Biocompatibility of intraocular lens (IOL) is critical to vision reconstruction after cataract surgery. Foldable hydrophobic acrylic IOL is vulnerable to the adhesion of extracellular matrix proteins and cells, leading to increased incidence of postoperative inflammation and capsule opacification. To increase IOL biocompatibility, we synthesized a hydrophilic copolymer P(MPC-MAA) and grafted the copolymer onto the surface of IOL through air plasma treatment. X-ray photoelectron spectroscopy, atomic force microscopy and static water contact angle were used to characterize chemical changes, topography and hydrophilicity of the IOL surface, respectively. Quartz crystal microbalance with dissipation (QCM-D) showed that P(MPC-MAA) modified IOLs were resistant to protein adsorption. Moreover, P(MPC-MAA) modification inhibited adhesion and proliferation of lens epithelial cells (LECs) in vitro. To analyze uveal and capsular biocompatibility in vivo, we implanted the P(MPC-MAA) modified IOLs into rabbits after phacoemulsification. P(MPC-MAA) modification significantly reduced postoperative inflammation and anterior capsule opacification (ACO), and did not affect posterior capsule opacification (PCO). Collectively, our study suggests that surface modification by P(MPC-MAA) can significantly improve uveal and capsular biocompatibility of hydrophobic acrylic IOL, which could potentially benefit patients with blood-aqueous barrier damage.

Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.

The study aimed to identify the risk factors and frequency of hepatotoxicity in patients with advanced lung adenocarcinoma. Liver function tests were documented in 2108 patients with advanced (IIIB/IV) lung adenocarcinoma at a single institution who received first line platinum-based doublet chemotherapy. Hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Risk factors for hepatotoxicity were assessed using logistic regression analysis. Differences in hepatotoxicity between pemetrexed and non-pemetrexed regimens were evaluated after propensity score matching. After accounting for hepatic dysfunction during the first-line treatment, 892 patients receiving beyond first-line treatment were included in the subsequent analyses. Hepatotoxicity in beyond first-line treatment was compared between patients having epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy alone. In the first-line analysis, 316 (15.0%) patients developed liver dysfunction. Younger age (Odds Ratio [OR] 2.398, 95% Confidence Interval [95% CI] 1.755-3.275), pretreatment liver impairment (OR 2.285, 95% CI 1.622-3.220), and pemetrexed-contained chemotherapy (OR 1.835, 95% CI 1.408-2.393) were risk factors of hepatotoxicity (all P<0.001). Significant differences were observed for patients with all grades of hepatotoxicity while no differences were found concerning grade ¾ hepatotoxicity between 844 pemetrexed and 844 non-pemetrexed regimen matched cases (P<0.0001 and P=0.4220, respectively). After first-line treatment, the presence of hepatitis virus (OR 2.905, 95% CI 1.487-5.675; P=0.002) and TKI therapy (OR 2.621, 95% CI 1.809-3.798; P<0.001) were additionally associated with increased hepatotoxicity. Patients with advanced lung adenocarcinoma with younger age, pretreatment liver injury, and presence of hepatitis virus were at high risk for hepatotoxicity following chemotherapy. Pemetrexed-contained chemotherapy and TKIs should be used cautiously in patients who are susceptible to liver damage.

The role of GATA-binding protein 4 (GATA4) in neural crest cells (NCCs) is poorly defined. Here we showed that mouse NCCs lacking GATA4 exhibited developmental defects in craniofacial bone, teeth, and heart. The defects likely occurred due to decreased cell proliferation at the developmental stage. The in vitro results were consistent with the mouse model. The isobaric tags for relative and absolute quantitation assay revealed that BARX1 is one of the differentially expressed proteins after GATA4 knockdown in NCCs. On the basis of the results of dual-luciferase, electro-mobility shift, and chromatin immunoprecipitation assays, Barx1 expression is directly regulated by GATA4 in NCCs. In zebrafish, gata4 knockdown affects the development of NCCs derivatives. However, the phenotype in zebrafish could be partly rescued by co-injection of gata4 morpholino oligomers and barx1 mRNA. This study identified new downstream targets of GATA4 in NCCs and uncovered additional evidence of the complex regulatory functions of GATA4 in NCC development.

