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MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference ( P <0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3′-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase–PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2′- O -methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo , and highlight the therapeutic potential of miR-375 in HCC treatment.

Background Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. Methods CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. Results CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/β-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. Conclusions CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.

Evidence of executive dysfunction in autism spectrum disorders (ASD) across development remains mixed and establishing its role is critical for guiding diagnosis and intervention. The primary objectives of this meta-analysis is to analyse executive function (EF) performance in ASD, the fractionation across EF subdomains, the clinical utility of EF measures and the influence of multiple moderators (for example, age, gender, diagnosis, measure characteristics). The Embase, Medline and PsychINFO databases were searched to identify peer-reviewed studies published since the inclusion of Autism in DSM-III (1980) up to end of June 2016 that compared EF in ASD with neurotypical controls. A random-effects model was used and moderators were tested using subgroup analysis. The primary outcome measure was Hedges' g effect size for EF and moderator factors. Clinical sensitivity was determined by the overlap percentage statistic (OL%). Results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 235 studies comprising 14 081 participants were included (N, ASD=6816, Control=7265). A moderate overall effect size for reduced EF (Hedges' g=0.48, 95% confidence interval (CI) 0.43-0.53) was found with similar effect sizes across each domain. The majority of moderator comparisons were not significant although the overall effect of executive dysfunction has gradually reduced since the introduction of ASD. Only a small number of EF measures achieved clinical sensitivity. This study confirms a broad executive dysfunction in ASD that is relatively stable across development. The fractionation of executive dysfunction into individual subdomains was not supported, nor was diagnostic sensitivity. Development of feasible EF measures focussing on clinical sensitivity for diagnosis and treatment studies should be a priority.

Background: An inverse association between alcoholic beverage intake and risk of renal cell cancer has been suggested in recent studies. Methods: We examined the association between alcoholic beverages and renal cell cancer risk in a meta-analysis. We identified relevant studies by searching the database of PubMed, EMBASE, and MEDLINE published through August 2011. We combined the study-specific relative risks (RRs) using a random-effects model. Results: A total of 20 case–control studies, 3 cohort studies, and 1 pooled analysis of cohort studies were included in the meta-analysis. We observed that alcoholic beverage intake was associated with a lower risk of renal cell cancer in combined analysis of case–control and cohort studies; for total alcoholic beverage intake, combined RRs (95% confidence intervals) comparing top with bottom categories were 0.76 (0.68–0.85) in case–control studies, and 0.71 (0.63–0.78) in cohort studies ( P for difference by study design=0.02). The inverse associations were observed for both men and women and for each specific type alcoholic beverage (beer, wine, and liquor). Also, we found that one drink per day of alcoholic beverage conferred the reduction in renal cell cancer risk, but further drinking above that level did not add benefit. Conclusion: The findings from our meta-analysis support the hypothesis that alcoholic beverage intake is inversely associated with a lower risk of renal cell cancer, with moderate consumption conferring the protection and higher consumption conferring no additional benefits.

Logical qubit encoding and quantum error correction (QEC) protocols have been experimentally demonstrated in various physical systems with multiple physical qubits, generally without reaching the break-even point, at which the lifetime of the quantum information exceeds that of the single best physical qubit within the logical qubit. Logical operations are challenging, owing to the necessary non-local operations at the physical level, making bosonic logical qubits that rely on higher Fock states of a single oscillator attractive, given their hardware efficiency. QEC that reaches the break-even point and single logical-qubit operations have been demonstrated using the bosonic cat code. Here, we experimentally demonstrate repetitive QEC approaching the break-even point of a single logical qubit encoded in a hybrid system consisting of a superconducting circuit and a bosonic cavity using a binomial bosonic code. This is achieved while simultaneously maintaining full control of the single logical qubit, including encoding, decoding and a high-fidelity universal quantum gate set with 97% average process fidelity. The corrected logical qubit has a lifetime 2.8 times longer than that of its uncorrected counterpart. We also perform a Ramsey experiment on the corrected logical qubit, reporting coherence twice as long as for the uncorrected case.Repeated error correction creates a logical qubit encoded in the hybrid state of a superconducting circuit and a bosonic cavity, which is shown to be fully controllable under a universal single-qubit gate set.

