Compression Behaviour of Natural and Reconstituted Clays

International audienceThe intercept of the log(1+e) - logσv' straight line is introduced to describe the effect of the starting point on the compressibility of natural and reconstituted clays. It is found that when the effective stress exceeds the remoulded yield stress, the compression behaviour of reconstituted clays is controlled solely by the water content at the remoulded yield stress and the liquid limit. Comparison of the compression behaviour of natural and reconstituted clays indicates that their difference in compressibility is caused by soil structure and the difference in water content at the compression starting point. The compression behaviour of natural clays can be classified into three regimes: 1) the pre-yield regime characterised by small compressibility with soil structure restraining the deformation up to the consolidation yield stress; 2) the transitional regime characterised by a gradual loss of soil structure when the effective stress is between the consolidation yield stress and the transitional stress; and 3) the post-transitional regime characterised by the same change law in compression behaviour as reconstituted clays when the effective stress is higher than the transitional stress. For the investigated clays, the transitional stress is 1.0-3.5 times the consolidation yield stress. The compression index varies solely with the void ratio at an effective stress of 1.0 kPa for both natural clays in post-transitional regime and reconstituted clays when the effective stress exceeds the remoulded yield stress, and when compressed in such cases the compression curves of both natural clays and reconstituted clays can be normalised well to a unique line using the void index

Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020

Nrf2 Deficiency Exacerbated CLP-Induced Pulmonary Injury and Inflammation through Autophagy- and NF-κB/PPARγ-Mediated Macrophage Polarization

The balance between M1 and M2 macrophage polarization is involved in the regulation of pulmonary inflammation. Nuclear factor erythroid-derived 2-like 2 (Nfe2l2, also known as Nrf2), a nuclear transcription factor, is reported to play protective roles in acute lung injury (ALI) and inflammation, and increasing evidence indicates that the protective effects of Nrf2 are closely related to autophagy. This study aimed to explore whether Nrf2 is involved in sepsis-induced acute pulmonary injury and inflammation and in the role of macrophage polarization in the process. In the present study, sepsis patients, an Nrf2 knockout mouse that underwent cecal ligation and puncture (CLP), and lipopolysaccharide (LPS)-treated macrophage cell lines were employed to investigate the potential functions of Nrf2 in sepsis-induced lung injury and the underlying mechanisms. Clinical studies showed that the NRF2 mRNA level was inversely correlated with pulmonary inflammation and disease severity in patients with sepsis. Analyses in a CLP-treated Nrf2 knockout mouse model indicated that an Nrf2 deficiency promoted a CLP-induced increase in M1 macrophage polarization and apoptosis and inhibited CLP-induced upregulation of the autophagy level in lung tissues. Experiments in RAW264.7 cells revealed that Nrf2 overexpression inhibited M1 macrophage polarization but promoted M2 macrophage polarization by improving the autophagy, and Nrf2 overexpression promoted PPARγ but inhibited NF-κB nuclear translocation. In conclusion, these results indicate that Nrf2 plays a protective role in sepsis-induced pulmonary injury and inflammation through the regulation of autophagy- and NF-κB/PPARγ-mediated macrophage polarization

Surgical Masks for Protection of Health Care Personnel Against Covid-19: Results from an Observational Study

Purpose: The aim of the study was to describe the use of masks among health care personnel (HCP) exposed to index cases of coronavirus disease 2019 (COVID-19), and to evaluate any association with infection rate. Methods: We did a retrospective, observational study of HCP at Zhongnan Hospital of Wuhan University for the management of COVID-19 (before person-to-person transmission was official confirmed, no additional protection was provided). A questionnaire was given to all staff listed on the roster in the clinical regions providing care for index patients with COVID-19. All participants were surveyed regarding hand-washing and use of surgical masks and gloves and were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were analysed (Student’s t test and Pearson χ2 test) for an association between infection and use of personal protective equipment. Results: Exposure of a total of 299 non-infected and 30 infected staff was confirmed. None of the 149 staff who reported use of all three preventative measures (hand-washing and use of gloves and masks) became infect-ed. In contrast, all 30 of the staff who became infected had omitted at least one of the measures. Fewer staff who wore surgical masks (P=0.000003) became infected compared with those who did not. Infections rates were significantly lower in HCP from the internal medicine departments, as these personnel generally wore masks. Conclusion: An association was found between SARS-CoV-2 infection of HCP and the non-use of masks when working with index cases in clinical settings. We recommend that all HCP follow the strict instructions for prevention and treatment of nosocomial infection during intimate contact with COVID-19, especially staff from surgical departments

Bhlhe40 deficiency attenuates LPS-induced acute lung injury through preventing macrophage pyroptosis

Abstract Background Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. Recently, increasing evidence supports activated inflammation and gasdermin D (GSDMD)-mediated pyroptosis in macrophage are closely associated with ALI. Basic helix-loop-helix family member e40 (Bhlhe40) is a transcription factor that is comprehensively involved in inflammation. However, there is little experimental evidence connecting Bhlhe40 and GSDMD-driven pyroptosis. The study sought to verify the hypothesis that Bhlhe40 is required for GSDMD-mediated pyroptosis in lipopolysaccharide (LPS)-induced inflammatory injury. Method We performed studies using Bhlhe40-knockout (Bhlhe40 −/−) mice, small interfering RNA (siRNA) targeting Bhlhe40 and pyroptosis inhibitor disulfiram to investigate the potential roles of Bhlhe40 on LPS-induced ALI and the underlying mechanisms. Results Bhlhe40 was highly expressed in total lung tissues and macrophages of LPS-induced mice. Bhlhe40 −/− mice showed alleviative lung pathological injury and inflammatory response upon LPS stimulation. Meanwhile, we found that Bhlhe40 deficiency significantly suppressed GSDMD-mediated pyroptosis in macrophage in vivo and in vitro. By further mechanistic analysis, we demonstrated that Bhlhe40 deficiency inhibited GSDMD-mediated pyroptosis and subsequent ALI by repressing canonical (caspase-1-mediated) and non-canonical (caspase-11-mediated) signaling pathways in vivo and in vitro. Conclusion These results indicate Bhlhe40 is required for LPS-induced ALI. Bhlhe40 deficiency can inhibit GSDMD-mediated pyroptosis and therefore alleviate ALI. Targeting Bhlhe40 may be a potential therapeutic strategy for LPS-induced ALI

Additional file 1 of Bhlhe40 deficiency attenuates LPS-induced acute lung injury through preventing macrophage pyroptosis

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