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In clinical settings, physicians tend to use corticosteroids in the most critically ill patients. [...]selection bias and confounders in observational studies might contribute to any observed increased mortality in patient groups treated with corticosteroids. Inconclusive clinical evidence should not be a reason for abandoning corticosteroid use in 2019-nCoV pneumonia. [...]there are studies supporting the use of corticosteroids at low-to-moderate dose in patients with coronavirus infection. According to the expert consensus statement, the following basic principles should be followed when using corticosteroids: (1) the benefits and harms should be carefully weighed before using corticosteroids; (2) corticosteroids should be used prudently in critically ill patients with 2019-nCoV pneumonia; (3) for patients with hypoxaemia due to underlying diseases or who regularly use corticosteroids for chronic diseases, further use of corticosteroids should be cautious; and (4) the dosage should be low-to-moderate (≤0·5–1 mg/kg per day methylprednisolone or equivalent) and the duration should be short (≤7 days).

Macrophages, with diverse functions and variable phenotypes, are considered as an important executor of inflammatory diseases. And it has been proved that autophagy is deeply connected with the development of inflammation, while the exact regulatory mechanism still remains unclear, and the application of autophagy regulators in anti-inflammation needs to be further confirmed. Here, we firstly verified that neochromine S5 (hereinafter referred to as S5) significantly inhibited M1-like macrophage polarization with decrease of the proinflammatory cytokines and downregulation of NF-κB and STAT1 signals. Then, in vivo experiments demonstrated S5 improved cecal ligation and puncture (CLP)-induced sepsis specially based on the regulation of M1-like macrophages. Mechanistic studies indicated that S5 treatment dramatically upregulated cellular autophagy in M1-like macrophage. Furthermore, by multiple methods, S5 was revealed to directly bind with ubiquitin-specific proteases 14 (USP14) at Ser404, Phe405, and Cys414 by hydrogen bond to inhibit its deubiquitinating activity, and block USP14–TRAF6 (TNF receptor associated factor 6) interaction, subsequently promoting ubiquitination of Beclin1, interrupting Beclin1–Bcl2 interaction, and accumulating the autophagosome in macrophages, which finally resulted in the blockade of M1-like macrophage polarization. Animal experiments also confirmed the protection of S5 in CLP mice was dependent on activation of macrophage autophagy. What’s more, as a novel USP14 inhibitor, S5 exhibited higher efficiency and safety than IU1, the known USP14 inhibitor. Therefore, this study has demonstrated that typically inhibiting USP14 promotes autophagy in M1-like macrophages and alleviates CLP-induced sepsis. Moreover, we provide a new candidate compound, S5, for sensitizing autophagy to interfere with the macrophage inflammation.

Autophagy and NLRP3 inflammasome were associated with the process of colitis. Drugs targeting NLRP3 inflammasome and autophagy to treat colitis are absent, and they are urgently required. Herein, we examine the effect of evodiamine, extracted from the fruit of Evodiae Fructus , on experimental colitis induced by dextran sulfate sodium and exposit whether evodiamine effects on autophagy and NLRP3 inflammasome. Our data indicated that colitis was ameliorated by evodiamine, including the improvement of mice body weight, colon length, histopathologic score, and the disease activity index. We also observed that evodiamine restrained the formation of the NLRP3 inflammasome by inhibiting the apoptosis-associated speck-like protein oligomerization and caspase-1 activity in THP-1 macrophages. Our results demonstrated evodiamine inhibit NLRP3 inflammasome activation via the induction of autophagosome-mediated degradation of inflammasome and the inhibition of NFκB pathway, which synergistically contribute to the effect of evodiamine in colitis. It indicates the potential use of evodiamine in inflammatory bowel diseases treatment.

