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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.

A large qubit capacity and an individual readout capability are two crucial requirements for large-scale quantum computing and simulation 1 . As one of the leading physical platforms for quantum information processing, the ion trap has achieved a quantum simulation of tens of ions with site-resolved readout in a one-dimensional Paul trap 2 – 4 and of hundreds of ions with global observables in a two-dimensional (2D) Penning trap 5 , 6 . However, integrating these two features into a single system is still very challenging. Here we report the stable trapping of 512 ions in a 2D Wigner crystal and the sideband cooling of their transverse motion. We demonstrate the quantum simulation of long-range quantum Ising models with tunable coupling strengths and patterns, with or without frustration, using 300 ions. Enabled by the site resolution in the single-shot measurement, we observe rich spatial correlation patterns in the quasi-adiabatically prepared ground states, which allows us to verify quantum simulation results by comparing the measured two-spin correlations with the calculated collective phonon modes and with classical simulated annealing. We further probe the quench dynamics of the Ising model in a transverse field to demonstrate quantum sampling tasks. Our work paves the way for simulating classically intractable quantum dynamics and for running noisy intermediate-scale quantum algorithms 7 , 8 using 2D ion trap quantum simulators. In this work, stable trapping of a two-dimensional Wigner crystal of above 500 ions is achieved, and the quantum simulation of 300 ions with individual state detection demonstrated.

Summary Length–weight relationships are described for four marine teleost fish species caught in the South China Sea. A total of 625 individuals were collected from April to August 2007 and November 2012 using a bottom trawl (mesh size, 3.9 cm) and longline fishing. The values of parameters a and b ranged from 0.004612 to 0.02137 and 3.019 to 3.371, respectively. The high r2 values (all >.950) indicate that these relationships are robust and will be appropriate for use in fisheries management of these species.

Summary The length–weight relationships were determined for three fish species: Histiopterus typus (Temminck & Schlegel, 1844), Branchiostegus argentatus (Cuvier, 1830), and Ilisha elongata (Anonymous [Bennett], 1830). Samples were collected from the South China Sea with commercial trawls in June 2016 using trawl nets. Prior to this study the length–weight relationships for these three species were unknown.

Background The recently described heavy-chain deposition disease (HCDD) is a comparatively rare monoclonal immunoglobulin disorder characterized histopathologically by glomerular and tubular basement membrane deposition of nonamyloidotic monoclonal heavy chains without associated light chains.Method We have described a case of γ2-HCDD presenting with proteinuria, microhematuria, severe hypertension, and rapidly progressive renal failure, which serum creatinine level was only 1.52 mg/dL in early stage HCDD, and the clinicopathologic features of this case have been compared with other reported cases of γ2-HCDD.ResultsRenal biopsy disclosed nodular sclerosing glomerulopathy. Immunofluorescence analysis revealed IgG2 (2+) heavy chain and C3 (+) in the mesangium and along the capillary walls and tubular basement membranes without IgA, IgM, κ and λ light chains. Electron microscopy revealed electron-dense deposits along the glomerular and tubular basement membranes as well as in the mesangium. Moreover, regardless of therapy, the condition of the patient progressively deteriorated, with less than 3 months of renal survival.ConclusionRapid progressive renal failure was a common feature in both cases of γ2-HCDD. We propose that a possible link exists between prognosis of renal HCDD and the subclass of heavy chain deposited in the kidney.

Purpose: The mechanism of lung cancer (LC) in male patients with chronic obstructive pulmonary disease (COPD) has not been well understood, and the early diagnosis is currently challenging. The study aimed to explore the association of DNA methylation levels with LC development in male COPD patients. Patients and Methods: A total of 147 male participants were divided into four groups, ie, COPD+LC group, COPD group, LC group, and control (CON) group. The methylation levels of human serine protease inhibitor A1 (SERPINA1) and the serum levels of inflammatory biomarkers were compared among groups. Multivariate logistic regression was performed to explore the correlation of inflammatory biomarkers and gene methylation with lung cancer combining COPD. Results: SERPINA1 methylation levels were significantly higher in the COPD+LC group than that in the COPD group and LC group, respectively (all p < 0.05). The serum levels of interleukin (IL)-1[beta], IL-17, and transforming growth factor (TGF)- [beta]1 were significantly higher in the COPD+LC group than in the LC group (all p < 0.05). The SERPINA1 methylation levels were positively correlated with the IL-1[beta] levels (r = 0.5188,p = 0.0012). The AUC (area under curve) of SERPINA1 methylation for the diagnosis of LC in COPD was 0.677 (sensitivity of 52.2% and specificity of 78.2%). Conclusion: The methylation of SERPINA1 is linked to LC in patients with COPD. The SERPINA1 methylation levels were positively correlated with the IL-1[beta] levels. These findings may be of diagnostic value. Keywords: SERPINA1 methylation, lung squamous cell carcinoma, chronic obstructive pulmonary disease, male

Respiratory viruses including respiratory syncytial virus (RSV) contribute to exacerbations in COPD patients by inducing airway epithelial cell (AEC) damage and death and inciting inflammation. Methods: Differentiated air-liquid interface (ALI) cultures of primary AEC isolated from bronchial brushings of control subjects and COPD patients were cultured for 21 days and treated apically with OLO followed by RSV infection.

This paper reports on our observing campaign of faint satellites performed at the National Time Service Center and Sheshan station of SHAO from 1994 up to today. In the past few years due to benefit from using a large size CCD and the publication of the modern catalogues (UCAC2), a series of observations of faint satellites were obtained by us. Moreover the work of improving the orbit of Phoebe via numerical fit to the observations over a century is also presented.

The polynomial-fit method is applied to remove the uneven background of a satellite when it is near a bright primary object. Detailed analysis of this method is given. Some useful conclusions are drawn from the results of simulated data.

Whether the severity of obstructive sleep apnea (OSA) contributes to clinical polycythemia is uncertain, especially in young adults. This study aimed to assess the correlation between untreated OSA and polycythemia, controlling for multiple confounders, and to observe the difference in both genders. All participants underwent nocturnal polysomnography. Medical comorbidities, and demographic and laboratory information were also recorded. The relationship between OSA and concomitant polycythemia in both genders was analyzed. A total of 605 young participants (383 men and 222 women), aged 30.52 ± 7.21 years, were enrolled, with an average body mass index of 32.48 ± 6.06 kg/m . Although 74.4% of patients were diagnosed with OSA, less than 10% had polycythemia. The levels of hemoglobin and hematocrit increased with the severity of OSA; only men with severe OSA had significantly higher hemoglobin, hematocrit, and polycythemia compared with those in the control group ( < 0.01). Hemoglobin and hematocrit significantly correlated with mean pulse oxygen saturation (SpO ) ( < 0.001), but the correlation coefficients were weaker in women than in men. In logistic regression analysis, mean SpO , but not the apnea-hypopnea index (AHI), was found to be an independent predictor of polycythemia ( < 0.05). Areas under the receive operator characteristic analysis revealed that the cutoff values of hemoglobin and hematocrit were 155.5g/L and 44.6% ( < 0.001), respectively, for assessing nocturnal hypoxemia in men with OSA. Nocturnal mean SpO was an independent predictor of polycythemia in young adults. Mean SpO , compared with the AHI, was more associated with polycythemia. Men were more prone to suffer from polycythemia compared with women. Hemoglobin and hematocrit values might have diagnostic utility for assessing nocturnal hypoxia severity of OSA patients, especially in men.