Study of fusion peptide release for the spike protein of SARS-CoV-2.

The spike protein of SARS-CoV-2 can recognize the ACE2 membrane protein on the host cell and plays a key role in the membrane fusion process between the virus envelope and the host cell membrane. However, to date, the mechanism for the spike protein recognizing host cells and initiating membrane fusion remains unknown. In this study, based on the general assumption that all three S1/S2 junctions of the spike protein are cleaved, structures with different forms of S1 subunit stripping and S2' site cleavage were constructed. Then, the minimum requirement for the release of the fusion peptide was studied by all-atom structure-based MD simulations. The results from simulations showed that stripping an S1 subunit from the A-, B- or C-chain of the spike protein and cleaving the specific S2' site on the B-chain (C-chain or A-chain) may result in the release of the fusion peptide, suggesting that the requirement for the release of FP may be more relaxed than previously expected.

Estimating monthly surface ozone using multi-source satellite products in China based on Deep Forest model

Surface ozone (O3), a well-recognized air pollutant, exists in the atmosphere, which has a detrimental effect on public health and the ecological environment. It is reported that surface O3 has seen a significant increase in many cities from 2019 to 2021 (COVID-19 pandemic). In this study, we applied an innovative machine learning model (Deep Forest) coupled with satellites, the Troposphere Monitoring Instrument (TROPOMI) and the Ozone Monitoring Instrument (OMI), and meteorological datasets to estimate monthly surface O3 of 1 km spatial resolution across China during this pandemic period. Our model achieved an overall R2 of 0.974, 0.963, and root mean square error (RMSE) of 6.016 μg/m3, 7.214 μg/m3 on TROPOMI-based datasets and OMI-based datasets, respectively. Also, we found the higher ozone concentration regions were in Eastern China. Simultaneously, the surface O3 concentration was high in summer(average = 110.57 ± 15.01 μg/m3). And the ozone concentration in summer 2020 (average = 107.78 ± 13.90 μg/m3) declined unprecedently than in summer 2019 (average = 110.54 ± 16.58 μg/m3). Our results indicated that TROPOMI data could provide robust data support for surface ozone concentration estimation. Furthermore, this study could enhance our comprehension of the formation mechanisms of surface O3 in China and assist air environment management decision-making.

CRISPR-Cas12a Coupled with DNA Nanosheet-Amplified Fluorescence Anisotropy for Sensitive Detection of Biomolecules.

DNA nanosheets (DNSs) have been utilized effectively as a fluorescence anisotropy (FA) amplifier for biosensing. But, their sensitivity needs to be further improved. Herein, CRISPR-Cas12a with strong trans-cleavage activity was utilized to enhance the FA amplification ability of DNSs for the sensitive detection of miRNA-155 (miR-155) as a proof-of-principle target. In this method, the hybrid of the recognition probe of miR-155 (T1) and a blocker sequence (T2) was immobilized on the surface of magnetic beads (MBs). In the presence of miR-155, T2 was released by a strand displacement reaction, which activated the trans-cleavage activity of CRISPR-Cas12a. The single-stranded DNA (ssDNA) probe modified with a carboxytetramethylrhodamine (TAMRA) fluorophore was cleaved in large quantities and could not bind to the handle chain on DNSs, inducing a low FA value. In contrast, in the absence of miR-155, T2 could not be released and the trans-cleavage activity of CRISPR-Cas12a could not be activated. The TAMRA-modified ssDNA probe remained intact and was complementary to the handle chain on the DNSs, and a high FA value was obtained. Thus, miR-155 was detected through the obviously decreased FA value with a low limit of detection (LOD) of 40 pM. Impressively, the sensitivity of this method was greatly improved about 322 times by CRISPR-Cas12a, confirming the amazing signal amplification ability of CRISPR-Cas12a. At the same time, the SARS-CoV-2 nucleocapsid protein was detected by the strategy successfully, indicating that this method was general. Moreover, this method has been applied in the analysis of miR-155 in human serum and the lysates of cells, which provides a new avenue for the sensitive determination of biomarkers in biochemical research and disease diagnosis.

Reticulons promote formation of ER-derived double-membrane vesicles that facilitate SARS-CoV-2 replication.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent for the global COVID-19 pandemic, triggers the formation of endoplasmic reticulum (ER)-derived replication organelles, including double-membrane vesicles (DMVs), in the host cell to support viral replication. Here, we clarify how SARS-CoV-2 hijacks host factors to construct the DMVs. We show that the ER morphogenic proteins reticulon-3 (RTN3) and RTN4 help drive DMV formation, enabling viral replication, which leads to productive infection. Different SARS-CoV-2 variants, including the delta variant, use the RTN-dependent pathway to promote infection. Mechanistically, our results reveal that the membrane-embedded reticulon homology domain (RHD) of the RTNs is sufficient to functionally support viral replication and physically engage NSP3 and NSP4, two viral non-structural membrane proteins known to induce DMV formation. Our findings thus identify the ER morphogenic RTN3 and RTN4 membrane proteins as host factors that help promote the biogenesis of SARS-CoV-2-induced DMVs, which can act as viral replication platforms.

