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Hepatocellular carcinoma (HCC) is one of the most commonly cancers with poor prognosis and drug response. Identifying accurate therapeutic targets would facilitate precision treatment and prolong survival for HCC. In this study, we analyzed liver hepatocellular carcinoma (LIHC) RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA), and identified PARD3 as one of the most significantly differentially expressed genes (DEGs). Then, we investigated the relationship between PARD3 and outcomes of HCC, and assessed predictive capacity. Moreover, we performed functional enrichment and immune infiltration analysis to evaluate functional networks related to PARD3 in HCC and explore its role in tumor immunity. PARD3 expression levels in 371 HCC tissues were dramatically higher than those in 50 paired adjacent liver tissues (p p = 0.002), vascular invasion (p = 0.012) and TP53 mutation (p = 0.009). Elevated PARD3 expression also correlated with lower overall survival (OS, HR = 2.08, 95% CI = 1.45–2.98, p p = 0.003). 242 up-regulated and 71 down-regulated genes showed significant association with PARD3 expression, which were involved in genomic instability, response to metal ions, and metabolisms. PARD3 is involved in diverse immune infiltration levels in HCC, especially negatively related to dendritic cells (DCs), cytotoxic cells, and plasmacytoid dendritic cells (pDCs). Altogether, PARD3 could be a potential prognostic biomarker and therapeutic target of HCC.

Preterm infants with bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH) have accelerated lung aging and poor long-term outcomes. Klotho is an antiaging protein that modulates oxidative stress, angiogenesis and fibrosis. Here we test the hypothesis that decreased cord Klotho levels in preterm infants predict increased BPD–PH risk and early Klotho supplementation prevents BPD-like phenotype and PH in rodents exposed to neonatal hyperoxia. In experiment 1, Klotho levels were measured in cord blood of preterm infants who were enrolled in a longitudinal cohort study. In experiment 2, using an experimental BPD–PH model, rat pups exposed to room air or hyperoxia (85% O2) were randomly assigned to receive every other day injections of recombinant Klotho or placebo. The effect of Klotho on lung structure, PH and cardiac function was assessed. As compared to controls, preterm infants with BPD or BPD–PH had decreased cord Klotho levels. Early Klotho supplementation in neonatal hyperoxia-exposed rodents preserved lung alveolar and vascular structure, attenuated PH, reduced pulmonary vascular remodeling and improved cardiac function. Together, these findings have important implications as they suggest that perinatal Klotho deficiency contributes to BPD–PH risk and strategies that preserve Klotho levels, may improve long-term cardiopulmonary outcomes in preterm infants.

Jatropha curcas, an economically important biofuel feedstock with oil-rich seeds, has attracted considerable attention among researchers in recent years. Nevertheless, valuable information on the yield component of this plant, particularly regarding ovule development, remains scarce. In this study, transcriptome profiles of anther and ovule development were established to investigate the ovule development mechanism of J. curcas. In total, 64,325 unigenes with annotation were obtained, and 1723 differentially expressed genes (DEGs) were identified between different stages. The DEG analysis showed the participation of five transcription factor families (bHLH, WRKY, MYB, NAC and ERF), five hormone signaling pathways (auxin, gibberellic acid (GA), cytokinin, brassinosteroids (BR) and jasmonic acid (JA)), five MADS-box genes (AGAMOUS-2, AGAMOUS-1, AGL1, AGL11, and AGL14), SUP and SLK3 in ovule development. The role of GA and JA in ovule development was evident with increases in flower buds during ovule development: GA was increased approximately twofold, and JA was increased approximately sevenfold. In addition, the expression pattern analysis using qRT-PCR revealed that CRABS CLAW and AGAMOUS-2 were also involved in ovule development. The upregulation of BR signaling genes during ovule development might have been regulated by other phytohormone signaling pathways through crosstalk. This study provides a valuable framework for investigating the regulatory networks of ovule development in J. curcas.

