Osteoarthritis (OA), the most prevalent age-related joint disorder, is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. Accumulating ...evidences indicate that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. Here we showed that circRNA.33186 was significantly upregulated in IL-1β)-treated chondrocytes and in cartilage tissues of a destabilized medial meniscus (DMM)-induced OA mouse model. Knockdown of circRNA.33186 increased anabolic factor (type II collagen) expression and decreased catabolic factor (MMP-13) expression. Knockdown of circRNA.33186 also promoted proliferation and inhibited apoptosis in IL-1β-treated chondrocytes. Silencing of circRNA.33186 in vivo markedly alleviated DMM-induced OA. Mechanistic study showed that circRNA.33186 directly binds to and inhibits miR-127-5p, thereby increasing MMP-13 expression, and contributes to OA pathogenesis. Taken together, our findings demonstrated a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy.
Zhu and colleagues demonstrate that circRNA.33186 regulates chondrocyte functions, including ECM catabolism, proliferation, and apoptosis. Silencing of circRNA.33186 alleviated OA by acting as a sponge of miR-127-5p. These findings reveal a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy.
Cytosolic double‐stranded DNA (dsDNA) is a danger signal that is tightly monitored and sensed by nucleic acid‐sensing pattern recognition receptors. We study the inflammatory cascade on dsDNA ...recognition and investigate the neuroprotective effect of cyclic GMP‐AMP (cGAMP) synthase (cGAS) antagonist A151 and its mechanisms of neuroprotection in a mouse model of experimental stroke. Here, we found that cerebral ischemia promoted the release of dsDNA into the cytosol, where it initiated inflammatory responses by activating the cGAS. A151 effectively reduced the expression of cGAS, absent in melanoma 2 (AIM2) inflammasome, and pyroptosis‐related molecules, including caspase‐1, gasdermin D, IL‐1β, and IL‐18. Furthermore, mice treated with A151 showed a dampened immune response to stroke, with reduced counts of neutrophils, microglia, and microglial production of IL‐6 and TNF‐α after MCAO. Moreover, A151 administration significantly reduced infarct volume, attenuated neurodeficits, and diminished cell death. Notably, the protective effect of A151 was blocked in a microglia‐specific cGAS knockout mouse. These findings offer unique perspectives on stroke pathogenesis and indicate that inhibition of cGAS could attenuate brain inflammatory burden, representing a potential therapeutic opportunity for stroke.
Synopsis
Inflammation is involved in the progression of ischemic brain injury. This study focuses on the inflammatory cascade on double‐strand DNA (dsDNA) recognition and highlights the possibility of inhibiting dsDNA‐sensing cyclic GMP‐AMP synthase (cGAS) for treatment of ischemic stroke.
The release of dsDNA from necrotic tissue during brain infarction triggers an innate inflammatory cascade.
A synthetic oligonucleotide A151 that antagonizes cGAS regulates the microglial immune response and pyroptosis after ischemic stroke.
Inhibition of cGAS leads to a decline in neutrophil infiltration into the brain.
Suppression of the dsDNA‐sensing cGAS pathway reduces ischemic brain injury via mitigating neuroinflammation.
Inflammation is involved in the progression of ischemic brain injury. This study focuses on the inflammatory cascade on double‐strand DNA (dsDNA) recognition and highlights the possibility of inhibiting dsDNA‐sensing cyclic GMP‐AMP synthase (cGAS) for treatment of ischemic stroke.
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•Effects of substrate concentration on anammox start-up were studied.•Lower NLR of R1 accelerated the formation of anammox sludge.•R2 with higher NLR obtained greater anammox ...activity.•R2 obtained higher tolerance against high impact of nitrogen load.
