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Objectives After ischemic stroke, microglia will be activated and play a key role in neuroinflammation and the destruction of the blood-brain barrier (BBB), and activated microglia could polarize into pro-inflammation M1 phenotype and anti-inflammation M2 phenotype. Dimethyl malonate (DMM) could reduce reactive oxygen species and we speculate DMM could regulate microglia to protect ischemic brain. Methods We used transient middle cerebral artery occlusion (tMCAO) mouse model to simulate ischemic stroke and adult male C57BL/6 mice were used in our study. 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct volume. Evans Blue and Brain water content were used to evaluate the destruction of BBB. We used a five-point scale to assess the neurologic function of mice. Western blot and Immunofluorescence were used to measure microglia, pericytes and the expression of related proteins. Results DMM reduced cerebral infarct volume, Evans blue leakage, brain water content and improved neurologic deficits after tMCAO. The number of activated microglia and M1 microglia were decreased and the number of M2 microglia and pericytes were increased after DMM treatment. The expression of tumor necrosis factor-α was reduced while protein levels of IL-10 and ZO-1 were increased through DMM treatment. Conclusions DMM could regulate activation and polarization of microglia to inhibit neuroinflammation and protect BBB.

In this retrospective study we assessed the efficacy and safety of tocilizumab in patients with critical or severe coronavirus disease 2019 (COVID-19). We enrolled 181 patients admitted to Huoshenshan Hospital (Wuhan, China) with confirmed COVID-19 between January 2020 and February 2020. Ninety-two patients were treated with tocilizumab, and 89 patients were treated conventionally. We analyzed the clinical manifestations, changes in CT scan images, and laboratory tests before and after tocilizumab treatment, and compared these results with the conventionally treated group. A significant reduction in the level of C-reactive protein was observed 1 week after tocilizumab administration. In some cases this meant the end of the IL-6-related cytokine storm. In addition, tocilizumab relieved fever, cough, and shortness of breath with no reported adverse drug reactions. These findings suggest tocilizumab improves clinical outcomes and is effective for treatment of patients with critical or severe COVID-19. However, future clinical trials are needed to better understand the impact of tocilizumab interference with IL-6 and provide a therapeutic strategy for treatment of COVID-19.

Male reproductive health has become a concern in public health, and semen quality is essential to male reproduction. To investigate the geographical differences in semen quality of sperm donors from the north and south of China, a total of 1012 sperm donors from all over China were enrolled in this work, which were divided by their residential latitude. There were statistically significant differences in sperm concentration among men from different latitudes in China(P=0.04). The sperm concentrations of people from 18°-27° north latitude were lower than those from 36°-45°, and 45°-54° (median 131, 134, 146, respectively, P=0.021[18°-27° vs. 36°-45°] and P=0.01[18°-27° vs. 45°-54°]). It was further confirmed when the samples were re-divided into 2 groups (typically north and south) that contains 667 samples. The analysis also showed a significant difference in terms of the regions to which the samples belonged (the median of the north is 134; the median of the south is 125; P =0.015). Although other sperm parameters don’t show significant change with latitude, some of them possess a strong relationship with sperm concentration (r=-0.19364, P