The present study aimed to investigate key long non-coding RNAs (lncRNAs) and genes, and to obtain insights into their roles in the progression of gallbladder cancer (GBC). The gene expression profile and non‑coding RNA profile of GSE62335, which included five separate GBC tissue samples and five matched adjacent gallbladder normal tissue samples, was downloaded from the Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNAs in the GBC tissues were identified, following which RNA binding protein analysis was performed using starBase v2.0 and the co‑expressed lncRNA‑mRNA pairs were predicted. Gene Ontology enrichment analysis for mRNAs was performed using the Database for Annotation Visualization and Integrated Discovery online tool. In addition, upstream microRNAs (miRNAs) were predicted for the co‑expressed lncRNAs and mRNAs. The results revealed that a total of 89 upregulated (13 lncRNAs and 76 mRNAs) and 261 downregulated transcripts (27 lncRNAs and 234 mRNAs) were identified in the GBC tissues. Only 9 lncRNAs had co‑expressed mRNAs, and lncRNA forkhead box P2 (FOXP2) was co‑expressed with the highest number of mRNAs, which were significant associated with the function of cell adhesion. In addition, the analysis of upstream miRNAs showed that FOXF1 adjacent non‑coding developmental regulatory RNA (FENDRR) had common upstream miRNAs, including miR‑18b‑5p, with another 119 differentially expressed genes, and that FENDRR was co‑expressed with adenomatosis polyposis coli downregulated 1 (APCDD1) and v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog (KIT). Taken together, the results suggested that the lncRNAs FOXP2 and FENDRR may be crucial in promoting the progression of GBC via cell adhesion and regulating miR‑18b‑5p, or through interactions with KIT and APCDD1, respectively.

The Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris recruits the hrp/T3SS system to inject pathogenicity effector proteins into host cells and uses the rpf/DSF cell-cell signaling system to regulate the expression of virulence factors such as extracellular enzymes and polysaccharide. Whether these two systems have any connection is unknown.

Beclin1 was previously found to be downregulated in human laryngeal cancer (LC) tissues, and it results in poor prognosis. This study aimed to further confirm the antitumor effects of Beclin1 in LC cell line Hep-2.

Dysregulation of long non-coding RNAs (LncRNAs) participated into the initiation and progression of different diseases via direct regulation of proteins or indirect regulation of microRNA (miRNA)-target genes. LINC00473 is a novel carcinoma-related LncRNA and up-regulated in many cancers for tumor growth and metastasis, but its role in chemotherapy resistance is unclear. We here investigated the function of LINC00473 in colorectal cancer (CRC) in vitro and in vivo The CRC tissues (n=20) and relative normal tissues were collected and found that LINC00473 was overexpressed in CRC tissues when compared with which in normal tissues. Highly expressed LINC00473 predicted large tumor size, high TNM stage of CRC patients. Interestingly, the tumor suppressor miR-15a was down-regulated and negatively correlated with LINC00473 levels in CRC. LINC00473 harbored the binding sites for miR-15a and reduced its availability in CRC cell line HCT116. Knockdown of LINC00473 elevated the expression of miR-15a. Moreover, in the Taxol-resistant HCT116, the LINC00473 level was further increased than that in HCT116. Knockdown of LINC00473 restored the Taxol-induced cytotoxicity, inhibited the cell vitality, colony formation and induced apoptosis, impaired the ability of migration or invasion, but these effects could be abrogated by the inhibition of miR-15a. Mechanistically, the BCL-2-related anti-apoptosis pathway was activated and the multidrug-resistant (MDR) genes LRP, MDR1 were up-regulated by LINC00473. Furthermore, inhibition of LINC00473 in vivo could overcome the Taxol resistance of CRC cells, could recover the expression of tumor suppressor miR-15a and chemotherapy-induced tumor regression, indicating that LINC00473 functioned as oncogene in CRC via miR-15a.

The black rot pathogen Xanthomonas campestris pv. campestris (Xcc) is a model organism for the study of plant bacterial pathogenesis mechanisms. In bacteria, σ factors serve as important regulatory elements that respond to various environmental signals and cues. Though Xcc encodes 15 putative σ factors little is known about their roles. As an approach to identify the potential role of each σ factor, we constructed mutations in each of the σ-factor genes as well as generating mutants deficient in multiple σ factors to assess these regulators potential additive functions. The work identified two σ70 factors essential for growth. Furthermore, the work discovered a third σ70 factor, RpoE1, important for virulence. Further studies revealed that RpoE1 positively regulates the expression of the hrp gene cluster that encodes the type III secretion system (T3SS) which determines the pathogenicity and hypersensitive response of Xcc on plants. In vivo and in vitro studies demonstrated that RpoE1 could bind to the promoter region and promote transcription of hrpX, a gene encoding a key regulator of the hrp genes. Overall, this systematic analysis reveals important roles in Xcc survival and virulence for previously uncharacterized σ70 factors that may become important targets for disease control.