Two up-flow blanket filter (UBF) reactors were employed to treat synthetic wastewater with different substrate concentrations and nitrogen load rates (NLR) for 178days. During days 0–60, higher influent NLR of R2 (0.21–0.58kg·m3·d) slowed down the formation of anammox sludge compared with the lower NLR of R1 (0.18–0.31kg·m3·d). Difference in sludge color and nitrogen conversion rate indicated greater anammox activity of R2 than R1. During days 61–178, R1 and R2 achieved the maximum nitrogen removal rates (NRR) of 1.213 and 1.684kg/(m3·d) under the NLRs of 1.924 and 2.502kg/(m3·d), respectively. Furthermore, high-throughput sequencing showed that R2 (43.5%) had a higher proportion of anammox bacteria than R1 (37.8%) and less species. These results showed that after going through a higher NLR acclimation process during start-up period, stronger resistant capability against high impact nitrogen load and greater anammox activity were obtained by R2.
Long non-coding RNAs (lncRNAs) have emerged as novel gene regulators in multiple tumorigenesis and chemoresistance. However, their potential roles and molecular mechanisms in gastric cancer ...chemoresistance remain unclear. In present study, our team investigated the role and potential regulatory mechanism of lncRNA s bladder cancer associated transcript-1 (BLACAT1) in the gastric cancer chemoresistance. Results showed that BLACAT1 expression was up-regulated in the oxaliplatin (OXA) resistant gastric cancer tissue and cells compared with OXA-sensitive tissue and parental cell lines. In vitro, BLACAT1 knockdown decreased the expression levels of drug resistance related genes and ABCB1 protein. Besides, BLACAT1 knockdown significantly promoted apoptosis and down-regulated the invasion and the IC50 value of oxaliplatin. In vivo, BLACAT1 knockdown suppressed the tumor growth of gastric cancer cells. Bioinformatics tools and luciferase assay indicated that miR-361 both targeted 3′-UTR of BLACAT1 and ABCB1mRNA, suggesting the BLACAT1/miR-361/ABCB1 regulatory pathway. In summary, our results conclude that BLACAT1 accelerates the oxaliplatin-resistance of gastric cancer via promoting ABCB1 protein expression by targeting miR-361, providing a novel insight for the chemoresistance of gastric cancer.
Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the ...nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the components of NLRP3 inflammasome NLRP3, Casp-1 p20/Casp-1 p45 ratio, proIL-1β and IL-1β and also enhanced autophagy (LC3-II/LC3-I ratio, Beclin-1 and SQSTM1). Pretreatment of peritoneal macrophages with HU 308, a selective CB2R agonist, attenuated LPS/DSS-induced NLRP3 inflammasome activation, but further enhanced autophagy. In comparison with wild-type (WT) control, peritoneal macrophages from CB2R knockout (KO) mice had more robust NLRP3 inflammasome activation and attenuated autophagy upon LPS/DSS challenge. Knockdown autophagy-related gene 5 (Atg5) with a siRNA in peritoneal macrophages attenuated the inhibitory effects of HU 308 on LPS/DSS-induced NLRP3 inflammasome activation in vitro. In vivo, HU308 treatment attenuated DSS-induced colitis mice associated with reduced colon inflammation and inhibited NLRP3 inflammasome activation in wild-type mice. In CB2R KO mice, DSS-induced inflammation and NLRP3 inflammasome activation were more pronounced than those in WT control. Finally, we demonstrated that AMPK-mTOR-P70S6K signaling pathway was involved in this CB2R-mediated process. We conclude that activation of CB2R ameliorates DSS-induced colitis through enhancing autophagy that may inhibit NLRP3 inflammasome activation in macrophages.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A series of novel Fe-Cd co-doped ZnO nanoparticle based photocatalysts are successfully synthesized by sol-gel route and characterized using scanning electron microscopy (SEM), energy dispersive ...X-ray emission (EDX), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-Vis spectroscopy, X-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) techniques. The photocatalytic activity of ZnO nanoparticles doped with various atomic weight fraction of Fe and Cd has been investigated under visible light irradiation using the Methylene Blue and Rhodamine B dye in aqueous solution. The FeCd (2%):ZnO (ZFC-1) exhibit the highest photocatalytic activity in terms of rate constant as K
= 0.01153 min
and K
= 0.00916 min
). Further, the re-usability of the ZFC-1 photocatalyst is studied which confirms that it can be reused up to five times with nearly negligible loss of the photocatalytic efficiency. Moreover, the role of photoactive species investigated using a radical scavenger technique. The present investigations show that the doping concentration plays significant role in photocatalytic performance. The visible light absorption shown by Fe-Cd co-doped ZnO nanoparticles is much higher than that of undoped body probably due to co-doping, and the charge carrier recombination is decreased effectively which yields a higher photocatalytic performance. The mechanism for the enhancement of photocatalytic activity under visible light irradiation is also proposed.