Understanding the composition of a genetically-encoded (GE) library is instrumental to the success of ligand discovery. In this manuscript, we investigate the bias in GE-libraries of linear, macrocyclic and chemically post-translationally modified (cPTM) tetrapeptides displayed on the M13KE platform, which are produced via trinucleotide cassette synthesis (19 codons) and NNK-randomized codon. Differential enrichment of synthetic DNA {S}, ligated vector {L} (extension and ligation of synthetic DNA into the vector), naïve libraries {N} (transformation of the ligated vector into the bacteria followed by expression of the library for 4.5 hours to yield a “naïve” library), and libraries chemically modified by aldehyde ligation and cysteine macrocyclization {M} characterized by paired-end deep sequencing, detected a significant drop in diversity in {L} → {N}, but only a minor compositional difference in {S} → {L} and {N} → {M}. Libraries expressed at the N-terminus of phage protein pIII censored positively charged amino acids Arg and Lys; libraries expressed between pIII domains N1 and N2 overcame Arg/Lys-censorship but introduced new bias towards Gly and Ser. Interrogation of biases arising from cPTM by aldehyde ligation and cysteine macrocyclization unveiled censorship of sequences with Ser/Phe. Analogous analysis can be used to explore library diversity in new display platforms and optimize cPTM of these libraries.

Recently, numerous genome wide association studies (GWAS) and other case-control association studies examining the relationship between interleukin-7 receptor α chain (IL7RA) gene rs3194051, rs987107, rs11567686, and rs11567685 variants and multiple sclerosis (MS) risk have been conducted, but the conclusions have been inconsistent. The main objective of this meta-analysis was to more precisely explore the association of these four IL7RA variants with MS development. Twenty-seven eligible studies involving 9734 cases and 10436 controls were included in the present meta-analysis. Power calculation, publication bias, sensitivity analysis and cumulative meta-analysis were performed to derive a reliable conclusion. Our study indicated three IL7RA loci were significantly associated with increasing MS risk (rs3194051: recessive model: OR = 1.22, 95% CI 1.08–1.38; rs987107: recessive model: OR = 1.44, 95% CI 1.22–1.69; and rs11567686: dominant model: OR = 1.18, 95% CI 1.01–1.37). Additionally, IL7RA rs11567685 variants might not be related to MS development. In all, IL7RA locus polymorphisms could play an important role in the predisposition to MS, which could contribute to a better understanding the pathogenesis of multiple sclerosis.

KRAS mutations are abnormalities widely found in genomic DNA and circulating tumor DNA (ctDNA) of various types of cancers. Thus, highly sensitive detection of KRAS mutations in genomic DNA is of great significance in disease diagnosis and personalized medicine. Here, we developed a ligation-initiated loop-mediated isothermal amplification (LAMP) assaying method for ultrasensitive detection of KRAS mutation. In the presence of mutant KRAS DNA (mutDNA), the dumbbell-shaped structure (DSS) is formed by the specific ligation of two substrates (SLS1 and SLS2), which act as a template to initiate the following LAMP amplification. Making use of the outstanding specificity of ligation reaction and superior amplification of LAMP, 10 aM mutDNA can be accurately determined. In addition, as low as 0.1% mutDNA can be detected in the presence of a large excess of wild-type KRAS DNA (wtDNA), indicating the high sensitivity and specificity of the method. Furthermore, this strategy has been successfully applied for detection of a KRAS mutation from tissue samples of colorectal cancer patients. Thus, the developed ligation-initiated LAMP fluorescence assaying strategy presents a promising prospect for ultrasensitive detection of mutations.

A series of Ti/Li/Al ternary layered double hydroxides (TiLiAl-LDHs) with different Ti:Li:Al molar ratios were prepared by a coprecipitation method for photocatalytic CO2 reduction. It was demonstrated that the contents of anions between the layers of Ti/Li/Al-LDHs greatly determined the photocatalytic activity for CO2 reduction. With Ti:Li:Al molar ratios optimized to be 1:3:2, the largest contents of \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\bf{CO}}}_{{\bf{3}}}^{{\bf{2}}}$$\end{document}CO32− anion and hydroxyl group were obtained for the Ti1Li3Al2-LDHs sample, which exhibited the highest photocatalytic activity for CO2 reduction, with CH4 production rate achieving 1.33 mmol h−1 g−1. Moreover, the theoretical calculations show that Ti1Li3Al2-LDHs is a p-type semiconductor with the narrowest band gap among all the obtained TiLiAl-LDHs. After calcined at high temperatures such as 700 °C, and the obtained TiLiAl-700 sample showed much increased photocatalytic activity for CO2 reduction, with CH4 production rate reaching about 1.59 mmol h−1 g−1. This calcination induced photocatalytic enhancement should be related to the cystal structure transformation from hydrotalcite to mixed oxides containing high reactive oxygen species for more efficient CO2 reduction.