Universal quantum computation 1 is striking for its unprecedented capability in processing information, but its scalability is challenging in practice because of the inevitable environment noise. Although quantum error correction (QEC) techniques 2 – 8 have been developed to protect stored quantum information from leading orders of error, the noise-resilient processing of the QEC-protected quantum information is highly demanded but remains elusive 9 . Here, we demonstrate phase gate operations on a logical qubit encoded in a bosonic oscillator in an error-transparent (ET) manner. Inspired by refs. 10 , 11 , the ET gates are extended to the bosonic code and are able to tolerate errors on the logical qubit during gate operations, regardless of the random occurrence time of the error. With precisely designed gate Hamiltonians through photon-number-resolved a.c. Stark shifts, the ET condition is fulfilled experimentally. We verify that the ET gates outperform the non-ET gates with a substantial improvement of gate fidelity after an occurrence of the single-photon-loss error. Our ET gates in superconducting quantum circuits can be readily extended to multiple encoded qubits and a universal gate set is within reach, holding the potential for reliable quantum information processing. Error-transparent quantum gates that can tolerate certain error during the execution of quantum operations have been demonstrated. Substantial improvement of the gate fidelity sheds lights on large-scale universal quantum computation.

A 9-valent human papillomavirus-6/11/16/18/31/33/45/52/58 (9vHPV) vaccine extends coverage to 5 next most common oncogenic types (31/33/45/52/58) in cervical cancer versus quadrivalent HPV (qHPV) vaccine. We describe efficacy, immunogenicity, and safety in Asian participants (India, Hong Kong, South Korea, Japan, Taiwan, and Thailand) from 2 international studies: a randomized, double-blinded, qHPV vaccine-controlled efficacy study (young women aged 16-26 years; NCT00543543; Study 001); and an immunogenicity study (girls and boys aged 9-15 years; NCT00943722; Study 002). Participants (N = 2519) were vaccinated at day 1 and months 2 and 6. Gynecological samples (Study 001 only) and serum were collected for HPV DNA and antibody assessments, respectively. Injection-site and systemic adverse events (AEs) were monitored. Data were analyzed by country and vaccination group. 9vHPV vaccine prevented HPV-31/33/45/52/58-related persistent infection with 90.4%-100% efficacy across included countries. At month 7, ≥97.9% of participants seroconverted for each HPV type. Injection-site AEs occurred in 77.7%-83.1% and 81.9%-87.5% of qHPV and 9vHPV vaccine recipients in Study 001, respectively, and 62.4%-85.7% of girls/boys in Study 002; most were mild to moderate. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Asian participants. Data support 9vHPV vaccination programs in Asia. NCT00543543; NCT00943722.

Volatile organic compounds (VOCs) are secondary pollutant precursors having adverse impacts on the environment and human health. Although VOC emissions, their sources, and impacts have been investigated, the focus has been on large-scale industrial sources or indoor environments; studies on relatively small-scale enterprises (e.g., auto-repair workshops) are lacking. Here, we performed field VOC measurements for an auto-repair painting facility in Korea and analyzed the characteristics of VOCs emitted from the main painting workshop (top coat). The total VOC concentration was 5069–8058 ppb, and 24–35 species were detected. The VOCs were mainly identified as butyl acetate, toluene, ethylbenzene, and xylene compounds. VOC characteristics differed depending on the paint type. Butyl acetate had the highest concentration in both water- and oil-based paints; however, its concentration and proportion were higher in the former (3256 ppb, 65.5%) than in the latter (2449 ppb, 31.1%). Comparing VOC concentration before and after passing through adsorption systems, concentrations of most VOCs were lower at the outlets than the inlets of the adsorption systems, but were found to be high at the outlets in some workshops. These results provide a theoretical basis for developing effective VOC control systems and managing VOC emissions from auto-repair painting workshops.

Thermal management through personal heating and cooling is a strategy by which to expand indoor temperature setpoint range for large energy saving. We show that nanoporous polyethylene (nanoPE) is transparent to mid-infrared human body radiation but opaque to visible light because of the pore size distribution (50 to 1000 nanometers). We processed the material to develop a textile that promotes effective radiative cooling while still having sufficient air permeability, water-wicking rate, and mechanical strength for wearability. We developed a device to simulate skin temperature that shows temperatures 2.7° and 2.0°C lower when covered with nanoPE cloth and with processed nanoPE cloth, respectively, than when covered with cotton. Our processed nanoPE is an effective and scalable textile for personal thermal management.