Testosterone deficiency is associated with poor prognosis among patients with chronic heart failure (HF). Physiological testosterone improves the exercise capacity of patients with HF. In this study, ...we evaluated whether treatment with physiological testosterone contributes to anti-fibrogenesis by modifying calcium homeostasis in cardiac fibroblasts and we studied the underlying mechanisms. Nitric oxide (NO) analyses, calcium (Ca2+) fluorescence, and Western blotting were performed in primary isolated rat cardiac fibroblasts with or without (control cells) testosterone (10, 100, 1,000 nmol/L) treatment for 48 hours. Physiological testosterone (10 nmol/L) increased NO production and phosphorylation at the inhibitory site of the inositol trisphosphate (IP3) receptor, thereby reducing Ca2+ entry, phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) expression, type I and type III pro-collagen production. Non-physiological testosterone-treated fibroblasts exhibited similar NO and collagen production capabilities as compared to control (testosterone deficient) fibroblasts. These effects were blocked by co-treatment with NO inhibitor (L-NG-nitro arginine methyl ester L-NAME, 100 μmol/L). In the presence of the IP3 receptor inhibitor (2-aminoethyl diphenylborinate 2-APB, 50 μmol/L), testosterone-deficient and physiological testosterone-treated fibroblasts exhibited similar phosphorylated CaMKII expression. When treated with 2-APB or CaMKII inhibitor (KN93, 10 μmol/L), testosterone-deficient and physiological testosterone-treated fibroblasts exhibited similar type I, and type III collagen production. In conclusion, physiological testosterone activates NO production, and attenuates the IP3 receptor/Ca2+ entry/CaMKII signaling pathway, thereby inhibiting the collagen production capability of cardiac fibroblasts.
This article addresses the challenges associated with hyperspectral image (HSI) reconstruction from miniaturized satellites, which often suffer from stripe effects and are computationally ...resource-limited. We propose a real-time compressed sensing (RTCS) network designed to be lightweight and require only relatively few training samples for efficient and robust HSI reconstruction in the presence of the stripe effect and under noisy transmission conditions. The RTCS network features a simplified architecture that reduces the required training samples and allows for easy implementation on integer-8-based encoders, facilitating rapid compressed sensing for stripe-like HSI, which exactly matches the moderate design of miniaturized satellites on push broom scanning mechanism. This contrasts optimization-based models that demand high-precision floating-point operations, making them difficult to deploy on edge devices. Our encoder employs an integer-8-compatible linear projection for stripe-like HSI data transmission, ensuring RTCS. Furthermore, based on the novel two-streamed architecture, an efficient HSI restoration decoder is proposed for the receiver side, allowing for edge-device reconstruction without needing a sophisticated central server. This is particularly crucial as an increasing number of miniaturized satellites necessitates significant computing resources on the ground station. Extensive experiments validate the superior performance of our approach, offering new and vital capabilities for existing miniaturized satellite systems.
Context‐aware ubiquitous learning (CAUL) technology provides language learners with interactive learning environments and has been found to increase learning effectiveness and self‐efficacy due to ...student interaction, discussion and evaluation of the entire learning process. This study used a mobile‐based ubiquitous learning system combined with a collaborative learning approach to develop Fitness‐specific English listening and reading, and fitness knowledge. The researchers recruited two groups of participants, an individual learning group (N = 31) and a collaborative learning group (N = 30), and evaluated their learning performance via pre‐and post‐tests. In addition, a questionnaire explored the perceived usefulness, usability, follow‐up intention of using the system and self‐efficacy regarding fitness‐specific English. The results show that both groups improved fitness‐specific English in terms of listening and reading comprehension. Moreover, collaborative learning was found to facilitate fitness‐specific knowledge, and those in the collaborative learning group improved their self‐efficacy more than those in the individual learning group.
Lay Description
What is already known about this topic
Computer assisted ubiquitous language learning (CAULL) can assist English learners in developing receptive language skills.