Iron oxide nanoparticles (IONPs) have been increasingly used in biomedical applications, but the comprehensive understanding of their interactions with biological systems is relatively limited. In this study, we systematically investigated the in vitro cell uptake, cytotoxicity, in vivo distribution, clearance and toxicity of commercially available and well-characterized IONPs with different sizes and coatings. Polyethylenimine (PEI)-coated IONPs exhibited significantly higher uptake than PEGylated ones in both macrophages and cancer cells, and caused severe cytotoxicity through multiple mechanisms such as ROS production and apoptosis. 10 nm PEGylated IONPs showed higher cellular uptake than 30 nm ones, and were slightly cytotoxic only at high concentrations. Interestingly, PEGylated IONPs but not PEI-coated IONPs were able to induce autophagy, which may play a protective role against the cytotoxicity of IONPs. Biodistribution studies demonstrated that all the IONPs tended to distribute in the liver and spleen, and the biodegradation and clearance of PEGylated IONPs in these tissues were relatively slow (>2 weeks). Among them, 10 nm PEGylated IONPs achieved the highest tumor uptake. No obvious toxicity was found for PEGylated IONPs in BALB/c mice, whereas PEI-coated IONPs exhibited dose-dependent lethal toxicity. Therefore, it is crucial to consider the size and coating properties of IONPs in their applications.

Osteoporosis is a common age-related disorder leading to an increase in osteoporotic fractures and resulting in significant suffering and disability. Inflammation may contribute to osteoporosis, as it does to many other chronic diseases. We examined whether inflammation is etiologically relevant to osteoporosis, assessed from bone mineral density (BMD), as a new potential target of intervention, or whether it is a symptom/biomarker of osteoporosis. We obtained genetic predictors of inflammatory markers from genome-wide association studies and applied them to a large genome wide association study of BMD. Using two-sample Mendelian randomization, we obtained unconfounded estimates of the effect of high-sensitivity C-reactive protein (hsCRP) on BMD at the forearm, femoral neck, an d lumbar spine. After removing potentially pleiotropic single nucleotide polymorphisms (SNPs) possibly acting via obesity-related traits, hsCRP, based on 16 SNPs from genes including CRP, was not associated with BMD. A causal relation of hsCRP with lower BMD was not evident in this study.

It has been reported that in patients with operable stage I non-small cell lung cancer (NSCLC), overall survival (OS) is better in those who undergo hypofractionated stereotactic radiation therapy (HSRT) than in those who undergo surgery. However, the reason that HSRT has a better OS has not been fully explored. Here, we analyzed reconstitution kinetics in immune cells in the peripheral blood of NSCLC patients after HSRT. We found that HSRT increased the frequency of total T cells, especially the proportion of CD8+ T cells, but decreased the frequency of inhibitory Tregs. Intracellular staining showed that after HSRT, peripheral CD8+ T cells were transformed into activated T cells, which express high levels of TNF-α, IFN-γ, granzyme B and IL-2. HSRT also increased the production of IL-2, TNF-α, and IFN-γ but down-regulated the production of TGF-β in CD4+ T cells. The frequencies of naïve B cells and double-negative B cells were lower, while the proportions of MZ-like B cells, transitional B cells and plasmablast cells were higher after HSRT. Collectively, our results demonstrate that HSRT activates the peripheral immune response and indicate the dynamic variation in peripheral lymphocytes after HSRT, which is very important for optimizing combination treatments in clinical practice.