Objective. Spontaneous intracerebral hemorrhage (ICH) is a blood clot arising in the brain parenchyma in the absence of trauma or surgery and accounts for 10% to 15% of all strokes, leading to higher rates of mortality and morbidity than either ischemic stroke or subarachnoid hemorrhage. We sought to investigate the potential association of DOCK1 with neurological deficits and outcomes in patients with spontaneous ICH. Methods. Identification of methylation-regulated differentially expressed genes (MeDEGs) between ICH patients and matched controls was performed by analyzing the raw data from the GSE179759 and GSE125512 datasets deposited in the Gene Expression Omnibus. A total of 114 patients who were admitted to our hospital for spontaneous ICH were retrospectively analyzed, with 108 healthy volunteers who had received physical examinations at the same period as controls. The mRNA expression of DOCK1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The hematoma volume was calculated according to the Coniglobus formula. The severity of neurological deficits was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores and function outcomes were evaluated by modified Rankin Scale (mRS) scores. Results. A total of 15 MeDEGs between ICH patients and matched controls were identified. The mRNA expression of DOCK1 was remarkably higher in the serum samples of patients with spontaneous ICH than in the healthy controls. According to hematoma volume after ICH attack, small (30 mL) groups were arranged. The proportions of male patients and patients aged ≥60 years were significantly higher in the large group than in the small and medium groups ( P < 0.05 ). The mRNA expression of DOCK1 was significantly higher in the large group than in the small and medium groups ( P < 0.05 ). According to NIHSS scores, mild (NIHSS scores ≤15), moderate (NIHSS scores from 16 to 30), and severe (NIHSS scores from 31 to 45) groups were classified. It was observed that the severe group had higher proportions of male patients and patients aged ≥60 years than the mild and moderate groups ( P < 0.05 ). The severe group exhibited a higher mRNA expression of DOCK1 than the mild and moderate groups ( P < 0.05 ). According to mRS scores, higher proportions of male patients and patients aged ≥60 years were observed in the unfavorable group than the favorable group ( P < 0.05 ). The patients in the unfavorable group showed an elevated DOCK1 mRNA expression compared to those in the favorable group ( P < 0.05 ). Conclusion. The study provided evidence that male gender, older age, and higher DOCK1 mRNA expression were related to higher admission hematoma volume, neurologic deterioration, and poor function outcomes in patients with spontaneous ICH.

Triple-negative breast cancer (TNBC), defined by the lack of expression of estrogen, progesterone, and ERBB2 receptors, has the worst prognosis of all breast cancers. It is difficult to treat owing to a lack of effective molecular targets. Here, we report that the growth of TNBC cells is exceptionally dependent on PICH, a DNA-dependent ATPase. Clinical samples analysis showed that PICH is highly expressed in TNBC compared to other breast cancer subtypes. Importantly, its high expression correlates with higher risk of distal metastasis and worse clinical outcomes. Further analysis revealed that PICH depletion selectively impairs the proliferation of TNBC cells, but not that of luminal breast cancer cells, in vitro and in vivo. In addition, knockdown of PICH in TNBC cells induces the formation of chromatin bridges and lagging chromosomes in anaphase, frequently resulting in micronucleation or binucleation, finally leading to mitotic catastrophe and apoptosis. Collectively, our findings show the dependency of TNBC cells on PICH for faithful chromosome segregation and the clinical potential of PICH inhibition to improve treatment of patients with high-risk TNBC.

Teriflunomide has been reported to inhibit microglial activation in experimental models of traumatic brain injury. However, its roles in ischemic stroke and underlying mechanisms of action are still undiscovered. In this study, we investigated the effects of teriflunomide on brain edema, neurologic deficits, infarct volume, neuroinflammation, blood-brain barrier (BBB) permeability, and neurogenesis in a mouse model of transient middle cerebral artery occlusion (tMCAO). tMCAO mice treated with teriflunomide showed lower brain water content on day 3, milder neurologic deficits and smaller infarct volume on day 7 than those treated with vehicle. Additionally, mice received teriflunomide had fewer activated Iba-1-positive microglia and lower protein levels of interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and 3-Nitrotyrosine (3-NT) compared with those received vehicle on day 3. Further, teriflunomide alleviated Evans blue dye leakage, increased pericyte coverage and protein levels of platelet-derived growth factor B (PDGFB), platelet-derived growth factor receptor β (PDGFRβ) and Bcl2, and decreased the number of PDGFRβ/matrix metalloproteinase 9 (MMP9)-positive cells. Moreover, teriflunomide reduced the loss of zonula occludens-1 (ZO-1) and occludin. Finally, teriflunomide significantly upregulated the number of 5-bromo-20-deoxyuridine (BrdU)/doublecortin (DCX)-positive cells and expression of mammalian achaete-scute homolog 1 (Mash1), DCX and Pbx1 in subventricular zone (SVZ) on day 7 after stroke. Our results indicate that teriflunomide exhibits protective roles in ischemic stroke by inhibiting neuroinflammation, alleviating BBB disruption and enhancing neurogenesis.

