Protective effect of furofuranone against cerebral ischemic stroke via activation of PI3k/Akt/GSK 3β signaling pathway

Purpose: To study the protective effects of furofuranone on oxygen and glucose-deprived damage to brain microvascular endothelial cells (BMECs) in vitro, and in vivo in cerebral ischemic stroke rat model. Methods: BMECs were isolated from the Sprague Dawley rats and deprived of oxygen and glucose. The effect of 10, 20, 30, 40, 50 and 100 µM furofuranone on the oxygen/glucose-deprived BMECs was studied using Transwell chamber method. A rat cerebral ischemic stroke model was established using middle cerebral arterial occlusion method. Caspase-3 and other proteins, inflammatory cytokines, and other parameters of the brain tissue were evaluated by enzyme-linked assay (ELISA), polymerase chain reaction (PCR) and Western blot as appropriate. Further studies on the brain tissues was carried out by immunochemical analysis and hematoxylin and eosin staining. Results: Furofuranone decreased caspase 3 levels in a dose-based manner in rat BMECs, and significantly reduced the release of lactate dehydrogenase (LDH) in ischemic stroke rat model (p < 0.05). It also led to marked increases in the levels of p PI3k, p Akt and p GSK3β in cerebral ischemic stroke rats. Growth-associated protein-43 (GAP-43) and microtubule-associated protein 2 (MAP-2) levels increased in the cerebral ischemic stroke rat brain tissues, in addition to marked increase in ionized calcium-binding adaptor protein (IBA-1) and glial fibrillary acidic protein (GFAP) (p < 0.05). Furofuranone treatment reduced the population of microtubule-associated protein light chain 3 (MAP1LC3A) and Beclin 1-positive cells, and significantly downregulated L selectin, leptin, monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor (TNF)-α (p < 0.05). The release of tissue inhibitor of metalloproteinases 1 (TIMP-1) was enhanced in the cerebral ischemic stroke rats by furofuranone treatment. Conclusion: Furofuranone treatment prevents cerebral ischemic stroke-induced damage in rats via phosphorylation of PI3k, Akt and GSK3β proteins, and reduction of inflammatory cytokine levels. Therefore, furofuranone may be useful as chemotherapeutic agent for cerebral ischemic stroke

NeuralMarker: A Framework for Learning General Marker Correspondence

We tackle the problem of estimating correspondences from a general marker, such as a movie poster, to an image that captures such a marker. Conventionally, this problem is addressed by fitting a homography model based on sparse feature matching. However, they are only able to handle plane-like markers and the sparse features do not sufficiently utilize appearance information. In this paper, we propose a novel framework NeuralMarker, training a neural network estimating dense marker correspondences under various challenging conditions, such as marker deformation, harsh lighting, etc. Besides, we also propose a novel marker correspondence evaluation method circumstancing annotations on real marker-image pairs and create a new benchmark. We show that NeuralMarker significantly outperforms previous methods and enables new interesting applications, including Augmented Reality (AR) and video editing.Comment: Accepted by ToG (SIGGRAPH Asia 2022). Project Page: https://drinkingcoder.github.io/publication/neuralmarker

RD-VIO: Robust Visual-Inertial Odometry for Mobile Augmented Reality in Dynamic Environments

It is typically challenging for visual or visual-inertial odometry systems to handle the problems of dynamic scenes and pure rotation. In this work, we design a novel visual-inertial odometry (VIO) system called RD-VIO to handle both of these two problems. Firstly, we propose an IMU-PARSAC algorithm which can robustly detect and match keypoints in a two-stage process. In the first state, landmarks are matched with new keypoints using visual and IMU measurements. We collect statistical information from the matching and then guide the intra-keypoint matching in the second stage. Secondly, to handle the problem of pure rotation, we detect the motion type and adapt the deferred-triangulation technique during the data-association process. We make the pure-rotational frames into the special subframes. When solving the visual-inertial bundle adjustment, they provide additional constraints to the pure-rotational motion. We evaluate the proposed VIO system on public datasets. Experiments show the proposed RD-VIO has obvious advantages over other methods in dynamic environments

Electrically controlling vortices in a neutral exciton polariton condensate at room temperature