Runx2 may play an important role in development of osteoarthritis (OA). However, the specific role of Runx2 in articular chondrocyte function and in OA development in adult mice has not been fully defined. In this study, we performed the destabilization of the medial meniscus (DMM) surgery at 12-week-old mice to induce OA in adult Runx2 Agc1CreER mice, in which Runx2 was specifically deleted in Aggrecan-expressing chondrocytes by administering tamoxifen at 8-weeks of age. Knee joint samples were collected 8- and 12-weeks post-surgery and analyzed through histology, histomorphometry and micro-computed tomography (μCT). Our results showed that severe OA-like defects were observed after DMM surgery in Cre-negative control mice, including articular cartilage degradation and subchondral sclerosis, while the defects were significantly ameliorated in Runx2 Agc1CreER KO mice. Immunohistochemical (IHC) results showed significantly reduced expression of MMP13 in Runx2 Agc1CreER KO mice compared to that in Cre-negative control mice. Results of quantitative reverse-transcription PCR (qRT-PCR) demonstrated that expression of the genes encoding for matrix degradation enzymes was significantly decreased in Runx2 Agc1CreER KO mice. Thus, our findings suggest that inhibition of Runx2 in chondrocytes could at least partially rescue DMM-induced OA-like defects in adult mice.

The objective of the present study was to systematically assess the association between dioxin/2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer incidence and mortality. Systematic literature searches were conducted until July 2015 in Pubmed, Embase and Cochrane library to identify relevant studies. A random-effects model was applied to estimate the pooled odds ratio (OR), risk ratio (RR), standard incidence ratio (SIR) or standard mortality ratio (SMR) for cancer incidence or mortality. In addition, dose-response, meta-regression, subgroup, and publication bias analyses were conducted. Thirty-one studies involving 29,605 cancer cases and 3,478,748 participants were included. Higher external exposure level of TCDD was significantly associated with all cancer mortality (pooled SMR = 1.09, 95% CI: 1.01–1.19, p = 0.04), but not all cancer incidence (pooled RR = 1.01, 95% CI: 0.97–1.06, p = 0.49). Higher blood level of TCDD was both significantly associated with all cancer incidence (pooled RR = 1.57, 95% CI: 1.21–2.04, p = 0.001) and all cancer mortality (pooled SMR = 1.45, 95% CI: 1.25–1.69, p

Scientific Reports 6: Article number: 38012; published online: 29 November 2016; updated: 10 February 2017. The Acknowledgements section in this Article is incomplete. ‘The work was supported by grants from the National Natural Science Foundation of China (Grant Nos 81400371). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The objective of the present study was to systematically assess the association between dioxin/2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and cancer incidence and mortality. Systematic literature searches were conducted until July 2015 in Pubmed, Embase and Cochrane library to identify relevant studies. A random-effects model was applied to estimate the pooled odds ratio (OR), risk ratio (RR), standard incidence ratio (SIR) or standard mortality ratio (SMR) for cancer incidence or mortality. In addition, dose-response, meta-regression, subgroup, and publication bias analyses were conducted. Thirty-one studies involving 29,605 cancer cases and 3,478,748 participants were included. Higher external exposure level of TCDD was significantly associated with all cancer mortality (pooled SMR = 1.09, 95% CI: 1.01–1.19, p = 0.04), but not all cancer incidence (pooled RR = 1.01, 95% CI: 0.97–1.06, p = 0.49). Higher blood level of TCDD was both significantly associated with all cancer incidence (pooled RR = 1.57, 95% CI: 1.21–2.04, p = 0.001) and all cancer mortality (pooled SMR = 1.45, 95% CI: 1.25–1.69, p

MicroRNAs (miRNAs) control gene expression as key negative regulators at the post-transcriptional level. MiR160 plays a pivotal role in Arabidopsis growth and development through repressing expression of its target AUXIN RESPONSE FACTOR (ARF) genes; however, the function of miR160 in monocots remains elusive. In this study, we found that the mature rice miR160 (OsmiR160) was mainly derived from OsMIR160a and OsMIR160b genes. Among four potential OsmiR160 target OsARF genes, the OsARF18 transcript was cleaved at the OsmiR160 target site. Rice transgenic plants (named mOsARF18) expressing an OsmiR160-resistant version of OsARF18 exhibited pleiotropic defects in growth and development, including dwarf stature, rolled leaves and small seeds. mOsARF18 leaves were abnormal in bulliform cell differentiation and epidermal cell division. Starch accumulation in mOsARF18 seeds was also reduced. Moreover, auxin induced expression of OsMIR160a, OsMIR160b and OsARF18, whereas expression of OsMIR160a and OsMIR160b as well as genes involved in auxin signaling was altered in mOsARF18 plants. Our results show that negative regulation of OsARF18 expression by OsmiR160 is critical for rice growth and development via affecting auxin signaling, which will advance future studies on the molecular mechanism by which miR160 fine-tunes auxin signaling in plants.