Metabolomic Profiling of Lungs from Mice Reveals the Variability of Metabolites in Pneumocystis Infection and the Metabolic Abnormalities in BAFF-R-Deficient Mice.

Purpose: The incidence of Pneumocystis pneumonia (PCP) in patients without human immunodeficiency virus (HIV) has been increasing. In this study, we aimed to investigate the metabolic changes in Pneumocystis infection and the metabolic abnormalities in B-cell-activating factor receptor (BAFF-R)-deficient mice with Pneumocystis infection. Methods: The important function of B cells during Pneumocystis infection is increasingly recognized. In this study, a Pneumocystis-infected mouse model was constructed in BAFF-R-/- mice and wild-type (WT) mice. Lungs of uninfected WT C57BL/6, WT Pneumocystis-infected, and BAFF-R-/- Pneumocystis-infected mice were used for metabolomic analyses to compare the metabolomic profiles among the groups, with the aim of exploring the metabolic influence of Pneumocystis infection and the influence of mature B-cell deficiency during infection. Results: The results indicated that many metabolites, mainly lipids and lipid-like molecules, were dysregulated in Pneumocystis-infected WT mice compared with uninfected WT C57BL/6 mice. The data also demonstrated significant changes in tryptophan metabolism, and the expression levels of key enzymes of tryptophan metabolism, such as indoleamine 2,3-dioxygenase 1 (IDO1), were significantly upregulated. In addition, B-cell development and function might be associated with lipid metabolism. We found a lower level of alitretinoin and the abnormalities of fatty acid metabolism in BAFF-R-/- Pneumocystis-infected mice. The mRNA levels of enzymes associated with fatty acid metabolism in the lung were upregulated in BAFF-R-/- Pneumocystis-infected mice and positively correlated with the level of IL17A, thus suggesting that the abnormalities of fatty acid metabolism may be associated with greater inflammatory cell infiltration in the lung tissue of BAFF-R-/- Pneumocystis-infected mice compared with the WT Pneumocystis-infected mice. Conclusion: Our data revealed the variability of metabolites in Pneumocystis-infected mice, suggesting that the metabolism plays a vital role in the immune response to Pneumocystis infection.

Blue LED light promoting the growth, accumulation of high-value isoflavonoids and astragalosides, antioxidant response, and biosynthesis gene expression in Astragalus membranaceus (Fisch.) Bunge hairy root cultures

The root of Astragalus membranaceus (Fisch.) Bunge is one of the most frequently used herbs in traditional Chinese medicine (TCM) formulae for fighting COVID-19 infections, due to the presence of isoflavonoids and astragalosides associated with antiviral and immune-enhancing activities. For the first time, the exposure of A. membranaceus hairy root cultures (AMHRCs) to different colors of LED lights i.e., red, green, blue, red/green/blue (1/1/1, RGB), and white, was conducted to promote the root growth and accumulation of isoflavonoids and astragalosides. LED light treatment regardless of colors was found beneficial for root growth, which might be a result of the formation of more root hairs upon light stimulation. Blue LED light was found most effective for enhancing phytochemical accumulation. Results showed that the productivity of root biomass in blue-light grown AMHRCs with an initial inoculum size of 0.6% for 55 days was 1.40-fold higher than that in dark (control), and yields of high-value isoflavonoids and astragalosides including calycosin, formononetin, astragaloside IV, and astragaloside I increased by 3.17-fold, 2.66-fold, 1.78-fold, and 1.52-fold relative to control, respectively. Moreover, the photooxidative stress together with transcriptional activation of biosynthesis genes might contribute to the enhanced accumulation of isoflavonoids and astragalosides in blue-light grown AMHRCs. Overall, this work offered a feasible approach for obtaining higher yields of root biomass and medicinally important compounds in AMHRCs via the simple supplementation of blue LED light, which made blue-light grown AMHRCs industrially attractive as plant factory in controlled growing systems. Graphical Supplementary Information The online version contains supplementary material available at 10.1007/s11240-023-02486-7. Key Message Blue LED light was found to simultaneously promote the root growth and accumulation of medicinally important compounds (calycosin, formononetin, astragaloside IV, and astragaloside I) in Astragalus membranaceus (Fisch.) Bunge hairy root cultures. Supplementary Information The online version contains supplementary material available at 10.1007/s11240-023-02486-7.