CAULL has been successfully applied in various authentic learning environments including university campuses, a fitness centre and a green technology building.
CAULL has been accepted by university undergraduates as an effective, interesting and motivating learning system.
What this paper adds
A Fitness‐based English ubiquitous learning (FBEUL) system was successfully adapted for collaborative learning.
Collaborative learning is as effective or more effective than individual learning for developing receptive English skills and subject (fitness‐based) knowledge.
The collaborative learning group improved their fitness‐based self‐efficacy significantly more than the individual learning group.
Implications for practice and/or policy
A collaborative learning approach can be successfully integrated into CAULL to cultivate ESP listening and reading comprehension, and subject‐specific knowledge.
Collaborative learning in a CAULL environment promotes student self‐efficacy which may result in better learning outcomes and increased autonomy.
System designers and ESP instructor can apply the CAULL system to other environments to motivate students and develop authentic language.
Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral
and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. ...However, the molecular pathway behind its effects on inflammation remains poorly understood. Since inflammatory cytokines such as TGFβ, TNFα, IL-1, IL-6, and IL-8 activate transcription factors such as Smads, NF-κB, STAT3, Snail, Twist, and Zeb that drive the epithelial-to-mesenchymal transition (EMT), in this study, we focus on the investigation in effects of SC-1 on TGFβ-induced interleukin-6 (IL-6) releases in an in vitro cell culture model. We showed that both intracellular IL-6 expression and secretion were stimulated by TGFβ and associated with strong upregulation of IL-6 mRNA and increased transcription in A549 cells. SC-1 blocked TGFβ-induced secretion of IL-6 while showing no effect on the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that SC-1 interferes with only a subset of TGFβ activities. In addition, SC-1 inhibits TGFβ-induced IL-6 by suppressing p38 MAPK signaling and subsequently inhibits NF-κB and its nuclear translocation without affecting the canonical Smad pathway and receptor turnover. Overall, these data suggest that p38 may involve in the inhibition of SC-1 in IL-6 release, thus illustrating an inhibitory effect for SC-1 in the suppression of inflammation, EMT phenotype, and tumorigenesis.
Background and Purpose
Haem oxygenase‐1 (HO‐1) is induced by thiazolidinediones including rosiglitazone and exerts anti‐inflammatory effects in various models. However, the molecular mechanisms ...underlying rosiglitazone‐induced HO‐1 expression remain largely unknown in human pulmonary alveolar epithelial cells (HPAEpiCs).
Experimental Approach
HO‐1 expression was determined by real time‐PCR, Western blotting and promoter reporter analyses. Signalling pathways were investigated using pharmacological inhibitors or specific siRNAs. Interactions between nuclear factor erythroid‐2‐related factor (Nrf2) and antioxidant response elements (ARE) binding site of the HO‐1 promoter were investigated with chromatin immunoprecipitation assays.
Key Results
Up‐regulation of HO‐1 in HPAEpiCs or in mice by rosiglitazone blunted ICAM‐1 expression and monocyte adhesion to HPAEpiCs challenged with LPS. Rosiglitazone‐induced HO‐1 expression was significantly attenuated by NADPH oxidase (NOX) inhibitors (apocynin and diphenyleneiodonium) or ROS scavenger (N‐acetyl cysteine). The involvement of NOX activity and ROS generation in rosiglitazone‐induced HO‐1 expression was confirmed by transfection with p47phox or NOX2 siRNA. Moreover, pretreatment with the inhibitors of c‐Src (c‐Srci II), proline‐rich tyrosine kinase 2 (Pyk2) (PF431396), Akt (Akti VIII) or PPARγ (GW9662) and transfection with siRNA of c‐Src, Pyk2, Akt or PPARγ abolished the rosiglitazone‐induced HO‐1 expression in HPAEpiCs. Subsequently, Nrf2 was activated by phosphorylation of c‐Src, Pyk2 and Akt, which turned on transcription of HO‐1 gene by binding to AREs binding site and enhancing ARE promoter activity.
