Adult-onset Still's disease (AOSD) is a multi-systemic inflammatory disorder of unknown etiology. To date, no single diagnostic test is available for AOSD. Herein, we investigated the pathogenic role ...of microRNAs in AOSD. MicroRNA profiles in plasma from AOSD patients and healthy controls were analyzed by microarray analysis, followed by quantitative reverse transcription PCR validation. The biological functions of microRNAs were evaluated using in vitro cell-based assay. Among the differentially expressed microRNAs, microRNA-134 (miR-134) expression was positively correlated with AOSD activity scores and significantly decreased after effective treatment. An increased miR-134 level is significantly associated with the activation of Toll-like receptor 3 (TLR3). The reporter assay identified IL-18 binding protein (IL-18BP) as the target of miR-134. A negative correlation between miR-134 expression and IL-18BP mRNA levels were detected in peripheral blood cells following TLR3 ligand treatment. Lower plasma IL-18BP levels and higher IL-18 levels were also observed in active AOSD patients who had higher miR-134 expression than inactive patients. Upregulation of circulating miR-134 was associated with elevated IL-18 levels by targeting IL-18BP in AOSD patients and was positively correlated with disease activity, suggesting its involvement in AOSD pathogenesis. MiR-134 may be a novel activity indicator or potential prognostic biomarker in AOSD.
A traumatic brain injury (TBI) causes abnormal proliferation of neuroglial cells, and over-release of glutamate induces oxidative stress and inflammation and leads to neuronal death, memory deficits, ...and even death if the condition is severe. There is currently no effective treatment for TBI. Recent interests have focused on the benefits of supplements or natural products like Ganoderma. Studies have indicated that immunomodulatory protein from Ganoderma microsporum (GMI) inhibits oxidative stress in lung cancer cells A549 and induces cancer cell death by causing intracellular autophagy. However, no evidence has shown the application of GMI on TBI. Thus, this study addressed whether GMI could be used to prevent or treat TBI through its anti-inflammation and antioxidative effects. We used glutamate-induced excitotoxicity as in vitro model and penetrating brain injury as in vivo model of TBI. We found that GMI inhibits the generation of intracellular reactive oxygen species and reduces neuronal death in cortical neurons against glutamate excitotoxicity. In neurite injury assay, GMI promotes neurite regeneration, the length of the regenerated neurite was even longer than that of the control group. The animal data show that GMI alleviates TBI-induced spatial memory deficits, expedites the restoration of the injured areas, induces the secretion of brain-derived neurotrophic factors, increases the superoxide dismutase 1 (SOD-1) and lowers the astroglial proliferation. It is the first paper to apply GMI to brain-injured diseases and confirms that GMI reduces oxidative stress caused by TBI and improves neurocognitive function. Moreover, the effects show that prevention is better than treatment. Thus, this study provides a potential treatment in naturopathy against TBI.
•GMI protects neurons and promotes neurite regeneration in the in vitro model of TBI.•GMI improves cognitive function through anti-oxidative and anti-inflammatory effects in the in vivo model of TBI.•This study is the first paper applying GMI, a potential treatment, to TBI.
Kubernetes, which is the most popular orchestration platform for Docker containers, is used widely for developing microservices and automating Docker instance life cycle administration. Because of ...advancements in containerization technology, a single server can run multiple services and use hardware resources more efficiently. However, containerized environments also bring new challenges in terms of complete monitoring and security provision. Thus, hackers can exploit the security vulnerabilities of containers to gain remote control permissions and cause extensive damage to company assets. Therefore, in this study, we propose KubAnomaly, a system that provides security monitoring capabilities for anomaly detection on the Kubernetes orchestration platform. We develop a container monitoring module for Kubernetes and implement neural network approaches to create classification models that strengthen its ability to find abnormal behaviors such as web service attacks and common vulnerabilities and exposures attacks. We use three types of datasets to evaluate our system, including privately collected and publicly available datasets as well as real‐world experiment data. Furthermore, we demonstrate the effectiveness of KubAnomaly by comparing its accuracy with that of other machine learning algorithms. KubAnomaly is shown to achieve an overall accuracy of up to 96% for anomaly detection. It successfully identifies four real attacks carried out by hackers in September 2018. Moreover, its performance overhead is only 5% greater than that of current methods. In summary, KubAnomaly significantly improves container security by avoiding anomaly
attacks.
