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Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions. Exosomal miR-23a directly suppressed its target prolyl hydroxylase 1 and 2 (PHD1 and 2), leading to the accumulation of hypoxia-inducible factor-1 α (HIF-1 α) in endothelial cells. Consequently, hypoxic lung cancer cells enhanced angiogenesis by exosomes derived from hypoxic cancer under both normoxic and hypoxic conditions. In addition, exosomal miR-23a also inhibits tight junction protein ZO-1, thereby increasing vascular permeability and cancer transendothelial migration. Inhibition of miR-23a by inhibitor administration decreased angiogenesis and tumour growth in a mouse model. Furthermore, elevated levels of circulating miR-23a are found in the sera of lung cancer patients, and miR-23a levels are positively correlated with proangiogenic activities. Taken together, our study reveals the clinical relevance and prognostic value of cancer-derived exosomal miR-23a under hypoxic conditions, and investigates a unique intercellular communication, mediated by cancer-derived exosomes, which modulates tumour vasculature.

Traffic emissions are a significant source of airborne particulate matter (PM) in ambient environments. These emissions contain an abundance of toxic metals and thus pose adverse effects on human health. Size-fractionated aerosol samples were collected from May to September 2013 by using micro-orifice uniform deposited impactors (MOUDIs). Sample collection was conducted simultaneously at the inlet and outlet sites of Hsuehshan Tunnel in northern Taiwan, which is the second-longest freeway tunnel (12.9 km) in Asia. This endeavor aims to characterize the chemical constituents and size distributions, as well as fingerprinting ratios of particulate metals emitted by vehicle fleets. A total of 36 metals in size-resolved aerosols were determined through inductively coupled plasma mass spectrometry. Three major groups – namely, tailpipe emissions (Zn, Pb, and V in fine mode), wear debris (Cu, Cd, Fe, Ga, Mn, Mo, Sb, and Sn), and resuspended dust (Ca, Mg, K, and Rb) – of airborne PM metals were categorized on the basis of the results of enrichment factor, correlation matrix, and principal component analysis. Size distributions of wear-originated metals resembled the pattern of crustal elements, which were predominated by super-micron particulates (PM1–10). By contrast, tailpipe exhaust elements such as Zn, Pb, and V were distributed mainly in submicron particles. By employing Cu as a tracer of wear abrasion, several inter-metal ratios – including Fe / Cu (14), Ba / Cu (1.05), Sb / Cu (0.16), Sn / Cu (0.10), and Ga / Cu (0.03) – served as fingerprints for wear debris. However, the data set collected in this work is useful for further studies on traffic emission inventory and human health effects of traffic-related PM.

Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial–mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo . These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.

In the tumor microenvironment, chemokine system has a critical role in tumorigenesis and metastasis. The acquisition of stem-like properties by cancer cells is involved in metastasis and drug resistance, which are pivotal problems that result in poor outcomes in patients with lung cancer. Patients with advanced lung cancer present high plasma levels of transforming growth factor-β1 (TGFβ1), which correlate with poor prognostic features. Therefore, TGFβ1 may be important in the tumor microenvironment, where chemokines are widely expressed. However, the role of chemokines in TGFβ1-induced tumor progression still remains unclear. In our study, TGFβ1 upregulated CXC chemokine receptor expression, migration, invasion, epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) formation in lung adenocarcinoma. We found that CXCR7 was the most upregulated chemokine receptor induced by TGFβ1. CXCR7 knockdown resulted in reduction of migration, invasion and EMT induced by TGFβ1, whereas CXCR4 knockdown did not reverse TGFβ1-promoted EMT. CXCR7 silencing significantly decreased cancer sphere-forming capacity, stem-like properties, chemoresistance and TGFβ1-induced CSC tumor initiation in vivo . In clinical samples, high TGFβ1 and CXCR7 expression was significantly associated with the late stages of lung adenocarcinoma. Moreover, TGFβ1 and CXCR7 coexpression was positively correlated with the CSC marker, CD44, which is associated with lymph node metastasis. Besides, patients with high expression of both CXCR7 and TGFβ1 presented a significantly worse survival rate. These results suggest that the TGFβ1-CXCR7 axis may be a prognostic marker and may provide novel targets for combinational therapies to be used in the treatment of advanced lung cancer in the future.

We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser 473 and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and co-expression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.