Conclusions and Implications
Rosiglitazone induces HO‐1 expression via either NOX/ROS/c‐Src/Pyk2/Akt‐dependent Nrf2 activation or PPARγ in HPAEpiCs and suppresses LPS‐mediated inflammatory responses, suggesting that PPARγ agonists may be useful for protection against pulmonary inflammation.
Neuroinflammation is characterized by the elevated expression of various inflammatory proteins, including matrix metalloproteinases (MMPs), induced by various pro-inflammatory mediators, which play a ...critical role in neurodegenerative disorders. Interleukin-1β (IL-1β) has been shown to induce the upregulation of MMP-9 through nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-reactive oxygen species (ROS)-dependent signaling pathways. N-(2-cyano-3,12-dioxo-28-noroleana-1,9(11)-dien-17-yl)-2-2-difluoropropanamide (RTA 408), a novel synthetic triterpenoid, has been shown to possess anti-oxidant and anti-inflammatory properties in various types of cells. Here, we evaluated the effects of RTA 408 on IL-1β-induced inflammatory responses by suppressing MMP-9 expression in a rat brain astrocyte (RBA-1) line. IL-1β-induced MMP-9 protein and mRNA expression, and promoter activity were attenuated by RTA 408. The increased level of ROS generation in RBA-1 cells exposed to IL-1β was attenuated by RTA 408, as determined by using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and CellROX. In addition, the inhibitory effects of RTA 408 on MMP-9 expression resulted from the suppression of the IL-1β-stimulated activation of Pyk2 (proline-rich tyrosine kinase), platelet-derived growth factor receptor β (PDGFRβ), Akt, ROS, and mitogen-activated protein kinases (MAPKs). Pretreatment with RTA 408 attenuated the IL-1β-induced c-Jun phosphorylation, mRNA expression, and promoter activity. IL-1β-stimulated nuclear factor-κB (NF-κB) p65 phosphorylation, translocation, and promoter activity were also attenuated by RTA 408. Furthermore, IL-1β-induced glial fibrillary acidic protein (GFAP) protein and mRNA expression, and cell migration were attenuated by pretreatment with RTA 408. These results provide new insights into the mechanisms by which RTA 408 attenuates IL-1β-mediated inflammatory responses and exerts beneficial effects for the management of brain diseases.
Prediction of kidney function and chronic kidney disease (CKD) through kidney ultrasound imaging has long been considered desirable in clinical practice because of its safety, convenience, and ...affordability. However, this highly desirable approach is beyond the capability of human vision. We developed a deep learning approach for automatically determining the estimated glomerular filtration rate (eGFR) and CKD status. We exploited the transfer learning technique, integrating the powerful ResNet model pretrained on an ImageNet dataset in our neural network architecture, to predict kidney function based on 4,505 kidney ultrasound images labeled using eGFRs derived from serum creatinine concentrations. To further extract the information from ultrasound images, we leveraged kidney length annotations to remove the peripheral region of the kidneys and applied various data augmentation schemes to produce additional data with variations. Bootstrap aggregation was also applied to avoid overfitting and improve the model's generalization. Moreover, the kidney function features obtained by our deep neural network were used to identify the CKD status defined by an eGFR of <60 ml/min/1.73 m
. A Pearson correlation coefficient of 0.741 indicated the strong relationship between artificial intelligence (AI)- and creatinine-based GFR estimations. Overall CKD status classification accuracy of our model was 85.6% -higher than that of experienced nephrologists (60.3%-80.1%). Our model is the first fundamental step toward realizing the potential of transforming kidney ultrasound imaging into an effective, real-time, distant screening tool. AI-GFR estimation offers the possibility of noninvasive assessment of kidney function, a key goal of AI-powered functional automation in clinical practice.