Manipulating bosonic condensates with electric fields is very challenging as the electric fields do not directly interact with the neutral particles of the condensate. Here we demonstrate a simple electric method to tune the vorticity of exciton polariton condensates in a strong coupling liquid crystal (LC) microcavity with CsPbBr$_3$ microplates as active material at room temperature. In such a microcavity, the LC molecular director can be electrically modulated giving control over the polariton condensation in different modes. For isotropic non-resonant optical pumping we demonstrate the spontaneous formation of vortices with topological charges of +1, +2, -2, and -1. The topological vortex charge is controlled by a voltage in the range of 1 to 10 V applied to the microcavity sample. This control is achieved by the interplay of a built-in potential gradient, the anisotropy of the optically active perovskite microplates, and the electrically controllable LC molecular director in our system with intentionally broken rotational symmetry. Besides the fundamental interest in the achieved electric polariton vortex control at room temperature, our work paves the way to micron-sized emitters with electric control over the emitted light's phase profile and quantized orbital angular momentum for information processing and integration into photonic circuits

Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review

BackgroundNeuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID.Materials and methodsWe presented two cases of NIID diagnosed by using NOTCH2NLC gene testing and skin biopsy. Diffusion weighted imaging (DWI) showed high linear intensity in corticomedullary junction. We also reviewed all the published NIID cases with positive NOTCH2NLC GGC repeat expansion and skin biopsy results in PubMed.ResultsPatient 1 was a 63-year-old male who carried 148 GGC repeats and presented with progressive tremor and limb weakness. Patient 2 was a 62-year-old woman who carried 131 GGC repeats and presented with tremors, memory loss and headaches. The most common clinical manifestation of 63 NIID patients in this study was cognitive impairment, followed by tremors. In our study, almost all the patients were from East Asia, the male to female ratio was 1:1.26, with an age of onset of 54.12 ± 14.12 years, and an age of diagnosis of 60.03 ± 12.21 years. Symmetrical high signal intensity at the corticomedullary junction on DWI were revealed in 80.96% of the patients. For the GGC repeat numbers, the majority of GGC repeats were in the 80–119 intervals, with few GGC repeats above 160. The number of GGC repetitions was significantly higher in patients presented with muscle weakness than in other clinical manifestations.ConclusionNIID is a neurodegenerative disease caused by aberrant polyglycine (polyG) protein aggregation. NIID mostly occurs in the elderly population in East Asia, with cognitive dysfunction as the most common symptom. Staging NIID based on clinical presentation is inappropriate because most patients with NIID have overlapping symptoms. In our study, there was no significant correlation between the number of GGC repeats and different phenotypes except for muscle weakness. Abnormal trinucleotides repeat and PolyG protein aggregation maybe common pathogenic mechanism in neurodegenerative diseases and cerebrovascular diseases, which needs to be confirmed by more studies

More Severe Manifestations and Poorer Short-Term Prognosis of Ganglioside-Associated Guillain-Barré Syndrome in Northeast China

Ganglioside as a neurotrophic drug has been hitherto widely used in China, although Guillain-Barré syndrome (GBS) following intravenous ganglioside treatment was reported in Europe several decades ago. We identified 7 patients who developed GBS after intravenous use of gangliosides (ganglioside+ group) and compared their clinical data with those of 77 non-ganglioside-associated GBS patients (ganglioside− group) in 2013, aiming at gaining the distinct features of ganglioside-associated GBS. Although the mean age, protein levels in cerebrospinal fluid (CSF) and frequency of cranial nerve involvement were similar between the two groups, the Hughes Functional Grading Scale (HFGS) score and the Medical Research Council (MRC) sum score at nadir significantly differed (4.9±0.4 vs 3.6±1.0; 7.7±5.5 vs 36.9±14.5, both p<0.001), indicating a higher disease severity of ganglioside-associated GBS. A higher ratio of patients with ganglioside-associated GBS required mechanical ventilation (85.7% vs 15.6%, p<0.01). The short-term prognosis of ganglioside-associated GBS, as measured by the HFGS score and the MRC sum score at discharge, was poorer (4.3±0.5 vs 2.8±1.1; 17.3±12.9 vs 46.0±13.9, both p<0.001). All the patients in the ganglioside+ group presented an axonal form of GBS, namely acute motor axonal neuropathy (AMAN). When compared with the AMAN patients in the ganglioside− group, more severe functional deficits at nadir and poorer recovery after standard treatment were still prominent in ganglioside-associated GBS. Anti-GM1 and anti-GT1a antibodies were detectable in patients with AMAN while not in patients with the demyelinating subtype of GBS. The concentrations of these antibodies in patients with AMAN were insignificantly different between the ganglioside+ and ganglioside− groups. In sum, ganglioside-associated GBS may be a devastating side effect of intravenous use of gangliosides, which usually manifests a more severe clinical course and poorer outcome