Some test systems for voice cloud services have been developed in recent years. However, the automobile manufacturers, communications equipment merchants and network operator still lacks methods and tools to evaluate the vehicular voice cloud services from the perspective of the end user experience. Considering the user behavior and user experience, a light weight vehicular voice cloud evaluation system is designed in this paper. The system is able to send voice information to voice cloud server according to user habit, and record the user experience indicators, such as accurate, voice quality, service delay, server computation capacity, and so on. The study shows that the vehicle voice cloud evaluation system can avoid complex communication and language processing, evaluate the performance of the service from view of end user.

Cerebral infarction causes severe social and economic burdens to patients due to its high morbidity and mortality rates, and the available treatments are limited. RO27-3225 is a highly selective melanocortin receptor 4 agonist that alleviates damage in many nervous system diseases, such as cerebral hemorrhage, traumatic brain injury and chronic neurodegenerative diseases. However, the effect of RO27-3225 on cerebral infarction remains unclear. In this study, we used a mouse model of transient middle cerebral artery occlusion (tMCAO) and administered RO27-3225 or saline to the mice through intraperitoneal injection. RO27-3225 increased the number of Nestin+/BrdU+ cells and doublecortin (DCX)+/BrdU+ cells in the subventricular zone (SVZ) and the number of DCX+/BrdU+ cells in the peri-infarct area on day 7 after tMCAO. Furthermore, RO27-3225 decreased the number of activated microglia (Iba1+ cells with a specific morphology) and the expression levels of Iba1, TNFα, IL6, and iNOS proteins and increased the number of PDGFRβ+ cells in the peri-infarct region on day 3 after tMCAO. Finally, RO27-3225-treated mice exhibited significantly decreased infarct volumes, brain water contents, and neurological deficits after cerebral infarction. Thus, RO27-3225 can improve the outcomes following cerebral infarction, partially by regulating neurogenesis in the SVZ, PDGFRβ+ cell survival and neuroinflammation in the peri-infarct zone. Our research reveals that RO27-3225 is a potential new treatment for cerebral infarction.

Neuroinflammation crucially influences functional recovery after ischemic stroke. Wnt-3a, a novel Wnt protein that specifically promotes Wnt/β-catenin signaling pathway, has been shown to regulate apoptosis and cell proliferation, but how it affects ischemic stroke-induced toxic brain inflammation remains unknown. Using a transient middle cerebral artery occlusion (tMCAO) mouse model in this study, we found that intranasal Wnt-3a-treated tMCAO mice had apparently reduced infarct volume and decreased brain water content after being allowed to recover for 72 h, as well as better neurologic outcomes on days 3, 7, and 14. Mice received Wnt-3a had significantly fewer tMCAO-induced peri-infarct TUNEL-positive cells compared with those received vehicle. Further, Wnt-3a-delivered tMCAO mice had notably fewer peri-infarct CD68-positive cells and lower ionized calcium-binding adapter molecule (Iba)-1 protein level. Wnt-3a significantly downregulated the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α, and upregulated the expression of arginase 1 (Arg1) and CD206. Finally, Wnt-3a obviously decreased the number of tMCAO-induced peri-infarct glial fibrillary acidic protein (GFAP)/C3-positive cells, increased the number of GFAP/S100A10-positive cells, attenuated the protein levels of GFAP and interleukin 15 (IL15), and elevated IL33 protein level. Our findings suggest that intranasal Wnt-3a could ameliorate toxic responses of microglia/macrophages and astrocytes in ischemic brain injury, supporting that Wnt-3a might be potentially appropriate for ischemic stroke treatment functioning as an immunomodulatory agent.

On the background of “Internet +” era, the domestic higher education is showing the trend of artificial intelligence. The reliability and scientificity of computer intelligent evaluation are further carried out, and the mode of intelligent evaluation and data analysis in optimizing the precise teaching of English writing is explored, which can lay a foundation for the large-scale use of the technology. Based on data-driven theory, this study further analyzed the role of AI in promoting in-depth learning by comparing AI writing review model with manual review model.