Acute liver injury (ALI), often caused by viruses, alcohol, drugs, etc., is one of the most common clinical liver diseases. Although pyroptosis plays an important role in ALI, there is still a lack of effective clinical drugs related to this mechanism. Here, we show that phenethyl isothiocyanate (PEITC), a natural compound present in cruciferous vegetables, can significantly alleviate concanavalin A (ConA)-induced inflammatory liver damage and carbon tetrachloride (CCl 4 )-induced chemical liver damage in a dose-dependent manner. PEITC dose-dependently reversed the ALI-induced increase in plasma levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interferon (IFN)-γ and reduced the protein levels of hepatocyte pyroptosis markers such as Nod-like receptor family pyrin domain containing 3 (NLRP3), cleaved caspase-1, and cleaved gasdermin D (GSDMD). In vitro experiments have also verified the inhibitory effect of PEITC on hepatocyte pyroptosis. Furthermore, PEITC inhibits pyroptosis by interacting with cysteine 191 of GSDMD. In summary, our findings establish a role for PEITC in rescuing hepatocyte pyroptosis via direct inhibition of GSDMD, which may provide a new potential therapeutic strategy for ALI.

The spread of grape leaf diseases has a negative impact on the sustainable development of agriculture. Diseases induced by Uncinula necator significantly affect the quality of grapes. Bacillus biocontrol agents have been proven effective in disease management. However, limited research has been conducted on the impact of biocontrol agents on the assembly and potential functions of plant phyllosphere microbial communities. This study used high-throughput sequencing combined with bioinformatics analysis and culture omics technology for analysis. The results showed that biocontrol bacteria B. subtilis utilized in this study can significantly reduce the disease index of powdery mildew ( p <0.05); concurrently, it exhibits a lower disease index compared to traditional fungicides. A comprehensive analysis has revealed that biocontrol bacteria have no significant impact on the diversity of phyllosphere fungi and bacteria, while fungicides can significantly reduce bacterial diversity. Additionally, biocontrol agents can increase the complexity of fungal networks and enhance the degree of modularity and stability of the bacterial network. The results also showed that the biocontrol agents, which contained a high amount of B. subtilis , were able to effectively colonize the grapevine phyllosphere, creating a microenvironment that significantly inhibits pathogenic bacteria on grape leaves while enhancing leaf photosynthetic capacity. In conclusion, biocontrol agents significantly reduce the grape powdery mildew disease index, promote a microenvironment conducive to symbiotic microorganisms and beneficial bacteria, and enhance plant photosynthetic capacity. These findings provide a basis for promoting biocontrol agents and offer valuable insights into sustainable agriculture development.

Immobilized microbial technology has recently emerged as a prominent research focus for the remediation of heavy metal pollution because of its superior treatment efficiency, ease of operation, environmental friendliness, and cost-effectiveness. This study investigated the adsorption characteristics and mechanisms of Cd2+ solutions by Lactobacillus plantarum adsorbed immobilized on distiller’s grains biochar (XIM) and Lactobacillus plantarum–encapsulated immobilized on distiller’s grains biochar (BIM). The findings reveal that the maximum adsorption capacity and efficiency were achieved at a pH solution of 6.0. Specifically, at an adsorption equilibrium concentration of cadmium at 60 mg/L, XIM and BIM had adsorption capacities of 8.40 ± 0.30 mg/g and 12.23 ± 0.05 mg/g, respectively. BIM demonstrated noticeably greater adsorption capacities than XIM at various cadmium solution concentrations. A combination of isothermal adsorption modeling, kinetic modeling, scanning electron microscopy–energy dispersive X-ray spectroscopy, X-ray diffractometer (XRD), and Fourier-transform infrared spectroscopy (FTIR) analyses showed that cadmium adsorption by XIM primarily involved physical adsorption and pore retention. In contrast, the adsorption mechanism of BIM was mainly attributed to the formation of Cd(CN)2 crystals.

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 30 th 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 6 th February 2020. Trial registration ClinicalTrials.gov : NCT04257656. Registered on 6 February 2020.

