Hypericin Inhibit Alpha-Coronavirus Replication by Targeting 3CL Protease

The porcine epidemic diarrhea virus (PEDV) is an Alphacoronavirus (α-CoV) that causes high mortality in infected piglets, resulting in serious economic losses in the farming industry. Hypericin is a dianthrone compound that has been shown as an antiviral activity on several viruses. Here, we first evaluated the antiviral effect of hypericin in PEDV and found the viral replication and egression were significantly reduced with hypericin post-treatment. As hypericin has been shown in SARS-CoV-2 that it is bound to viral 3CLpro, we thus established a molecular docking between hypericin and PEDV 3CLpro using different software and found hypericin bound to 3CLpro through two pockets. These binding pockets were further verified by another docking between hypericin and PEDV 3CLpro pocket mutants, and the fluorescence resonance energy transfer (FRET) assay confirmed that hypericin inhibits the PEDV 3CLpro activity. Moreover, the alignments of α-CoV 3CLpro sequences or crystal structure revealed that the pockets mediating hypericin and PEDV 3CLpro binding were highly conserved, especially in transmissible gastroenteritis virus (TGEV). We then validated the anti-TGEV effect of hypericin through viral replication and egression. Overall, our results push forward that hypericin was for the first time shown to have an inhibitory effect on PEDV and TGEV by targeting 3CLpro, and it deserves further attention as not only a pan-anti-α-CoV compound but potentially also as a compound of other coronaviral infections

Microbial responses to inorganic nutrient amendment overridden by warming: Consequences on soil carbon stability.

Eutrophication and climate warming, induced by anthropogenic activities, are simultaneously occurring worldwide and jointly affecting soil carbon stability. Therefore, it is of great interest to examine whether and how they interactively affect soil microbial community, a major soil carbon driver. Here, we showed that climate warming, simulated by southward transferring Mollisol soil in agricultural ecosystems from the cold temperate climate zone (N) to warm temperate climate (C) and subtropical climate zone (S), decreased soil organic matter (SOM) by 6%-12%. In contrast, amendment with nitrogen, phosphorus and potassium enhanced plant biomass by 97% and SOM by 6% at the N site, thus stimulating copiotrophic taxa but reducing oligotrophic taxa in relative abundance. However, microbial responses to nutrient amendment were overridden by soil transfer in that nutrient amendment had little effect at the C site but increased recalcitrant carbon-degrading fungal Agaricomycetes and Microbotryomycetes taxa derived from Basidiomycota by 4-17 folds and recalcitrant carbon-degrading genes by 23%-40% at the S site, implying a possible priming effect. Consequently, SOM at the S site was not increased by nutrient amendment despite increased plant biomass by 108%. Collectively, we demonstrate that soil transfer to warmer regions overrides microbial responses to nutrient amendment and weakens soil carbon sequestration

Association between ambient air pollution and hospital admissions, length of hospital stay and hospital cost for patients with cardiovascular diseases and comorbid diabetes mellitus: Base on 1,969,755 cases in Beijing, China, 2014–2019

Background: Evidence on the effects of the air pollutants on the hospital admissions, hospital cost and length of stay (LOS) among patients with comorbidities remains limited in China, particularly for patients with cardiovascular diseases and comorbid diabetes mellitus (CVD-DM). Methods: We collected daily data on CVD-DM patients from 242 hospitals in Beijing between 2014 and 2019. Generalized additive model was employed to quantify the associations between admissions, LOS, and hospital cost for CVD-DM patients and air pollutants. We further evaluated the attributable risk posed by air pollutants to CVD-DM patients, using both Chinese and WHO air quality guidelines as reference. Results: Per 10 ug/m3 increase of particles with an aerodynamic diameter \u3c 2.5 μm (PM2.5), particles with an aerodynamic diameter \u3c 10 μm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbonic oxide (CO) and ozone (O3) corresponded to a 0.64% (95% CI: 0.57 to 0.71), 0.52% (95% CI: 0.46 to 0.57), 0.93% (95% CI: 0.67 to 1.20), 0.98% (95% CI: 0.81 to 1.16), 1.66% (95% CI: 1.18 to 2.14) and 0.53% (95% CI: 0.45 to 0.61) increment for CVD-DM patients’ admissions. Among the six pollutants, particulate pollutants (PM2.5 and PM10) in most lag days exhibited adverse effects on LOS and hospital cost. For every 10 ug/m3 increase in PM2.5 and PM10, the absolute increase with LOS will increase 62.08 days (95% CI: 28.93 to 95.23) and 51.77 days (95% CI:22.88 to 80.66), respectively. The absolute increase with hospital cost will increase 105.04 Chinese Yuan (CNY) (95% CI: 49.27 to 160.81) and 81.76 CNY (95% CI: 42.01 to 121.51) in PM2.5 and PM10, respectively. Given WHO 2021 air quality guideline as the reference, PM2.5 had the maximum attributable fraction of 3.34% (95% CI: 2.94% to 3.75%), corresponding to an avoidable of 65,845 (95% CI: 57,953 to 73,812) patients with CVD-DM. Conclusion: PM2.5 and PM10 are positively associated with hospital admissions, hospital cost and LOS for patients with CVD-DM. Policy changes to reduce air pollutants exposure may reduce CVD-DM admissions and substantial savings in health care spending and LOS

Acute effect of particulate matter pollution on hospital admissions for cause-specific respiratory diseases among patients with and without type 2 diabetes in Beijing, China, from 2014 to 2020

BACKGROUND: Scientific studies have identified various adverse effects of particulate matter (PM) on respiratory disease (RD) and type 2 diabetes (T2D). However, whether short-term exposure to PM triggers the onset of RD with T2D, compared with RD without T2D, has not been elucidated. METHODS: A two-stage time-series study was conducted to evaluate the acute adverse effects of PM on admission for RD and for RD with and without T2D in Beijing, China, from 2014 to 2020. District-specific effects of PM and PM were estimated using the over-dispersed Poisson generalized addictive model after adjusting for weather conditions, day of the week, and long-term and seasonal trends. Meta-analyses were applied to pool the overall effects on overall and cause-specific RD, while the exposure-response (E-R) curves were evaluated using a cubic regression spline. RESULTS: A total of 1550,154 admission records for RD were retrieved during the study period. Meta-analysis suggested that per interquartile range upticks in the concentration of PM corresponded to 1.91% (95% CI: 1.33-2.49%), 2.16% (95% CI: 1.08-3.25%), and 1.92% (95% CI: 1.46-2.39%) increments in admission for RD, RD with T2D, and RD without T2D, respectively, at lag 0-8 days, lag 8 days, and lag 8 days. The effect size of PM was statistically significantly higher in the T2D group than in the group without T2D (z = 3.98, P \u3c 0.01). The effect sizes of PM were 3.86% (95% CI: 2.48-5.27%), 3.73% (95% CI: 1.72-5.79%), and 3.92% (95% CI: 2.65-5.21%), respectively, at lag 0-13 days, lag 13 days, and lag 13 days, respectively, and no statistically significant difference was observed between T2D groups (z = 0.24, P = 0.81). Significant difference was not observed between T2D groups for the associations of PM and different RD and could be found between three groups for effects of PM on RD without T2D. The E-R curves varied by sex, age and T2D condition subgroups for the associations between PM and daily RD admissions. CONCLUSIONS: Short-term PM exposure was associated with increased RD admission with and without T2D, and the effect size of PM was higher in patients with T2D than those without T2D