The Loess Plateau region of northwestern China has unique geological and dry/semi-dry climate characteristics. However, knowledge about ectomycorrhizal fungal (EMF) communities in the Loess Plateau is limited. In this study, we investigated EMF communities in Populus simonii and Pinus tabuliformis patches within the forest-steppe zone, in pine forests within the forest zone and the transitional zone between them. We revealed high species richness (115 operational taxonomic units [OTUs]) of indigenous EMF resources at the Loess Plateau, of which Tomentella (35 OTUs), Inocybe (16), Sebacina (16) and Geopora (7) were the most OTU-rich lineages. EMF richness within the forest-steppe zone and the transitional zone was limited, while the natural pine forest maintained diverse EMF communities in the forest zone. The changes of EMF community richness and composition along arid eco-zones were highlighted for the complex factors including precipitation, soil factors, host, DBH and altitude. Indicator analysis revealed that some EMF showed clear host preference and some taxa, i.e., genera Geopora and Inocybe, were dominant in drought and alkaline-saline conditions attributed to their environmental preference. This study revealed that EMF communities were quite limited in the forest-steppe zone, while the forest region contained diverse EMF communities in the Loess Plateau.

Shiga toxin 2 (Stx2) is a major virulence factor in infections with Stx-producing Escherichia coli (STEC), which can cause serious clinical complications in humans, such as hemolytic uremic syndrome (HUS). Recently, we screened and identified two peptide-based Stx2 neutralizers, TF-1 and WA-8, which specifically and directly bind to Stx2. Computer simulations suggested that the majority of TF-1 or WA-8 binds tightly at the receptor-binding site 3 of Stx2. The two peptides also effectively inhibited the cytotoxic activity of Stx2 by blocking the binding of Stx2 to target cells. TF-1 exhibits remarkable therapeutic potency in both mice and rat toxicity models. In mice toxicity models, TF-1 provided full protection when mice were injected with 5 LD50 of Stx2. In rat toxicity models, TF-1 reduced fatal tissue damage and completely protected rats from the lethal challenges of Stx2. In these rats, TF-1 significantly decreased the concentration of Stx2 in blood and diminished tissue distribution levels of Stx2. Furthermore, TF-1 effectively protected rats from the pathological effects caused by Stx2, especially in the kidney, thymus, adrenal gland, and lung. Taken together, these results indicate that TF-1 is a promising therapeutic agent against the pathogenicity of Stx2.

Genome editing via CRISPR/Cas9 has become an efficient and reliable way to make precise, targeted changes to the genome of living cells. CXCR4 is a co-receptor for the human immunodeficiency virus type 1 (HIV-1) infection and has been considered as an important therapeutic target for AIDS. CXCR4 mediates viral entry into human CD4+ cells by binding to envelope protein, gp120. Here, we show that human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing, leading to HIV-1 resistance of human primary CD4+ T cells. We also show that the Cas9-mediated ablation of CXCR4 demonstrated high specificity and negligible off-target effects without affecting cell division and propagation. The precise and efficient genome editing of CXCR4 will provide a new strategy for therapeutic application against HIV-1 infection.

Degeneration of midbrain dopaminergic (DA) neurons is a key pathological event of Parkinson’s disease (PD). Limited adult dopaminergic neurogenesis has led to novel therapeutic strategies such as transplantation of dopaminergic precursors (DPs). However, this strategy is currently restrained by a lack of cell source, the tendency for the DPs to become a glial-restricted state and the tumor formation after transplantation. Here, we demonstrate the direct conversion of mouse fibroblasts into induced DPs (iDPs) by ectopic expression of Brn2, Sox2 and Foxa2. Besides expression with neural progenitor markers and midbrain genes including Corin, Otx2 and Lmx1a, the iDPs were restricted to dopaminergic neuronal lineage upon differentiation. After transplantation into MPTP-lesioned mice, iDPs differentiated into DA neurons, functionally alleviated the motor deficits and reduced the loss of striatal DA neuronal axonal termini. Importantly, no iDPs-derived astroctyes and neoplasia were detected in mouse brains after transplantation. We propose that the iDPs from direct reprogramming provides a safe and efficient cell source for PD treatment.