Body posture and activity are important indices for assessing health and quality of life, especially for elderly people. Therefore, an easily wearable device or instrumented garment would be valuable ...for monitoring elderly people's postures and activities to facilitate healthy aging. In particular, such devices should be accepted by elderly people so that they are willing to wear it all the time. This paper presents the design and development of a novel, textile-based, intelligent wearable vest for real-time posture monitoring and emergency warnings. The vest provides a highly portable and low-cost solution that can be used both indoors and outdoors in order to provide long-term care at home, including health promotion, healthy aging assessments, and health abnormality alerts. The usability of the system was verified using a technology acceptance model-based study of 50 elderly people. The results indicated that although elderly people are anxious about some newly developed wearable technologies, they look forward to wearing this instrumented posture-monitoring vest in the future.
To advance the capabilities of probing chemical composition aloft, we designed a lightweight remote-controlled whole air sampling component (WASC) and integrated it into a multicopter drone with ...agile maneuverability to perform aerial whole air sampling. A field mission hovering over an exhaust shaft of a roadway tunnel to collect air samples was performed to demonstrate the applicability of the multicopter-carried WASC apparatus. Ten aerial air samples surrounding the shaft vent were collected by the multicopter-carried WASC. Additional five samples were collected manually inside the shaft for comparison. These samples were then analyzed in the laboratory for the chemical composition of 109 volatile organic compounds (VOCs), CH4, CO, CO2, or CO2 isotopologues. Most of the VOCs in the upwind samples (the least affected by shaft exhaust) were low in concentrations (5.9 ppbv for total 109 VOCs), posting a strong contrast to those in the shaft exhaust (235.8 ppbv for total 109 VOCs). By comparing the aerial samples with the in-shaft samples for chemical compositions, the influence of the shaft exhaust on the surrounding natural air was estimated. Through the aerial measurements, three major advantages of the multicopter-carried WASC were demonstrated: 1. The highly maneuverable multicopter-carried WASC can be readily deployed for three-dimensional environmental studies at a local scale (0−1.5 km); 2. Aerial sampling with superior sample integrity and preservation conditions can now be performed with ease; and 3. Data with spatial resolution for a large array of gaseous species with high precision can be easily obtained.
•A sampling device was integrated with a multicopter drone to perform aerial sampling.•The whole air sampling can be performed at desired positions aloft with ease.•The leak- and contamination-free properties ensured the integrity of air samples.•Subsequent in-lab analysis of whole air samples provided a large variety of species.•Vertical profiles of gaseous species up to 1 km height can be easily obtained.
Requirements of compressed sensing techniques targeted at miniaturized hyperspectral satellite applications include lightweight onboard hardware, high-speed sensing, low sampling rate for compressing ...the massive volume of typical hyperspectral data, and noise robustness for reliable data transmission to the ground station. We achieve all these aims via deep learning, and neural networks resulted from which can be implemented on-chip, thereby allowing light hardware implementation. Our neural networks were trained from small-scaled data, but, even so, the resulting encoder achieves a very low sampling rate and very high speed. Unlike typical network training, the input-output pairs are not square but stripe-like images, partly because compressed acquisition does not allow performing compression after obtaining complete data cube and partly because stripe-like acquisition well matches the popular pushbroom hyperspectral sensing schemes. Even with such hard restriction caused by nontraditional training, the resulting decoder still reconstructs the image with high accuracy. To match the requirement of pushbroom sensing, a lightweight encoder is proposed to compress the stripe-like images immediately. Meanwhile, multiscale feature fusion block (MFB) and aggregation (MFA) modules are proposed to form our decoder for enhancing the feature representation of the compressed acquisitions. Furthermore, we achieve joint spatial/spectral super-resolution (SR) progressively, ensuring accurate hyperspectral reconstruction via a low-rank-driven decoder. The encoder and decoder are trained in an end-to-end manner, where noise robustness is forced during the training stage. Comprehensive experiments demonstrate the superiority of the proposed hyperspectral compressed sensing method, as well as its one-shot transfer learning (OTL)-based extension, both quantitatively and qualitatively.
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