The poor prognosis of ovarian cancer is mainly due to metastasis, and the specific mechanism underlying ovarian cancer metastasis is not clear. Ascites-derived exosomes (ADEs) play an important role ...in the progression of ovarian cancer, but the mechanism is unknown. Here, we found that ADEs promoted ovarian cancer metastasis not only in vitro but also in vivo. This promotive function was based on epithelial-mesenchymal transition (EMT) of ovarian cancer cells. Bioinformatics analysis of RNA sequencing microarray data indicated that miR-6780b-5p may be the key microRNA (miRNA) in ADEs that facilitates cancer metastasis. Moreover, the expression of exosomal miR-6780b-5p correlated with tumor metastasis in ovarian cancer patients. miR-6780b-5p overexpression promoted and miR-6780b-5p downregulation suppressed EMT of ovarian cancer cells. These results suggest that ADEs transfer miR-6780b-5p to ovarian cancer cells, promoting EMT and finally facilitating ovarian cancer metastasis.
OBJECTIVE—Vascular precursor cells with angiogenic potentials are important for tissue repair, which is impaired in diabetes mellitus. MicroRNAs are recently discovered key regulators of gene ...expression, but their role in vascular precursor cell–mediated angiogenesis in diabetes mellitus is unknown. We tested the hypothesis that the microRNA miR-27b rescues impaired bone marrow–derived angiogenic cell (BMAC) function in vitro and in vivo in type 2 diabetic mice.
APPROACH AND RESULTS—BMACs from adult male type 2 diabetic db/db and from normal littermate db/+ mice were used. miR-27b expression was decreased in db/db BMACs. miR-27b mimic improved db/db BMAC function, including proliferation, adhesion, tube formation, and delayed apoptosis, but it did not affect migration. Elevated thrombospondin-1 (TSP-1) protein in db/db BMACs was suppressed on miR-27b mimic transfection. Inhibition of miR-27b in db/+ BMACs reduced angiogenesis, which was reversed by TSP-1 small interfering RNA (siRNA). miR-27b suppressed the pro-oxidant protein p66 and mitochondrial oxidative stress, contributing to its protection of BMAC function. miR-27b also suppressed semaphorin 6A to improve BMAC function in diabetes mellitus. Luciferase binding assay suggested that miR-27b directly targeted TSP-1, TSP-2, p66, and semaphorin 6A. miR-27b improved topical cell therapy of diabetic BMACs on diabetic skin wound closure, with a concomitant augmentation of wound perfusion and capillary formation. Normal BMAC therapy with miR-27b inhibition demonstrated reduced efficacy in wound closure, perfusion, and capillary formation. Local miR-27b delivery partly improved wound healing in diabetic mice.
CONCLUSIONS—miR-27b rescues impaired BMAC angiogenesis via TSP-1 suppression, semaphorin 6A expression, and p66shc-dependent mitochondrial oxidative stress and improves BMAC therapy in wound healing in type 2 diabetic mice.
The ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly on a global scale. Although it is clear that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted ...through human respiratory droplets and direct contact, the potential for aerosol transmission is poorly understood
. Here we investigated the aerodynamic nature of SARS-CoV-2 by measuring viral RNA in aerosols in different areas of two Wuhan hospitals during the outbreak of COVID-19 in February and March 2020. The concentration of SARS-CoV-2 RNA in aerosols that was detected in isolation wards and ventilated patient rooms was very low, but it was higher in the toilet areas used by the patients. Levels of airborne SARS-CoV-2 RNA in the most public areas was undetectable, except in two areas that were prone to crowding; this increase was possibly due to individuals infected with SARS-CoV-2 in the crowd. We found that some medical staff areas initially had high concentrations of viral RNA with aerosol size distributions that showed peaks in the submicrometre and/or supermicrometre regions; however, these levels were reduced to undetectable levels after implementation of rigorous sanitization procedures. Although we have not established the infectivity of the virus detected in these hospital areas, we propose that SARS-CoV-2 may have the potential to be transmitted through aerosols. Our results indicate that room ventilation, open space, sanitization of protective apparel, and proper use and disinfection of toilet areas can effectively limit the concentration of SARS-CoV-2 RNA in aerosols. Future work should explore the infectivity of aerosolized virus.
This study examines the effect of experience and knowledge on weather insurance adoption. First, we conduct insurance games with farmers, and find that the treatment improves real insurance take-up ...by 46%. The effect is not driven by changes in risk attitudes and perceived probability of disasters, or by learning of insurance benefits, but is driven by the experience acquired in the game. Second, we find that providing information about the payout probability has a strong positive effect on insurance take-up. Finally, when subjects receive both treatments, the probability information has a greater impact on take-up than does the disaster experience.
Our goal was to evaluate the survival disparities among the patients with T3N0-3M0 non-small-cell lung cancer with different T3 descriptors and to further externally validate the current T3 category.