Most plant viruses that seriously damage agricultural crops are transmitted by insects. However, the mechanisms enabling virus transmission by insect vectors are poorly understood. The brown planthopper (Nilaparvata lugens) is one of the most serious rice pests, causing extensive damage to rice plants by sucking the phloem sap and transmitting viruses, including Rice ragged stunt virus (RRSV). In this study, we investigated the mechanisms of RRSV transmission from its insect vector to the rice plant in vivo using the terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and RNA interference technology. RRSV induced apoptosis in the salivary gland cells of its insect vector, N. lugens. The RRSV-induced apoptosis was regulated through a caspase-dependent manner and inhibition of the expression of N. lugens caspase-1 genes significantly interfered with virus transmission. Our findings establish a link between virus-associated apoptosis and virus transmission from the insect vector to the host plant.

The cluster of differentiation 24 (CD24) Ala57Val polymorphism has been implicated as a risk factor for multiple sclerosis (MS) and systemic lupus erythematosus (SLE); however, genetic studies have produced controversial results. A meta-analysis was performed on this topic. We used odds ratio (OR) and 95% confidence interval (95% CI) to investigate the strength of association. Eleven studies from nine publications consisting of 2466 cases and 2650 controls were included. The results suggested that the CD24 Val/Val genotypes were associated with an increased risk of MS in all study subjects and Caucasians (OR = 2.28, 95% CI: 1.68–3.10, Pz < 0.001 and OR = 2.30, 95% CI: 1.66–3.20, Pz < 0.001, respectively). Sensitivity analysis showed that no individual study was found to be significantly biasing the pooled results. Although meta-analysis also suggested an association between the CD24 Val/Val genotypes and SLE risk in Caucasians (OR = 1.71, 95% CI: 1.31–2.24, Pz < 0.001), sensitivity analysis demonstrated that the association was not statistically significant after removing a Spanish study. In conclusion, this meta-analysis suggests that the CD24 Ala57Val polymorphism is associated with an increased risk of MS in Caucasians. However, the available evidence is not sufficient to support an association between the CD24 Ala57Val polymorphism and SLE risk.

Membrane fouling remains an obstacle to wide-spread applications of membrane bioreactors (MBRs) for wastewater treatment and reclamation. Herein, we report a simple method to prepare a composite conductive microfiltration (MF) membrane by introducing a stainless steel mesh into a polymeric MF membrane and to effectively control its fouling by applying an external electric field. Linear sweep voltammetry and electrochemical impedance spectroscopy analyses showed that this conductive membrane had very good electrochemical properties. Batch tests demonstrated its anti-fouling ability in filtration of bovine serum albumin, sodium alginate, humic acid and silicon dioxide particles as model foulants. The fouling rate in continuous-flow MBRs treating wastewater was also decreased by about 50% for this conductive membrane with 2 V/cm electric field compared to the control test during long-term operation. The enhanced electrostatic repulsive force between foulants and membrane, in-situ cleaning by H2O2 generated from oxygen reduction and decreased production of soluble microbial products and extracellular polymeric substances contributed to fouling mitigation in this MBR. The results of this study shed light on the control strategy of membrane fouling for achieving a sustainable operation of MBRs.

WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription; however, its role in bladder cancer remains largely unknown. Our study investigated the role of WDR5 in bladder cancer and demonstrated that WDR5 was upregulated in bladder cancer tissues and elevated WDR5 protein levels positively correlated with advanced tumor stage and poor survival. Through gain or loss of function, we demonstrated that WDR5 promoted proliferation, self-renewal and chemoresistance to cisplatin in bladder cancer cells in vitro and tumor growth in vivo. Mechanistically, WDR5 regulated various functions in bladder cancer by mediating the transcription of cyclin B1, cyclin E1, cyclin E2, UHMK1, MCL1, BIRC3 and Nanog by histone H3 lysine 4 trimethylation. Therefore, we have discovered that WDR5 plays an important role in bladder cancer suggesting that WDR5 is a potential biomarker and a promising target in the treatment of bladder cancer.