Background At low levels, carbon monoxide (CO) has been shown to have beneficial effects on multiple organs and tissues through its potential anti-inflammatory, anti-apoptotic, and anti-proliferative properties. However, the effect of CO-releasing molecule (CORM)-3, a water-soluble CORM, on ischemic stroke and its mechanism of action are still unclear. Methods We investigated the role of CORM-3 in the mouse model of transient middle cerebral artery occlusion (tMCAO). CORM-3 or saline was administered to mice by retro-orbital injection at the time of reperfusion after 1-h tMCAO or at 1 h after sham surgery. We assessed infarct volume and brain water content at 24 and 72 h after ischemia, blood-brain barrier permeability at 6 and 72 h after ischemia, and neurologic deficits on days 1, 3, 7, and 14. Results Among mice that underwent tMCAO, those that received CORM-3 had significantly smaller infarct volume and greater expression of neuronal nuclear antigen (NeuN) and microtubule-associated protein 2 than did saline-treated mice. CORM-3-treated mice had significantly fewer activated microglia in the peri-infarction zone than did control mice and exhibited downregulated expression of ionized calcium-binding adapter molecule (Iba)-1, tumor necrosis factor-α, and interleukin 1β. CORM-3-treated mice had significantly lower brain water content and enhanced neurologic outcomes on days 3, 7, and 14 post-tMCAO. Lastly, CORM-3 treatment reduced Evans blue leakage; increased expression of platelet-derived growth factor receptor-β, tight junction protein ZO-1, and matrix protein laminin; and decreased protein level of matrix metalloproteinase-9. Conclusion CORM-3 treatment at the time of reperfusion reduces ischemia-reperfusion-induced brain injury by suppressing neuroinflammation and alleviating blood-brain barrier disruption. Our data suggest that CORM-3 may provide an effective therapy for ischemic stroke.

To solve the problem of the dynamic variation of wave force diameter of pile foundation for offshore wind turbines, wave force and moment of large diameter pile foundation can be calculated. In this paper, simulation technique is used to calculate the wave force and moment of different large diameter pile foundation, and the base shear force and moment of the interval 20-degree phase angle are obtained by the base line of the pile. Under the action of a certain load, the complete stress variation of the pile foundation is obtained. According to the basic principle of diffraction theory, the process curve of large diameter pile, and analysis of wave force, diffraction force changes in a certain period of time interval. The results show that the wave after the large diameter pile formed around the vortex, large diameter pile base shear, and moment dynamic change is nonlinear in a complete cycle, the diameter of the pile increases by 0.5 m, and the wave force increases by about 5%, the results show that it provides certain reference value for the offshore pile foundation pile with large diameter primary site. Some significant results for practical application are discussed.

To solve the localization that VGA display system based on computer or ASIC lacks portability and modification,a novel VGA display system to display any characters and images was designed under PS/2 keyboard control,which is based on user custom kernel SOPC technology.In FPGA,a 32-bits NIOS Ⅱ hardcore was built,main program was compiled with C language,and a AVALON BUS was used to connect the external drive controller and basic PIO interface,combined with VGA controller which composed by VGA timing module and buffers,the software part was completed through the above.Hardware platform is consisted of basic hardware circuit,external memory chips,PS/2 keyboard,VGA interface and UART circuit.The system finally achieved the migration of SOPC kernel and function of displaying character and image on CRT monitor under PS/2 keyboard control.

A pair of fiber lasers with high output power and low quantum-defect at 1018 nm was demonstrated. These two 1018 nm fiber lasers were used as the source of Michelson cavity to show experimentally that a coherent beam combination of two Yb-doped double-cladding fiber lasers using all-fiber Michelson cavity technique was achieved. We obtained an output power of 55 W with a coherent combination efficiency of 90.2%, which is the highest output power that single-mode 1018 nm fiber lasers have obtained so far. Moreover, we proved that coherent beam combination by using Michelson cavity can achieve high power single-mode output of fiber laser.

A novel Symmetric Sparse Representation (SSR) method has been presented to solve the band selection problem in hyperspectral imagery (HSI) classification. The method assumes that the selected bands and the original HSI bands are sparsely represented by each other, i.e., symmetrically represented. The method formulates band selection into a famous problem of archetypal analysis and selects the representative bands by finding the archetypes in the minimal convex hull containing the HSI band points (i.e., one band corresponds to a band point in the high-dimensional feature space). Without any other parameter tuning work except the size of band subset, the SSR optimizes the band selection program using the block-coordinate descent scheme. Four state-of-the-art methods are utilized to make comparisons with the SSR on the Indian Pines and PaviaU HSI datasets. Experimental results illustrate that SSR outperforms all four methods in classification accuracies (i.e., Average Classification Accuracy (ACA) and Overall Classification Accuracy (OCA)) and three quantitative evaluation results (i.e., Average Information Entropy (AIE), Average Correlation Coefficient (ACC) and Average Relative Entropy (ARE)), whereas it takes the second shortest computational time. Therefore, the proposed SSR is a good alternative method for band selection of HSI classification in realistic applications.