Blast disease is one of the major rice diseases, and causes nearly 30% annual yield loss worldwide. Resistance genes that have been cloned, however, are effective only against specific strains. In cultivation practice, broad-spectrum resistance to various strains is highly valuable, and requires researchers to investigate the basal defense responses that are effective for diverse types of pathogens. In this study, we took a quantitative proteomic approach and identified 634 rice proteins responsive to infections by both Magnaporthe oryzae strains Guy11 and JS153. These two strains have distinct pathogenesis mechanisms. Therefore, the common responding proteins represent conserved basal defense to a broad spectrum of blast pathogens. Gene ontology analysis indicates that the “responding to stimulus” biological process is explicitly enriched, among which the proteins responding to oxidative stress and biotic stress are the most prominent. These analyses led to the discoveries of OsPRX59 and OsPRX62 that are robust callose inducers, and OsHSP81 that is capable of inducing both ROS production and callose deposition. The identified rice proteins and biological processes may represent a conserved rice innate immune machinery that is of great value for breeding broad-spectrum resistant rice in the future.

Warm needle acupuncture (WNA) is commonly used in primary osteoporosis (OP) management in China. The evidence of its effectiveness needs to be systematically reviewed.

The symptomatology of lupus nephritis (LN) consists of foamy urine and lower leg edema, as well as such systemic manifestations as oral ulcers, arthralgia/arthritis, and lymphadenopathy. However, these symptoms may appear mild and non-specific. If these symptoms are unrecognized, thus delaying treatment, approximately 10% of LN patients will develop permanent kidney damage and end-stage kidney disease. Therefore, the purpose of this study is to identify a surrogate biomarker for the early detection of LN. In this study, we first adopted next generation sequencing (NGS) in order to screen differential expression levels of microRNA between SLE patients with and without LN. The results of both the NGS and the literature review confirmed the potential of 15 microRNAs through real-time qPCR. We further considered clinical laboratory data for additional analysis. In total, 41 microRNAs demonstrated significant differences through NGS screening. We then verified eight microRNAs from NGS and seven microRNAs from the literature review using the real-time qPCR method in peripheral mononuclear cells. Ultimately, mir-125a-5p, miR-146a-5p, and mir-221-3p were found to be statistically significant not only in the screening study but also in the real-time qPCR verification studies. miR-146a-5p was observed to have a significant correlation with clinical biochemistry markers, as well as to be a surrogate biomarker for the early detection of lupus nephritis. This study is the first to show that the intracellular biomarker miR-146a-5p may serve as a useful specific biomarker for the detection of lupus nephritis among lupus patients in the future, regardless of serum albumin levels and spot urine protein/creatinine ratio.

MicroRNAs (miRNAs) are recognised as important regulators of a variety of fundamental biologic processes. Our study was undertaken to examine the role of MicroRNA-203 (miR-203) in modulating nitric oxide (NO) expression in female Sprague-Dawley rat mandibular condylar chondrocytes (MCCs) via targeting transient receptor potential vanilloid 4 (TRPV4) and to demonstrate the possible mechanism of NO inhibition by chondroprotective factor 17β-oestradiol (E2).

Although three-dimensional (3D) β-tricalcium phosphate (β-TCP) scaffolds serve as promising bone graft substitutes for the segmental bone defect treatment, no consensus has been achieved regarding their optimal 3D architecture.

Because lubricants may decrease trauma during coitus, it is hypothesized that they could aid in the prevention of HIV acquisition. Therefore, safety and anti-HIV-1 activity of over-the-counter (OTC) aqueous- (n = 10), lipid- (n = 2), and silicone-based (n = 2) products were tested. The rheological properties of the lipid-based lubricants precluded testing with the exception of explant safety testing. Six aqueous-based gels were hyperosmolar, two were nearly iso-osmolar, and two were hypo-osmolar. Evaluation of the panel of products showed Gynol II (a spermicidal gel containing 2% nonoxynol-9), KY Jelly, and Replens were toxic to Lactobacillus. Two nearly iso-osmolar aqueous- and both silicone-based gels were not toxic toward epithelial cell lines or ectocervical or colorectal explant tissues. Hyperosmolar lubricants demonstrated reduction of tissue viability and epithelial fracture/sloughing while the nearly iso-osmolar and silicon-based lubricants showed no significant changes in tissue viability or epithelial modifications. While most of the lubricants had no measurable anti-HIV-1 activity, three lubricants which retained cell viability did demonstrate modest anti-HIV-1 activity in vitro. To determine if this would result in protection of mucosal tissue or conversely determine if the epithelial damage associated with the hyperosmolar lubricants increased HIV-1 infection ex vivo, ectocervical tissue was exposed to selected lubricants and then challenged with HIV-1. None of the lubricants that had a moderate to high therapeutic index protected the mucosal tissue. These results show hyperosmolar lubricant gels were associated with cellular toxicity and epithelial damage while showing no anti-viral activity. The two iso-osmolar lubricants, Good Clean Love and PRÉ, and both silicone-based lubricants, Female Condom 2 lubricant and Wet Platinum, were the safest in our testing algorithm.

