Lipopolysaccharide restricts murine norovirus infection in macrophages mainly through NF-kB and JAK-STAT signaling pathway

The inflammasome machinery has recently been recognized as an emerging pillar of innate immunity. However, little is known regarding the interaction between the classical interferon (IFN) response and inflammasome activation in response to norovirus infection. We found that murine norovirus (MNV-1) infection induces the transcription of IL-1β, a hallmark of inflammasome activation, which is further increased by inhibition of IFN response, but fails to trigger the release of mature IL-1β. Interestingly, pharmacological inflammasome inhibitors do not affect viral replication, but slightly reverse the inflammasome activator lipopolysaccharide (LPS)-mediated inhibition of MNV replication. LPS efficiently stimulates the transcription of IFN-β through NF-ĸB, which requires the transcription factors IRF3 and IRF7. This activates downstream antiviral IFN-stimulated genes (ISGs) via the JAK-STAT pathway. Moreover, inhibition of NF-ĸB and JAK-STAT signaling partially reverse LPS-mediated anti-MNV activity, suggesting additional antiviral mechanisms activated by NF-ĸB. This study reveals additional insight in host defense against MNV infection

Systematically comparing COVID-19 with the 2009 influenza pandemic for hospitalized patients

Objectives: This study aimed to comprehensively compare the clinical features of hospitalized COVID-19 patients with hospitalized 2009 influenza pandemic patients. Methods: Medline, Embase, Web of Science, Cochrane CENTRAL, and Google scholar were systematically searched to identify studies related to COVID-19 and the 2009 influenza pandemic. The pooled incidence rates of clinical features were estimated using the DerSimonian-Laird random-effects model with the Freeman-Tukey double arcsine transformation method. Results: The incidence rates of fever, cough, shortness of breath, sore throat, rhinorrhea, myalgia/muscle pain, or vomiting were found to be significantly higher in influenza patients when compared with COVID-19 patients. The incidence rates of comorbidities, including cardiovascular disease/hypertension and diabetes, were significantly higher in COVID-19 compared with influenza patients. In contrast, comorbidities such as asthma, chronic obstructive pulmonary disease, and immunocompromised conditions were significantly more common in influenza compared with COVID-19 patients. Unexpectedly, the estimated rates of intensive care unit admission, treatment with extracorporeal membrane oxygenation, treatment with antibiotics, and fatality were comparable between hospitalized COVID-19 and 2009 influenza pandemic patients. Conclusions: This study comprehensively estimated the differences and similarities of the clinical features and burdens of hospitalized COVID-19 and 2009 influenza pandemic patients. This information will be important to better understand the current COVID-19 pandemic

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

Current management of intracerebral haemorrhage in China: a national, multi-centre, hospital register study

<p>Abstract</p> <p>Background</p> <p>We aimed to examine current practice of the management and secondary prevention of intracerebral haemorrhage (ICH) in China where the disease is more common than in Western populations.</p> <p>Methods</p> <p>Data on baseline characteristics, management in-hospital and post-stroke, and outcome of ICH patients are from the ChinaQUEST (QUality Evaluation of Stroke Care and Treatment) study, a multi-centre, prospective, 62 hospital registry in China during 2006-07.</p> <p>Results</p> <p>Nearly all ICH patients (n = 1572) received an intravenous haemodiluting agent such as mannitol (96%) or a neuroprotectant (72%), and there was high use of intravenous traditional Chinese medicine (TCM) (42%). Neurosurgery was undertaken in 137 (9%) patients; being overweight, having a low Glasgow Coma Scale (GCS) score on admission, and Total Anterior Circulation Syndrome (TACS) clinical pattern on admission, were the only baseline factors associated with this intervention in multivariate analyses. Neurosurgery was associated with nearly three times higher risk of death/disability at 3 months post-stroke (odd ratio [OR] 2.60, p < 0.001). Continuation of antihypertensives in-hospital and at 3 and 12 months post-stroke was reported in 732/935 (78%), 775/935 (83%), and 752/935 (80%) living patients with hypertension, respectively.</p> <p>Conclusions</p> <p>The management of ICH in China is characterised by high rates of use of intravenous haemodiluting agents, neuroprotectants, and TCM, and of antihypertensives for secondary prevention. The controversial efficacy of these therapies, coupled with the current lack of treatments of proven benefit, is a call for action for more outcomes based research in ICH.</p

Urban Form Energy Use and Emissions in China: Preliminary Findings and Model Proof of Concept

