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Early neurologic improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue based on a prospective cohort. In INTRECIS study, five centers were designed to consecutively collect blood sample from enrolled patients. The patients with ENI and without ENI were matched by propensity score matching with a ratio of 1:1. Preset 49 biomarkers were measured through microarray analysis. Enrichment of gene ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers. Of 358 patients, 19 patients with ENI were assigned to ENI group, while 19 matched patients without ENI were assigned to Non ENI group. A total of nine biomarkers were found different between two groups, in which serum levels of chemokine (C-C motif) ligand (CCL)-23, chemokine (C-X-C motif) ligand (CXCL)-12, insulin-like growth factor binding protein (IGFBP)-6, interleukin (IL)-5, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, plasminogen activator inhibitor (PAI)-1, platelet-derived growth factor (PDGF)-AA, suppression of tumorigenicity (ST)-2, and tumor necrosis factor (TNF)-α were higher in the ENI group, compared with those in the Non ENI group. We found that serum levels of CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α at admission were associated with post-thrombolytic ENI in stroke. The role of biomarkers warrants further investigation. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT02854592.

Background Early neurologic improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue based on a prospective cohort. Methods In INTRECIS study, five centers were designed to consecutively collect blood sample from enrolled patients. The patients with ENI and without ENI were matched by propensity score matching with a ratio of 1:1. Preset 49 biomarkers were measured through microarray analysis. Enrichment of gene ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers. Results Of 358 patients, 19 patients with ENI were assigned to ENI group, while 19 matched patients without ENI were assigned to Non ENI group. A total of nine biomarkers were found different between two groups, in which serum levels of chemokine (C-C motif) ligand (CCL)-23, chemokine (C-X-C motif) ligand (CXCL)-12, insulin-like growth factor binding protein (IGFBP)-6, interleukin (IL)-5, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, plasminogen activator inhibitor (PAI)-1, platelet-derived growth factor (PDGF)-AA, suppression of tumorigenicity (ST)-2, and tumor necrosis factor (TNF)-α were higher in the ENI group, compared with those in the Non ENI group. Conclusions We found that serum levels of CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α at admission were associated with post-thrombolytic ENI in stroke. The role of biomarkers warrants further investigation. Trial registration Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT02854592.

Two vital functions of the innate immune system are to initiate inflammation and redistribute micronutrients in favor of the host. Zinc is an essential micronutrient used in host defense. The zinc importer ZIP8 is uniquely induced through stimulation of the NF-κB pathway by LPS in monocytes and functions to regulate inflammation in a zinc-dependent manner. Herein we determined the impact of zinc metabolism following LPS-induced inflammation in human macrophages. We observed that ZIP8 is constitutively expressed in resting macrophages and strikingly elevated following LPS exposure, a response that is unique compared to the 13 other known zinc import proteins. During LPS exposure, extracellular zinc concentrations within the physiological range markedly reduced IL-10 mRNA expression and protein release but increased mRNA expression of TNFα, IL-8, and IL-6. ZIP8 knockdown inhibited LPS-driven cellular accumulation of zinc and prevented zinc-dependent reduction of IL-10 release. Further, zinc supplementation reduced nuclear localization and activity of C/EBPβ, a transcription factor known to drive IL-10 expression. These studies demonstrate for the first time that zinc regulates LPS-mediated immune activation of human macrophages in a ZIP8-dependent manner, reducing IL-10. Based on these findings we predict that macrophage zinc metabolism is important in host defense against pathogens.

This paper analyzes the relevant factor which influences the accident severity, and puts forward BP neural network traffic accident serious level model based on principal component analysis, it selects the main causes and accident serious level of 344 traffic accidents in Harbin in 2003 on the main road as the training and binding of the model, make sure that there is a good correspondence between the related main causes and the serious level. The model provides reference for the main control factors in order to determine the serious level of road traffic accidents of Nonlinear Systems.