The goal for current orthopedic implant research is to design implants that have not only good biocompatibility but also antibacterial properties. TiO2 nanotubes (NTs) were fabricated on the titanium surface through electrochemical anodization, which added new properties, such as enhanced biocompatibility and potential utility as drug nanoreservoirs. The aim of the present study was to investigate the antibacterial properties and biocompatibility of NTs loaded with vancomycin (NT-V), both in vitro and in vivo. Staphylococcus aureus was used to study the antibacterial properties of the NT-V. There were three study groups: the commercially pure titanium (Cp-Ti) group, the NT group (nonloaded vancomycin), and the NT-V group. We compared NT-V biocompatibility and antibacterial efficacy with those of the NT and Cp-Ti groups. Compared with Cp-Ti, NT-V showed good antibacterial effect both in vitro and in vivo. Although the NTs reduced the surface bacterial adhesion in vitro, implant infection still developed in in vivo studies. Furthermore, the results also revealed that both NTs and NT-V showed good biocompatibility. Therefore, the NTs loaded with antibiotic might be potentially used for future orthopedic implants.

The U.S. Armed Forces offer educational and training benefits as incentives for service. This study investigates the influence of status configurations on military enlistment and their link to greater educational opportunity. Three statuses (socioeconomic status of origin, cognitive ability and academic performance) have particular relevance for life course options. We hypothesize that young men with inconsistent statuses are more likely to enlist than men with consistent status profiles, and that military service improves access to college for certain configurations. Analyses of the National Longitudinal Study of Adolescent Health (Add Health) show (1. that several status configurations markedly increased the likelihood of military enlistment and (2. within status configurations, recruits were generally more likely to enroll in higher education than nonveterans, with associate degrees being more likely.

Paired sense and antisense (S/AS) genes located in cis represent a structural feature common to the genomes of both prokaryotes and eukaryotes, and produce partially complementary transcripts. We used published genome and transcriptome sequence data and found that over 20% of genes (645 pairs) in the budding yeast Saccharomyces cerevisiae genome are arranged in convergent pairs with overlapping 3'-UTRs. Using published microarray transcriptome data from the standard laboratory strain of S. cerevisiae, our analysis revealed that expression levels of convergent pairs are significantly negatively correlated across a broad range of environments. This implies an important role for convergent genes in the regulation of gene expression, which may compensate for the absence of RNA-dependent mechanisms such as micro RNAs in budding yeast. We selected four representative convergent gene pairs and used expression assays in wild type yeast and its genetically modified strains to explore the underlying patterns of gene expression. Results showed that convergent genes are reciprocally regulated in yeast populations and in single cells, whereby an increase in expression of one gene produces a decrease in the expression of the other, and vice-versa. Time course analysis of the cell cycle illustrated the functional significance of this relationship for the three pairs with relevant functional roles. Furthermore, a series of genetic modifications revealed that the 3'-UTR sequence plays an essential causal role in mediating transcriptional interference, which requires neither the sequence of the open reading frame nor the translation of fully functional proteins. More importantly, transcriptional interference persisted even when one of the convergent genes was expressed ectopically (in trans) and therefore does not depend on the cis arrangement of convergent genes; we conclude that the mechanism of transcriptional interference cannot be explained by the transcriptional collision model, which postulates a clash between simultaneous transcriptional processes occurring on opposite DNA strands.

XB130 has been reported to be expressed by various types of cells such as thyroid cancer and esophageal cancer cells, and it promotes the proliferation and invasion of thyroid cancer cells. Our previous study demonstrated that XB130 is also expressed in gastric cancer (GC), and that its expression is associated with the prognosis, but the role of XB130 in GC has not been well characterized.

Over 200 cryptosporidiosis outbreaks have been reported, but little is known if other enteric pathogens were also involved in some of these outbreaks. Recently, an outbreak of cryptosporidiosis linked to poor hygiene by two Cryptosporidium hominis subtypes occurred in a pediatric hospital ward (Ward A) in China, lasting for more than 14 months. In this study, the concurrence during the outbreak of three other enteric pathogens with a similar transmission route, Giardia duodenalis, Enterocytozoon bieneusi, and Clostridium difficile, was assessed.