...Overall survival and cancer-specific survival were compared using the Kaplan-Meier method with a log-rank test. A univariable and a multivariable Cox regression model were performed to determine the prognostic factors.
A series of 28,519 eligible cases was included. There were 17,971 cases with tumours that were larger than 5 cm but equal to or less than 7 cm (T-size group); 3,028 cases with tumours with chest wall/pericardium/phrenic nerve invasion (T-invasion group); 4,600 cases with tumours with additional tumour nodules in the same lobe (T-add group); and 2,900 cases with tumours that had at least 2 T3 descriptors (T-multiple group). The survival data indicated that patients in the T-add group had the best survival rates compared with other patients both in the entire cohort and in the subgroup analyses. Multivariable Cox models indicated that T3 descriptor was an important prognostic factor. Of the patients with different T3 descriptors, patients in the T-add group had the best prognosis, followed by patients in the T-size and in the T-invasion groups, and patients in the T-multiple group had the worst prognosis both in the pathological and clinical tumor-node-metastasis (TNM) stage cohorts.
Patients with T3N0-3M0 non-small-cell lung cancer with different T descriptors had inconsistent survival rates. T-add yielded the best survivals, followed by T-size and T-invasion, and T-multiple was associated with the worst survivals. Our results were exploratory in nature and need to be further validated.
Abstract Computer-assisted diagnosis is key for scaling up cervical cancer screening. However, current recognition algorithms perform poorly on whole slide image (WSI) analysis, fail to generalize ...for diverse staining and imaging, and show sub-optimal clinical-level verification. Here, we develop a progressive lesion cell recognition method combining low- and high-resolution WSIs to recommend lesion cells and a recurrent neural network-based WSI classification model to evaluate the lesion degree of WSIs. We train and validate our WSI analysis system on 3,545 patient-wise WSIs with 79,911 annotations from multiple hospitals and several imaging instruments. On multi-center independent test sets of 1,170 patient-wise WSIs, we achieve 93.5% Specificity and 95.1% Sensitivity for classifying slides, comparing favourably to the average performance of three independent cytopathologists, and obtain 88.5% true positive rate for highlighting the top 10 lesion cells on 447 positive slides. After deployment, our system recognizes a one giga-pixel WSI in about 1.5 min.
The ventral tegmental area (VTA) is well known for regulating reward consumption, learning, memory, and addiction behaviors through mediating dopamine (DA) release in downstream regions. Other than ...DA neurons, the VTA is known to be heterogeneous and contains other types of neurons, including glutamate neurons. In contrast to the well-studied and established functions of DA neurons, the role of VTA glutamate neurons is understudied, presumably due to their relatively small quantity and a lack of effective means to study them. Yet, emerging studies have begun to reveal the importance of glutamate release from VTA neurons in regulating diverse behavioral repertoire through a complex intra-VTA and long-range neuronal network. In this review, we summarize the features of VTA glutamate neurons from three perspectives, namely, cellular properties, neural connections, and behavioral functions. Delineation of VTA glutamatergic pathways and their interactions with VTA DA neurons in regulating behaviors may reveal previously unappreciated functions of the VTA in other physiological processes.
The authors explore the impact of a 2004 tax reform in China that reduced the value-added tax (VAT) on investment goods. Although the goal of the reform was to encourage upgrading of technology, ...results suggest there was no significant increase in fixed investment, new product introductions, or productivity. Rather, the authors find that firms shifted the composition of investment toward machinery and increased the capital intensity of production, which is consistent with a fall in the price of capital relative to labor. As a result, employment fell significantly in the treated provinces and sectors. Results are robust to a variety of approaches and suggest that the primary impact of the policy has been to induce labor-saving growth. In 2009, the VAT reform was extended to the rest of China.
The objective of this study was to quantify the relationship between vulnerability to cavitation and vessel diameter within a species. We measured vulnerability curves (VCs: percentage loss hydraulic ...conductivity versus tension) in aspen stems and measured vessel-size distributions. Measurements were done on seed-grown, 4-month-old aspen (Populus tremuloides Michx) grown in a greenhouse. VCs of stem segments were measured using a centrifuge technique and by a staining technique that allowed a VC to be constructed based on vessel diameter size-classes (D). Vessel-based VCs were also fitted to Weibull cumulative distribution functions (CDF), which provided best-fit values of Weibull CDF constants (c and b) and P₅₀ = the tension causing 50% loss of hydraulic conductivity. We show that P₅₀ = 6.166D⁻⁰.³¹³⁴ (R² = 0.995) and that b and 1/c are both linear functions of D with R² > 0.95. The results are discussed in terms of models of VCs based on vessel D size-classes and in terms of concepts such as the 'pit area hypothesis' and vessel pathway redundancy.
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