Collaborative product design is a multiple criteria group decision making process bringing different and often controversial points of view together to create a solution among stakeholders. Collaborative design possesses more perspectives than any single person possesses because stakeholders have different perspectives. This work is based on new decision approach that includes creating shared understanding among various stakeholders, contextualizing design criteria and perspectives, and creating a multiple perspective and multiple criteria decision approach, our initial effort has focused on incorporating perspectives into design process. We then provide the approach to find the optimal design decisions for consideration of stakeholders’ perspectives. By analyzing the relationships between stakeholders’ perspectives and preferences of design criteria, multi-criteria decision making approach considering the stakeholders’ perspectives can be used to monitor and control the collaborative design process.

The recent advance in information technologies has the potential to greatly enhance product development, and to make distributed designers, engineers, manufacturers and customers work together over networks. This paper reviews related work on service-oriented architecture, distributed infrastructure and highlights the need to integrate service-oriented architecture technologies for meaningful and interactive collaborative design processes. This paper presents a service-oriented architecture implemented by web services for collaborative design. The collaborative workspace is presented to facilitate the design participants’ collaboration. The proposed architecture is applicable to different requirements of design participants and enhances design interaction during the product realization process.

The role of Fat Mass and Obesity-associated protein （FTO） and its substrate N6-methyladenosine （m6A） in mRNA processing and adipogenesis remains largely unknown. We show that FTO expression and m6A levels are inversely correlated during adipogenesis. FTO depletion blocks differentiation and only catalytically active FTO restores adi- pogenesis. Transcriptome analyses in combination with m6A-seq revealed that gene expression and mRNA splicing of grouped genes are regulated by FTO. M6A is enriched in exonic regions flanking 5＇- and 3＇-splice sites, spatially over- lapping with mRNA splicing regulatory serine/arginine-rich （SR） protein exonic splicing enhancer binding regions. Enhanced levels of m6A in response to FTO depletion promotes the RNA binding ability of SRSF2 protein, leading to increased inclusion of target exons. FTO controls exonic splicing of adipogenie regulatory factor RUNX1T1 by regulating m6A levels around splice sites and thereby modulates differentiation. These findings provide compelling evidence that FTO-dependent m6A demethylation functions as a novel regulatory mechanism of RNA processing and plays a critical role in the regulation of adipogenesis.

As a renewable and environment-friendly technology for seawater desalination and wastewater purification, solar energy triggered steam generation is attractive to address the long-standing global water scarcity issues. However, practical utilization of solar energy for steam generation is severely restricted by the complex synthesis, low energy conversion efficiency, insufficient solar spectrum absorption and water extraction capability of state-of-the-art technologies. Here, for the first time, we report a facile strategy to realize hydrogen bond induced self-assembly of a polydopamine (PDA)@MXene microsphere photothermal layer for synergistically achieving wide-spectrum and highly efficient solar absorption capability (≈ 96% in a wide solar spectrum range of 250–1,500 nm wavelength). Moreover, such a system renders fast water transport and vapor escaping due to the intrinsically hydrophilic nature of both MXene and PDA, as well as the interspacing between core-shell microspheres. The solar-to-vapor conversion efficiencies under the solar illumination of 1 sun and 4 sun are as high as 85.2% and 93.6%, respectively. Besides, the PDA@MXene photothermal layer renders the system durable mechanical properties, allowing producing clean water from seawater with the salt rejection rate beyond 99%. Furthermore, stable light absorption performance can be achieved and well maintained due to the formation of ternary TiO2/C/MXene complex caused by oxidative degradation of MXene. Therefore, this work proposes an attractive MXene-assisted strategy for fabricating high performance photothermal composites for advanced solar-driven seawater desalination applications.

The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.

The light-matter interaction between plasmonic nanocavity and exciton at the sub-diffraction limit is a central research field in nanophotonics. Here, we demonstrated the vertical distribution of the light-matter interactions at ~1 nm spatial resolution by coupling A excitons of MoS2 and gap-mode plasmonic nanocavities. Moreover, we observed the significant photoluminescence (PL) enhancement factor reaching up to 2800 times, which is attributed to the Purcell effect and large local density of states in gap-mode plasmonic nanocavities. Meanwhile, the theoretical calculations are well reproduced and support the experimental results.The plasmon-exciton interaction between gap-mode nanocavities and A excitons of MoS2 is investigated, and the longitudinal distribution of the plasmon-exciton interactions is obtained at ~1 nm spatial resolution.