In order to guarantee the normal operation of marine, an effective fault diagnosis model need to be established to determine the reason causing the fault of marine diesel engine. According to the problem of fault diagnosis of marine diesel engine, by using the methods of kernel fisher discriminant analysis, a method solving fault diagnosis of marine diesel engine is proposed. Firstly, kernel fisher discriminant analysis was done to the historical fault set and the parameters were determined by grid method. In this way, the fault diagnosis model of marine diesel engine was built. Then, this model was used to diagnosis the actual fault of marine diesel engine. The effect of fault diagnosis in fuel injection system of MAN B&W 10L90MC marine diesel engine verified the effectiveness of this method. Therefore, the method proposed by this paper has certain practical significance towards the fault diagnosis of marine diesel engine.

Dual-wavelength laser at 532 nm and 660 nm are covert from fundamental laser generated at 1 064 nm and 1 319 nm by single Nd∶YAG crystal rod.On the basis of 1 064 nm and 1 319 nm dual-wavelength laser acquirsition,the second harmonic wave at 532 nm and 660 nm can be achieved by using non-linear frequency conversion technology.The output power of 1 064 nm and 1 319 nm laser are 30.5 W and 8.78 W simultaneously,35.6 W and 11.2 W respectively.The output power of 532 nm and 660 nm laser are 5.34 W and 1.353 W at 10.5 kHz and 20.5 kHz simultaneously,6.72 W and 1.90 W respectively.The frequency-doubling conversion efficiency are 17.5% and 15.4% in the two condition mentioned above.The instability is less than 2%.

Owing to damage, thermal issues, and nonlinear optical effects, the output power of fiber laser has been proven to be limited. Beam combining techniques are the attractive solutions in order to achieve high-power high-brightness fiber laser output. Designing such a high-power laser system relies on coherent and incoherent combination of radiation from multiple laser channels into a single beam with enhanced brightness. Spectral beam combination is a promising alternative way that allows each array to be overlapped in near-and far-field without spatial interference, thus relaxing the requirements for linewidth controlling and phase locking of individual array and practically allowing power and brightness to be scaled with the potential to combine a large number of channels. Spectral beam combination implementations can be divided into two subsets: serial and parallel, based on the combining elements. For scaling high power, we pursue spectral beam combining with parallel subsets as an alternative to other beam combination implementation. In the spectral beam combining system based on multi-layer dielectric grating, the combined beam suffers the degradation in beam quality, which is caused by the optical dispersion, and also by the random error due to the misalignment of arrays or the thermal-optic effect of grating in the experimental system. In this paper, we strictly derive the equation of M2 variation caused by the optical dispersion in both single-grating structure and dual-grating structure. And also, we discuss how the laser linewidth, beam size, spectral separation of two adjacent channels, distance between two adjacent channels and the period of grating influence the desired beam quality in detail, separately, in the single-grating structure and the dual-grating structure. The results show that with the value of M2 fixed, the finite beam size gives rise to a laser bandwidth decreasing in single-grating structure combination, whereas the beam size induces a laser bandwidth to increase in dual-grating structure combination. If M2 1.2, the laser bandwidth of dual-grating system can be over several sub-nanometers, rather than several tens of pm as in the single grating design.

We show experimentally that a tandem-pumped Yb-doped fiber amplifier with high power and low quantum-defect can be reached. And a high power 21 W output power at 1018 nm is demonstrated finally. We use this 1018 nm fiber laser as a pumping source of the 1080 nm fiber laser to demonstrate the tandem-pumped double-cladding Yb-doped fiber amplifier, and obtain an output power of 18.6 W at 1080 nm with a slope efficiency of 90.86%.