We demonstrate the use of solution-processed molybdenum trioxide (MoO3) nanoparticle-decorated molybdenum disulfide (MoS2) nanosheets (MoS2/MoO3) as hole injection layer (HIL) in organic lighting ...diodes (OLEDs). The device performance is shown to be significantly improved by the introduction of such MoS2/MoO3 HIL without any post-ultraviolet-ozone treatment, and is shown to better the performance of devices fabricated using conventional poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) and MoO3 nanoparticle HILs. The MoS2/MoO3 nanosheets form a compact film, as smooth as PEDOT:PSS films and smoother than MoO3 nanoparticle films, when simply spin-coated on indium tin oxide substrates. The improvement in device efficiency can be attributed to the smooth surface of the nanostructured MoS2/MoO3 HIL and the excellent conductivity characteristics of the two-dimensional (2D) layered material (MoS2), which facilitate carrier transport in the device and reduce the sheet resistance. Moreover, the long-term stability of OLED devices that use such MoS2/MoO3 layers is shown to be improved dramatically compared with hygroscopic and acidic PEDOT:PSS-based devices.
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The development of osteochondral tissue engineering is an important issue for the treatment of traumatic injury or aging associated joint disease. However, the different compositions ...and mechanical properties of cartilage and subchondral bone show the complexity of this tissue interface, making it challenging for the design and fabrication of osteochondral graft substitute. In this study, a bilayer scaffold is developed to promote the regeneration of osteochondral tissue within a single integrated construct. It has the capacity to serve as a gene delivery platform to promote transfection of human mesenchymal stem cells (hMSCs) and the functional osteochondral tissues formation. For the subchondral bone layer, the bone matrix with organic (type I collagen, Col) and inorganic (hydroxyapatite, Hap) composite scaffold has been developed through mineralization of hydroxyapatite nanocrystals oriented growth on collagen fibrils. We also prepare multi-shell nanoparticles in different layers with a calcium phosphate core and DNA/calcium phosphate shells conjugated with polyethyleneimine to act as non-viral vectors for delivery of plasmid DNA encoding BMP2 and TGF-β3, respectively. Microbial transglutaminase is used as a cross-linking agent to crosslink the bilayer scaffold. The ability of this scaffold to act as a gene-activated matrix is demonstrated with successful transfection efficiency. The results show that the sustained release of plasmids from gene-activated matrix can promote prolonged transgene expression and stimulate hMSCs differentiation into osteogenic and chondrogenic lineages by spatial and temporal control within the bilayer composite scaffold. This improved delivery method may enhance the functionalized composite graft to accelerate healing process for osteochondral tissue regeneration.
In this study, a gene-activated matrix (GAM) to promote the growth of both cartilage and subchondral bone within a single integrated construct is developed. It has the capacity to promote transfection of human mesenchymal stem cells (hMSCs) and the functional osteochondral tissues formation. The results show that the sustained release of plasmids including TGF-beta and BMP-2 from GAM could promote prolonged transgene expression and stimulate hMSCs differentiation into the osteogenic and chondrogenic lineages by spatial control manner. This improved delivery method should enhance the functionalized composite graft to accelerate healing process in vitro and in vivo for osteochondral tissue regeneration.
We investigated whether the upper limb muscle stiffness quantified by the acoustic radiation force impulse shear wave elastography (ARFI/SWE) is a potential biomarker for age-related muscle ...alteration and functional decline in patients with Duchenne muscular dystrophy (DMD). 37 patients with DMD and 30 typically developing controls (TDC) were grouped by age (3-8, 9-11, and 12-18 years). ARFI/SWE measured the biceps and deltoid muscle's shear wave velocities (SWVs). Performance of Upper Limb Module (PUL 1.2 module) assessed muscle function in DMD patients. Mann Whitney test compared muscle SWVs between DMD and TDC, stratified by three age groups. We used analysis of variance with Bonferroni correction to compare muscle SWVs between DMD and TDC and correlated muscle SWVs with PUL results in the DMD group. Results showed that the SWVs of biceps differentiated DMD patients from TDC across age groups. Younger DMD patients (3-8 years) exhibited higher SWVs (p = 0.013), but older DMD patients (12-18 years) showed lower SWVS (p = 0.028) than same-aged TDC. DMD patients had decreasing biceps SWVs with age (p < 0.001), with no such age effect in TDC. The SWVs of deltoid and biceps positively correlated with PUL scores (r = 0.527 ∼ 0.897, P < 0.05) and negatively correlated with PUL timed measures (r = -0.425 ∼ -0.542, P < 0.05) in DMD patients. Our findings suggest that ARFI/SWE quantifying the SWVs in upper limb muscle could be a potential biomarker to differentiate DMD from TDC across ages and that DMD patients showed age-related muscle alteration and limb functional decline.
