatment of mice tumor was obtained via intravenous injection of doxorubicin loaded GMNCs.

Salusin β is a multifunctional bioactive peptide and is considered as a promising candidate biomarker for predicting atherosclerotic cardiovascular diseases. The present study was designed to investigate the roles and mechanisms of salusin β in the paraventricular nucleus (PVN) in attenuating hypertension and hypothalamic inflammation and whether central salusin β blockade has protective effects in essential hypertension. Normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were used in this study. The rats were chronic PVN infusion either specific salusin β blocker, antisalusin β IgG (SIgG), or control IgG (CIgG) for 2 weeks. Hypertensive rats had significantly increased salusin β expression compared with normotensive rats. Central blockade of salusin β attenuated hypertension, reduced circulating norepinephrine (NE) levels, and improved cardiac hypertrophy and function in hypertensive rats. Salusin β blockade significantly reduced proinflammatory cytokines (PICs), nuclear factor-kappa B (NF-κB) activity, reactive oxygen species (ROS) levels, and altered renin-angiotensin system (RAS) components in the PVN of hypertensive rats. These findings suggest that the beneficial effects of salusin β blockade in essential hypertension are possibly due to down-regulate of inflammatory molecules and ROS in the PVN.

The biological toxicity of high levels of breathing gases has been known for centuries, but the mechanism remains elusive. Earlier work mainly focused on the influences of dispersed gas molecules dissolved in water on biomolecules. However, recent studies confirmed the existence of aggregated gas molecules at the water-solid interface. In this paper, we have investigated the binding preference of aggregated gas molecules on proteins with molecular dynamics simulations, using nitrogen (N₂) gas and the Src-homology 3 (SH3) domain as the model system. Aggregated N₂ molecules were strongly bound by the active sites of the SH3 domain, which could impair the activity of the protein. In contrast, dispersed N₂ molecules did not specifically interact with the SH3 domain. These observations extend our understanding of the possible toxicity of aggregates of gas molecules in the function of proteins.