Introduction Carbon monoxide (CO) released from CORM-2 has anti-inflammatory function, but the critical molecule mediating the inflammation inhibition has not been elucidated. Previous studies indicate that CORM-2 can activate Nrf2, a key transcription factor regulating host defense against oxidative stress and inflammation-related disorders. In this study we use Nrf2 knockout mice to determine the role of Nrf2 in mediating the CO anti-inflammatory action. Methods We compared CORM-2’s inhibiting effect on pro-inflammatory cytokine expressions (TNF-α, IL-1β and IL-6 and iNOS) in primary peritoneal macrophages, mouse liver and brain tissues from Nrf2 +/+ and Nrf2 −/− mice. We further assayed the inflammatory cell infiltration in both liver and brain tissues of the Nrf2 +/+ and Nrf2 −/− mice. Finally, we examined CORM’s influence on mouse mortality in a mouse sepsis model. Results Our results showed that CORM-2 dramatically inhibited the expression of pro-inflammatory cytokines in Nrf2 +/+ mice, but not in Nrf2 −/− mice. Furthermore CORM-2 substantially decreased LPS-induced mouse mortality of Nrf2 +/+ mice, but not of Nrf2 −/− mice. Conclusion We conclude that Nrf2 is indispensable for CORM-2 inhibition of LPS-induced inflammation.

Background This study evaluated the effects of black tea drinks with inulin and dextrin (BTID) on postprandial plasma glucose (PG) in patients with type 2 diabetes mellitus (T2DM). Methods An acute, randomized, double-blind, placebo-controlled, crossover clinical trial was carried out on T2DM patients. The subjects were randomly assigned to groups consuming placebo black tea powder or BTID (identically packaged) followed by a mixed meal tolerance test (MMTT). Afterwards, individuals who initially consumed BTID were given the placebo and those who initially consumed the placebo were given BTID. Results A total of 35 patients were included in the study, and 32 completed the study. Compared to placebo, BTID significantly reduced the change in glycaemia at 30 min, 1, 2, and 3 h during the MMTT. In the analysis of PG fluctuations at 2 h during the MMTT, the proportion of patients with minor PG fluctuations (< 2.8 mmol/L) in the BTID group was 53.1%, significantly higher than the 28.1% in the placebo group. Binary logistic regression analysis revealed that the risk of significant PG fluctuations decreased by 65.5% after consuming BTID, with a corresponding odds ratio of 0.345 ( P  = 0.044, 95% CI 0.122–0.974). In addition, the areas under the curve for PG and insulin secretion after BTID administration were significantly smaller than that for placebo. Conclusions Compared to placebo, BTID significantly reduced the change in PG levels during the MMTT and decreased the risk of large PG fluctuations by 65.5%. These effects were associated to a significant reduction in postprandial insulin secretion and may help to improved insulin sensitivity and a lower β-cell burden.

Aiming to clarify the effect of Lactobacillus plantarum combined with distiller's grains biochar on lead, cadmium and zinc complex contaminated soil, a pot experiment was conducted to investigate soil effective heavy metal concentration, plant growth, and heavy metal accumulation in the Sorghum hybrid sudangrass. The results revealed that single application of distiller's grains biochar, Lactobacillus plantarum thallus, Lactobacillus plantarum supernatant, and combined application of distiller's grain biochar and Lactobacillus plantarum thallus could significantly reduce the content of available Cd, Pb, and Zn in soil (P<0.05), and reduced the aboved metals content in the aerial parts and roots of Sorghum hybrid sudangrass to varying degrees. Compared with control group, high dosage of distiller's grain biochar and Lactobacillus plantarum thallus combined application treated Sorghum hybrid sudangrass with the lowest heavy metals content. The concentrations of Cd, Pb, and Zn decreased by 40.93%, 31.84%, and 40.25% in the aerial part, respectively, and decreased by 41.09%, 21.79%, and 29.62% in the root, respectively. The high dosage of distiller's grains biochar and the combination application of distiller's grains biochar and Lactobacillus plantarum thallus significantly increased the plant height and biomass of Sorghum hybrid sudangrass (P<0.05), and the overall promotion effect was better than other treatments.