Autophagy, referring to an evolutionarily conserved, multi-step lysosomal degradation process, has been well-known to be initiated by Unc-51 like kinase 1 (ULK1) with some links to Parkinson’s disease (PD). MicroRNAs (miRNAs), small and non-coding endogenous RNAs 22 ~ 24 nucleotides (nt) in length, have been demonstrated to play an essential role for modulating autophagy. Recently, the relationships between miRNAs and autophagy have been widely reported in PD; however, how microRNAs regulate autophagy still remains in its infancy. Thus, in this study, we computationally constructed the ULK1-regulated autophagic kinase subnetwork in PD and further identified ULK1 able to negatively regulate p70S6K in starvation-induced autophagy of neuroblastoma SH-SY5Y cells. Combination of in silico prediction and microarray analyses, we identified that miR-4487 and miR-595 could target ULK1 and experimentally verified they could negatively or positively regulate ULK1-mediated autophagy. In conclusion, these results may uncover the novel ULK1-p70S6K autophagic pathway, as well as miR-4487 and miR-595 as new ULK1 target miRNAs. Thus, these findings would provide a clue to explore ULK1 and its target miRNAs as potential biomarkers in the future PD therapy.

Experimentally-determined or computationally-predicted protein phosphorylation sites for distinctive species are becoming increasingly common. In this paper, we compare the predictive performance of a novel classification algorithm with different encoding schemes to develop a rice-specific protein phosphorylation site predictor. Our results imply that the combination of Amino acid occurrence Frequency with Composition of K-Spaced Amino Acid Pairs (AF-CKSAAP) provides the best description of relevant sequence features that surround a phosphorylation site. A support vector machine (SVM) using AF-CKSAAP achieves the best performance in classifying rice protein phophorylation sites when compared to the other algorithms. We have used SVM with AF-CKSAAP to construct a rice-specific protein phosphorylation sites predictor, Rice_Phospho 1.0 (http://bioinformatics.fafu.edu.cn/rice_phospho1.0). We measure the Accuracy (ACC) and Matthews Correlation Coefficient (MCC) of Rice_Phospho 1.0 to be 82.0% and 0.64, significantly higher than those measures for other predictors such as Scansite, Musite, PlantPhos and PhosphoRice. Rice_Phospho 1.0 also successfully predicted the experimentally identified phosphorylation sites in LOC_Os03g51600.1, a protein sequence which did not appear in the training dataset. In summary, Rice_phospho 1.0 outputs reliable predictions of protein phosphorylation sites in rice and will serve as a useful tool to the community.

The interleukin-1 (IL-1) gene polymorphisms have been implicated in chronic obstructive pulmonary disease (COPD) risk, but results are controversial. We aimed to conduct a meta-analysis to address this issue. Odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of the association. The meta-analysis revealed no association between the IL1B (−511), (−31), (+3954) polymorphisms and COPD risk. However, stratification by ethnicity indicated that the T allele carriers of the IL1B (−511) polymorphism and the C allele carriers of the IL1B (−31) variant were associated with an increased risk for developing COPD in East Asians (OR = 1.61, 95% CI: 1.13–2.31, Pz = 0.009 and OR = 1.55, 95% CI: 1.14–2.11, Pz = 0.006, respectively). The meta-analysis revealed a significant association between the IL1RN (VNTR) polymorphism and COPD risk in all study subjects and East Asians under homozygote model (22 vs. LL: OR = 3.16, 95% CI: 1.23–8.13, Pz = 0.017 and OR = 3.20, 95% CI: 1.13–9.12, Pz = 0.029, respectively). Our meta-analysis suggests that the IL1B (−511), (−31) and IL1RN (VNTR) polymorphisms are associated with COPD risk in East Asians. There is no association between the IL1B (+3954) polymorphism and COPD risk. Further studies should be performed in other ethnic groups besides East Asians.