Urbanization is reshaping China's economy, society, and energy system. Between 1990 and 2008 China added more than 300 million new urban residents, bringing the total urbanization rate to 46%. The ongoing population shift is spurring energy demand for new construction, as well as additional residential use with the replacement of rural biomass by urban commercial energy services. This project developed a modeling tool to quantify the full energy consequences of a particular form of urban residential development in order to identify energy- and carbon-efficient modes of neighborhood-level development and help mitigate resource and environmental implications of swelling cities. LBNL developed an integrated modeling tool that combines process-based lifecycle assessment with agent-based building operational energy use, personal transport, and consumption modeling. The lifecycle assessment approach was used to quantify energy and carbon emissions embodied in building materials production, construction, maintenance, and demolition. To provide more comprehensive analysis, LBNL developed an agent-based model as described below. The model was applied to LuJing, a residential development in Jinan, Shandong Province, to provide a case study and model proof of concept. This study produced results data that are unique by virtue of their scale, scope and type. Whereas most existing literature focuses on building-, city-, or national-level analysis, this study covers multi-building neighborhood-scale development. Likewise, while most existing studies focus exclusively on building operational energy use, this study also includes embodied energy related to personal consumption and buildings. Within the boundaries of this analysis, food is the single largest category of the building energy footprint, accounting for 23% of the total. On a policy level, the LCA approach can be useful for quantifying the energy and environmental benefits of longer average building lifespans. In addition to prospective analysis for standards and certification, urban form modeling can also be useful in calculating or verifying ex post facto, bottom-up carbon emissions inventories. Emissions inventories provide a benchmark for evaluating future outcomes and scenarios as well as an empirical basis for valuing low-carbon technologies. By highlighting the embodied energy and emissions of building materials, the LCA approach can also be used to identify the most intensive aspects of industrial production and the supply chain. The agent based modeling aspect of the model can be useful for understanding how policy incentives can impact individual behavior and the aggregate effects thereof. The most useful elaboration of the urban form assessment model would be to further generalize it for comparative analysis. Scenario analysis could be used for benchmarking and identification of policy priorities. If the model is to be used for inventories, it is important to disaggregate the energy use data for more accurate emissions modeling. Depending on the policy integration of the model, it may be useful to incorporate occupancy data for per-capita results. On the question of density and efficiency, it may also be useful to integrate a more explicit spatial scaling mechanism for modeling neighborhood and city-level energy use and emissions, i.e. to account for scaling effects in public infrastructure and transportation

A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Background High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ −6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. Methods The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. Findings In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17–21%), 2% (1–3%), 8% (7–10%) and 6% (3–9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75–0.81), 0.58 (0.53–0.64), 0.71 (0.69–0.74) and 0.67 (0.62–0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92–1.24). Interpretation Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted fo

Investigation of the stress and strain state of clay pipes under fire condition

The focus of this paper is given to investigating the testing and evaluation method of stress and deformation behaviour of clay pipe elements like chimneys under cyclic high temperature. The experimental study on the temperature–time curves and on the radial deformation–temperature curves of a series of fire-resistant clay pipes was carried out. The tensile strength and the compressive strength, the elastic modulus before and after fire, the stress and deformation properties and the cracking behaviour of the clay pipes under fire conditions have been analyzed. The theoretical analysis corresponds well with the experimental results and tends to prove that the elastic deformation can be the most significant component in fixed-end clay pipes. This study is useful for evaluation of the stress–strain properties of ceramic pipes and provides a beneficial test method for the pipe member in small-scale or in full-scale tests under fire temperatures.Chinese National Science Foundatio

Mesoporous Silica Gel–Based Mixed Matrix Membranes for Improving Mass Transfer in Forward Osmosis: Effect of Pore Size of Filler

The efficiency of forward osmosis (FO) process is generally limited by the internal concentration polarization (ICP) of solutes inside its porous substrate. In this study, mesoporous silica gel (SG) with nominal pore size ranging from 4–30 nm was used as fillers to prepare SG-based mixed matrix substrates. The resulting mixed matrix membranes had significantly reduced structural parameter and enhanced membrane water permeability as a result of the improved surface porosity of the substrates. An optimal filler pore size of ~9 nm was observed. This is in direct contrast to the case of thin film nanocomposite membranes, where microporous nanoparticle fillers are loaded to the membrane rejection layer and are designed in such a way that these fillers are able to retain solutes while allowing water to permeate through them. In the current study, the mesoporous fillers are designed as channels to both water and solute molecules. FO performance was enhanced at increasing filler pore size up to 9 nm due to the lower hydraulic resistance of the fillers. Nevertheless, further increasing filler pore size to 30 nm was accompanied with reduced FO efficiency, which can be attributed to the intrusion of polymer dope into the filler pores.MOE (Min. of Education, S’pore)Published versio