Uncertainty quantification of CO2 emissions from China's civil aviation industry to 2050.

To mitigate aviation's carbon emissions of the aviation industry, the following steps are vital: accurately quantifying the carbon emission path by considering uncertainty factors, including transportation demand in the post-COVID-19 pandemic period; identifying gaps between this path and emission reduction targets; and providing mitigation measures. Some mitigation measures that can be employed by China's civil aviation industry include the gradual realization of large-scale production of sustainable aviation fuels and transition to 100% sustainable and low-carbon sources of energy. This study identified the key driving factors of carbon emissions by using the Delphi Method and set scenarios that consider uncertainty, such as aviation development and emission reduction policies. A backpropagation neural network and Monte Carlo simulation were used to quantify the carbon emission path. The study results show that China's civil aviation industry can effectively help the country achieve its carbon peak and carbon neutrality goals. However, to achieve the net-zero carbon emissions goal of global aviation, China needs to reduce its emissions by approximately 82%-91% based on the optimal emission scenario. Thus, under the international net-zero target, China's civil aviation industry will face significant pressure to reduce its emissions. The use of sustainable aviation fuels is the best way to reduce aviation emissions by 2050. Moreover, in addition to the application of sustainable aviation fuel, it will be necessary to develop a new generation of aircraft introducing new materials and upgrading technology, implement additional carbon absorption measures, and make use of carbon trading markets to facilitate China's civil aviation industry's contribution to reduce climate change.

Blue LED light promoting the growth, accumulation of high-value isoflavonoids and astragalosides, antioxidant response, and biosynthesis gene expression in Astragalus membranaceus (Fisch.) Bunge hairy root cultures.

The root of Astragalus membranaceus (Fisch.) Bunge is one of the most frequently used herbs in traditional Chinese medicine (TCM) formulae for fighting COVID-19 infections, due to the presence of isoflavonoids and astragalosides associated with antiviral and immune-enhancing activities. For the first time, the exposure of A. membranaceus hairy root cultures (AMHRCs) to different colors of LED lights i.e., red, green, blue, red/green/blue (1/1/1, RGB), and white, was conducted to promote the root growth and accumulation of isoflavonoids and astragalosides. LED light treatment regardless of colors was found beneficial for root growth, which might be a result of the formation of more root hairs upon light stimulation. Blue LED light was found most effective for enhancing phytochemical accumulation. Results showed that the productivity of root biomass in blue-light grown AMHRCs with an initial inoculum size of 0.6% for 55 days was 1.40-fold higher than that in dark (control), and yields of high-value isoflavonoids and astragalosides including calycosin, formononetin, astragaloside IV, and astragaloside I increased by 3.17-fold, 2.66-fold, 1.78-fold, and 1.52-fold relative to control, respectively. Moreover, the photooxidative stress together with transcriptional activation of biosynthesis genes might contribute to the enhanced accumulation of isoflavonoids and astragalosides in blue-light grown AMHRCs. Overall, this work offered a feasible approach for obtaining higher yields of root biomass and medicinally important compounds in AMHRCs via the simple supplementation of blue LED light, which made blue-light grown AMHRCs industrially attractive as plant factory in controlled growing systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11240-023-02486-7.

Synthesis, molecular docking, and binding Gibbs free energy calculation of ß-nitrostyrene derivatives: Potential inhibitors of SARS-CoV-2 3CL protease.

The outbreak of novel coronavirus disease 2019 (COVID-19), caused by the novel coronavirus (SARS-CoV-2), has had a significant impact on human health and the economic development. SARS-CoV-2 3CL protease (3CLpro) is highly conserved and plays a key role in mediating the transcription of virus replication. It is an ideal target for the design and screening of anti-coronavirus drugs. In this work, seven ß-nitrostyrene derivatives were synthesized by Henry reaction and ß-dehydration reaction, and their inhibitory effects on SARS-CoV-2 3CL protease were identified by enzyme activity inhibition assay in vitro. Among them, 4-nitro-ß-nitrostyrene (compound a) showed the lowest IC50 values of 0.7297 µM. To investigate the key groups that determine the activity of ß-nitrostyrene derivatives and their interaction mode with the receptor, the molecular docking using the CDOCKER protocol in Discovery Studio 2016 was performed. The results showed that the hydrogen bonds between ß-NO2 and receptor GLY-143 and the π-π stacking between the aryl ring of the ligand and the imidazole ring of receptor HIS-41 significantly contributed to the ligand activity. Furthermore, the ligand-receptor absolute binding Gibbs free energies were calculated using the Binding Affinity Tool (BAT.py) to verify its correlation with the activity of ß-nitrostyrene 3CLpro inhibitors as a scoring function. The higher correlation(r2=0.6) indicates that the absolute binding Gibbs free energy based on molecular dynamics can be used to predict the activity of new ß-nitrostyrene 3CLpro inhibitors. These results provide valuable insights for the functional group-based design, structure optimization and the discovery of high accuracy activity prediction means of anti-COVID-19 lead compounds.