Single-shot spatial instability and electric control of polariton condensates at room temperature

In planar microcavities, the transverse-electric and transverse-magnetic (TE-TM) mode splitting of cavity photons arises due to their different penetration into the Bragg mirrors and can result in optical spin-orbit coupling (SOC). In this work, we find that in a liquid crystal (LC) microcavity filled with perovskite microplates, the pronounced TE-TM splitting gives rise to a strong SOC that leads to the spatial instability of microcavity polariton condensates under single-shot excitation. Spatially varying hole burning and mode competition occurs between polarization components leading to different condensate profiles from shot to shot. The single-shot polariton condensates become stable when the SOC vanishes as the TE and TM modes are spectrally well separated from each other, which can be achieved by application of an electric field to our LC microcavity with electrically tunable anisotropy. Our findings are well reproduced and traced back to their physical origin by our detailed numerical simulations. With the electrical manipulation our work reveals how the shot-to-shot spatial instability of spatial polariton profiles can be engineered in anisotropic microcavities at room temperature, which will benefit the development of stable polariton-based optoeletronic and light-emitting devices

Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer

Background: Lysine specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics, but the pathological roles of its dysfunction in lung cancer remain to be elucidated. The aim of this study was to evaluate the prognostic significance of LSD1 expression in patients with non-small cell lung cancer (NSCLC) and to define its exact role in lung cancer proliferation, migration and invasion. Methods: The protein levels of LSD1 in surgically resected samples from NSCLC patients were detected by immunohistochemistry or Western blotting. The mRNA levels of LSD1 were detected by qRT-PCR. The correlation of LSD1 expression with clinical characteristics and prognosis was determined by statistical analysis. Cell proliferation rate was assessed by MTS assay and immunofluorescence. Cell migration and invasion were detected by scratch test, matrigel assay and transwell invasion assay. Results: LSD1 expression was higher in lung cancer tissue more than in normal lung tissue. Our results showed that overexpression of LSD1 protein were associated with shorter overall survival of NSCLC patients. LSD1 was localized mainly to the cancer cell nucleus. Interruption of LSD1 using siRNA or a chemical inhibitor, pargyline, suppressed proliferation, migration and invasion of A549, H460 and 293T cells. Meanwhile, over-expression of LSD1 enhanced cell growth. Finally, LSD1 was shown to regulate epithelial-to-mesenchymal transition in lung cancer cells

A Novel Compound C12 Inhibits Inflammatory Cytokine Production and Protects from Inflammatory Injury In Vivo

Inflammation is a hallmark of many diseases. Although steroids and cyclooxygenase inhibitors are main anti-inflammatory therapeutical agents, they may cause serious side effects. Therefore, developing non-steroid anti-inflammatory agents is urgently needed. A novel hydrosoluble compound, C12 (2,6-bis(4-(3-(dimethylamino)-propoxy)benzylidene)cyclohexanone), has been designed and synthesized as an anti-inflammatory agent in our previous study. In the present study, we investigated whether C12 can affect inflammatory processes in vitro and in vivo. In mouse primary peritoneal macrophages, C12 potently inhibited the production of the proinflammatory gene expression including TNF-α, IL-1β, IL-6, iNOS, COX-2 and PGE synthase. The activity of C12 was partly dependent on inhibition of ERK/JNK (but p38) phosphorylation and NF-κB activation. In vivo, C12 suppressed proinflammatory cytokine production in plasma and liver, attenuated lung histopathology, and significantly reduced mortality in endotoxemic mice. In addition, the pre-treatment with C12 reduced the inflammatory pain in the acetic acid and formalin models and reduced the carrageenan-induced paw oedema and acetic acid-increased vascular permeability. Taken together, C12 has multiple anti-inflammatory effects. These findings, coupled with the low toxicity and hydrosolubility of C12, suggests that this agent may be useful in the treatment of inflammatory diseases