Compared to time-consuming and unreliable manual analysis, intelligent fault diagnosis techniques using deep learning models can improve the accuracy of intelligent fault diagnosis with their ...multi-layer nonlinear mapping capabilities. This paper proposes a model to perform fault diagnosis and classification by using a time series of vibration sensor data as the input. The model encodes the raw vibration signal into a two-dimensional image and performs feature extraction and classification by a deep convolutional neural network or improved capsule network. A fault diagnosis technique based on the Gramian Angular Field (GAF), the Markov Transition Field (MTF), and the Capsule Network is proposed. Experiments conducted on a bearing failure dataset from Case Western Reserve University investigated the impact of two coding methods and different network structures on the diagnosis accuracy. The results show that the GAF technique retains more complete fault characteristics, while the MTF technique contains a small number of fault characteristics but more dynamic characteristics. Therefore, the proposed method incorporates GAF images and MTF images as a dual-channel image input to the capsule network, enabling the network to obtain a more complete fault signature. Multiple sets of experiments were conducted on the bearing fault dataset at Case Western Reserve University, and the Capsule Network in the proposed model has an advantage over other convolutional neural networks and performs well in the comparison of fault diagnosis methods proposed by other researchers.
Photocatalytic conversion of diluted CO2 into solar fuel is highly appealing yet still in its infancy. Herein, we demonstrate the metal‐node‐dependent performance for photoreduction of diluted CO2 by ...constructing Ni metal–organic framework (MOF) monolayers (Ni MOLs). In diluted CO2 (10 %), Ni MOLs exhibit a highest apparent quantum yield of 1.96 % with a CO selectivity of 96.8 %, which not only exceeds reported systems in diluted CO2 but also is superior to most catalysts in pure CO2. Whereas isostructural Co MOLs is almost inactive in diluted CO2, indicating the performance is dependent on the metal nodes. Experimental and theoretical investigations show that strong CO2 binding affinity of Ni MOLs is the crucial factor, which stabilizes the Ni‐CO2 adducts and facilitates CO2‐to‐CO conversion.
Doctor node: Photocatalytic conversion of diluted CO2 with high efficiency and selectivity can be achieved on Ni metal–organic framework (MOF) monolayers (Ni MOLs). The initial adsorption of CO2 molecules is the critical step and depends on the nature of the metal node.
The fifth generation (5G) of mobile communication system aims to deliver a ubiquitous mobile service with enhanced quality of service (QoS). It is also expected to enable new use-cases for various ...vertical industrial applications-such as automobiles, public transportation, medical care, energy, public safety, agriculture, entertainment, manufacturing, and so on. Rapid increases are predicted to occur in user density, traffic volume, and data rate. This calls for novel solutions to the requirements of both mobile users and vertical industries in the next decade. Among various available options, one that appears attractive is to redesign the network architecture-more specifically, to reconstruct the radio access network (RAN). In this paper, we present an inclusive and comprehensive survey on various RAN architectures toward 5G, namely cloud-RAN, heterogeneous cloud-RAN, virtualized cloud-RAN, and fog-RAN. We compare them from various perspectives, such as energy consumption, operations expenditure, resource allocation, spectrum efficiency, system architecture, and network performance. Moreover, we review the key enabling technologies for 5G systems, such as multi-access edge computing, network function virtualization, software-defined networking, and network slicing; and some crucial radio access technologies (RATs), such as millimeter wave, massive multi-input multi-output, device-to-device communication, and massive machine-type communication. Last but not least, we discuss the major research challenges in 5G RAN and 5G RATs and identify several possible directions of future research.
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