In this paper, we describe the application of the enantiomeric compounds YLC-1–YLC-4, each featuring a bulky spirofluorene-9,9′-phenanthren-10′-one moiety, as both hole-transporting materials (HTMs) ...and interfacial layers in both n–i–p and p–i–n perovskite solar cells (PSCs). These HTMs contain an enantiomeric mixture and a variety of core units linked to triarylamine donors to extend the degree of π-conjugation. The n–i–p PSCs incorporating YLC-1(a) exhibited a power conversion efficiency (PCE) of 19.15% under AM 1.5G conditions (100 mW cm–2); this value was comparable with that obtained using spiro-OMeTAD as the HTM (18.25%). We obtained efficient and stable p–i–n PSCs having the dopant-free structure indium tin oxide (ITO)/NiO x /interfacial layer (YLC)/perovskite/PC61BM/BCP/Ag. The presence of the spiro-based compounds YLC-1 and YLC-2 efficiently passivated the interfacial and grain boundary defects of the perovskite and enhanced the sizes of its grains, more so than did YLC-3 and YLC-4. These spiro-based YLC derivatives packed densely and functioned as Lewis bases to coordinate Pb and Ni ions in the perovskite and NiO x layers, respectively. Together, the effects of smaller grain boundaries and defect passivation of the perovskite enhanced the optoelectronic properties of the PSCs. The photoinduced charge carrier extraction in the linearly increasing voltage (photo-CELIV) curves of NiO x /YLC-1(a) showed the faster carrier transport 3.3 × 10–3 cm2 V–1 s–1, which improved the carrier mobility, supporting the notion of defect passivation of the perovskite. The best-performing NiO x /YLC-1(a) device provided a short-circuit current density (J SC) of 22.88 mA cm–2, an open-circuit voltage (V OC) of 1.10 V, and a fill factor (FF) of 80.93%, corresponding to an overall PCE of 20.37%. In addition, the PCEs of the NiO x /YLC-1(a) and NiO x /YLC-4(b) PSC devices underwent decays of only 98.1 and 97.0% of their original values after 41 days under an Ar atmosphere. Thus, these YLC derivatives passivated the NiO x surface and optimized the film quality of perovskites, thereby leading to superior PCEs of their respective PSCs.
(dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain ...unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of
, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (
= 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways.
BCL-2-associated X (BAX) protein acts as a gatekeeper in regulating mitochondria-dependent apoptosis. Under cellular stress, BAX becomes activated and transforms into a lethal oligomer that causes ...mitochondrial outer membrane permeabilization (MOMP). Previous studies have identified several structural features of the membrane-associated BAX oligomer; they include the formation of the BH3-in-groove dimer, the collapse of the helical hairpin α5–α6, and the membrane insertion of α9 helix. However, it remains unclear as to the role of lipid environment in determining the conformation and the pore-forming activity of the BAX oligomers. Here we study molecular details of the membrane-associated BAX in various lipid environments using fluorescence and ESR techniques. We identify the inactive versus active forms of membrane-associated BAX, only the latter of which can induce stable and large membrane pores that are sufficient in size to pass apoptogenic factors. We reveal that the presence of CL is crucial to promoting the association between BAX dimers, hence the active oligomers. Without the presence of CL, BAX dimers assemble into an inactive oligomer that lacks the ability to form stable pores in the membrane. This study suggests an important role of CL in determining the formation of active BAX oligomers.
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•Membrane-associated BAX can exist in either inactive or active form.•Cardiolipin is crucial to promoting the activated BAX oligomers.•Cardiolipin is important to promote BAX to induce large membrane pores.•In a PC-only environment, BAX associates with lipids to form an inactive oligomer.
Introduction
18F‐fluorodeoxyglucose (FDG)‐PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the ...topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti‐NMDAR and anti‐AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis.
Methods
The cerebral glucose metabolism was evaluated by FDG‐PET/CT during acute‐to‐subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z‐score and visualized on three‐dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities.
Results
The three‐dimensional stereotactic surface projection displayed frontal‐dominant hypometabolism in a 66‐year‐old female patient with anti‐AMPAR encephalitis and occipital‐dominant hypometabolism in a 29‐year‐old female patient with anti‐NMDAR encephalitis. Receptor density maps revealed opposite frontal–occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG‐PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypermetabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti‐NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery.
Conclusions
The distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG‐PET of brain a valuable diagnostic tool.
Glucose metabolism patterns were different in anti‐AMPAR and anti‐NMDAR encephalitis. Hypometabolism was frontal‐dominant in anti‐AMPAR encephalitis but occipital‐dominant in anti‐NMDAR encephalitis. The topographical differences might be related to receptor density.
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