Inflammatory bowel disease is a global disease in the 21st century. We aimed to assess the changing incidence and prevalence of inflammatory bowel disease around the world. We searched MEDLINE and Embase up to and including Dec 31, 2016, to identify observational, population-based studies reporting the incidence or prevalence of Crohn's disease or ulcerative colitis from 1990 or later. A study was regarded as population-based if it involved all residents within a specific area and the patients were representative of that area. To be included in the systematic review, ulcerative colitis and Crohn's disease needed to be reported separately. Studies that did not report original data and studies that reported only the incidence or prevalence of paediatric-onset inflammatory bowel disease (diagnosis at age <16 years) were excluded. We created choropleth maps for the incidence (119 studies) and prevalence (69 studies) of Crohn's disease and ulcerative colitis. We used temporal trend analyses to report changes as an annual percentage change (APC) with 95% CI. We identified 147 studies that were eligible for final inclusion in the systematic review, including 119 studies of incidence and 69 studies of prevalence. The highest reported prevalence values were in Europe (ulcerative colitis 505 per 100 000 in Norway; Crohn's disease 322 per 100 000 in Germany) and North America (ulcerative colitis 286 per 100 000 in the USA; Crohn's disease 319 per 100 000 in Canada). The prevalence of inflammatory bowel disease exceeded 0·3% in North America, Oceania, and many countries in Europe. Overall, 16 (72·7%) of 22 studies on Crohn's disease and 15 (83·3%) of 18 studies on ulcerative colitis reported stable or decreasing incidence of inflammatory bowel disease in North America and Europe. Since 1990, incidence has been rising in newly industrialised countries in Africa, Asia, and South America, including Brazil (APC for Crohn's disease +11·1% [95% CI 4·8–17·8] and APC for ulcerative colitis +14·9% [10·4–19·6]) and Taiwan (APC for Crohn's disease +4·0% [1·0–7·1] and APC for ulcerative colitis +4·8% [1·8–8·0]). At the turn of the 21st century, inflammatory bowel disease has become a global disease with accelerating incidence in newly industrialised countries whose societies have become more westernised. Although incidence is stabilising in western countries, burden remains high as prevalence surpasses 0·3%. These data highlight the need for research into prevention of inflammatory bowel disease and innovations in health-care systems to manage this complex and costly disease. None.

In this work, novel WNbMoTaVZr x ( x  = 0.1, 0.25, 0.5, 0.75, 1.0) refractory high entropy alloys (RHEAs) were developed, and the corresponding phase formation, microstructure and mechanical properties were investigated. As compared with the WNbMoTa and WNbMoTaV derivative alloys, the present WNbMoTaVZr x RHEAs demonstrated significantly improved strength and hardness, especially the specific yield strength. The increase of the strength was attributed to the solid solution strengthening effect, resulting from the severe lattice distortion associated with lager-atomic-sized Zr element. With the increase of Zr content, the microstructure changed from grain morphology to dendritic structures. The formation of the second phase with the increase of Zr content was also observed, and its effects on the strengthening, plastic deformation and fracture behaviors were discussed. The deformation-evolution investigations have shown that under applied loadings, microcracks initiated at interdendritic regions with relatively soft second phase. The phase thermostability analysis suggests that the phase structure of typical WNbMoTaVZr x RHEAs could be stable at elevated temperature. Graphical abstract

The role of N 6 -methyladenosine (m 6 A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m 6 A methylases and increases m 6 A levels in gastric epithelial cells. Reducing m 6 A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m 6 A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m 6 A-regulated target during H. pylori infection. m 6 A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1 , reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m 6 A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion. N 6 -methyladenosine (m 6 A) modification of mRNA regulates gene expression in eukaryotes. Here, Zeng et al. show that m 6 A modification of mRNAs contributes to protection against the pathogen Helicobacter pylori by downregulating a host protein that acts as receptor for the pathogen.

Braille system is widely used worldwide for communication by visually impaired people. However, there are still some visually impaired people who are unable to learn Braille system due to various factors, such as the age (too young or too old), brain damage, etc. A wearable and low-cost Braille recognition system may substantially help these people recognize Braille or assist them in Braille learning. In this work, we fabricated polydimethylsiloxane (PDMS)-based flexible pressure sensors to construct an electronic skin (E-skin) for the application of Braille recognition. The E-skin mimics human touch sensing function for collecting Braille information. Braille recognition is realized with a neural network based on memristors. We utilize a binary neural network algorithm with only two bias layers and three fully connected layers. Such neural network design remarkably reduces the calculation burden and, thus, the system cost. Experiments show that the system can achieve a recognition accuracy of up to 91.25%. This work demonstrates the possibility of realizing a wearable and low-cost Braille recognition system and a Braille learning-assistance system.

Acupuncture and related therapies such as moxibustion and transcutaneous electrical nerve stimulation are often used to manage cancer-related symptoms, but their effectiveness and safety are controversial. We conducted this overview to summarise the evidence on acupuncture for palliative care of cancer. Our systematic review synthesised the results from clinical trials of patients with any type of cancer. The methodological quality of the 23 systematic reviews in this overview, assessed using the Methodological Quality of Systematic Reviews Instrument, was found to be satisfactory. There is evidence for the therapeutic effects of acupuncture for the management of cancer-related fatigue, chemotherapy-induced nausea and vomiting and leucopenia in patients with cancer. There is conflicting evidence regarding the treatment of cancer-related pain, hot flashes and hiccups and improving patients’ quality of life. The available evidence is currently insufficient to support or refute the potential of acupuncture and related therapies in the management of xerostomia, dyspnea and lymphedema and in the improvement of psychological well-being. No serious adverse effects were reported in any study. Because acupuncture appears to be relatively safe, it could be considered as a complementary form of palliative care for cancer, especially for clinical problems for which conventional care options are limited.