Key mutations in the spike protein of SARS-CoV-2 affecting neutralization resistance and viral internalization.

To control the ongoing COVID-19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been developed. However, the rapid mutations of SARS-CoV-2 spike (S) protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS-CoV-2, and then systematically assessed the susceptivity of these SARS-CoV-2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS-CoV-2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin-converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS-CoV-2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.

Impact of COVID-19 on the Comprehensive Resilience of Rural Areas - A Case Study of Jilin Province of China

It is of practical significance for rural revitalization to clarify the gap in resilience development among different rural areas and improve the ability to cope with external interference. Combined with the strategic policy of rural revitalization in China, the evaluation index system of rural comprehensive resilience was constructed from the five dimensions of productive resilience, ecological resilience, social resilience, institutional resilience, and economic resilience. The advantages and disadvantages of rural development are determined based on a quantitative evaluation of the comprehensive resilience of rural development. This could provide a reference for decision making in rural development. This study uses the rural statistical data of nine cities (prefectures) in Jilin Province in 2019 and 2020 as an example as well as the entropy weight method to evaluate the impact of COVID-19 on rural resilience development. The results showed that the pandemic situation has an obvious impact on rural economic resilience;rural areas with high ecological resilience have a strong ability to cope with the panidemic situation;and rural areas with excellent ecological environment resources have strong comprehensive resilience.

Factors affecting prolonged SARS-CoV-2 infection and development and validation of predictive nomograms.

Prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has received much attention since it is associated with mortality and is hypothesized as the cause of long COVID-19 and the emergence of a new variant of concerns. However, a prediction model for the accurate prediction of prolonged infection is still lacking. A total of 2938 confirmed patients with COVID-19 diagnosed by positive reverse transcriptase-polymerase chain reaction tests were recruited retrospectively. This study cohort was divided into a training set (70% of study patients; n = 2058) and a validation set (30% of study patients; n = 880). Univariate and multivariate logistic regression analyses were utilized to identify predictors for prolonged infection. Model 1 included only preadmission variables, whereas Model 2 also included after-admission variables. Nomograms based on variables of Model 1 and Model 2 were built for clinical use. The efficiency of nomograms was evaluated by using the area under the curve, calibration curves, and concordance indexes (C-index). Independent predictors of prolonged infection included in Model 1 were: age ≥75 years, chronic kidney disease, chronic lung disease, partially or fully vaccinated, and booster. Additional independent predictors in Model 2 were: treated with nirmatrelvir/ritonavir more than 5 days after diagnosis and glucocorticoid. The inclusion of after-admission variables in the model slightly improved the discriminatory power (C-index in the training cohort: 0.721 for Model 1 and 0.737 for Model 2; in the validation cohort: 0.699 for Model 1 and 0.719 for Model 2). In our study, we developed and validated predictive models based on readily available variables of preadmission and after-admission for predicting prolonged SARS-CoV-2 infection of patients with COVID-19.

Tracking of Mutational Signature of SARS-CoV-2 Omicron on Distinct Continents and Little Difference was Found.

The Omicron variant is currently ravaging the world, raising serious concern globally. Monitoring genomic variations and determining their influence on biological features are critical for tracing its ongoing transmission and facilitating effective measures. Based on large-scale sequences from different continents, this study found that: (i) The genetic diversity of Omicron is much lower than that of the Delta variant. Still, eight deletions (Del 1-8) and 1 insertion, as well as 130 SNPs, were detected on the Omicron genomes, with two deletions (Del 3 and 4) and 38 SNPs commonly detected on all continents and exhibiting high-occurring frequencies. (ii) Four groups of tightly linked SNPs (linkage I-IV) were detected, among which linkage I, containing 38 SNPs, with 6 located in the RBD, increased its occurring frequency remarkably over time. (iii) The third codons of the Omicron shouldered the most mutation pressures, while the second codons presented the least flexibility. (iv) Four major mutants with amino acid substitutions in the RBD were detected, and further structural analysis suggested that the substitutions did not alter the viral receptor binding ability greatly. It was inferred that though the Omicron genome harbored great changes in antigenicity and remarkable ability to evade immunity, it was immune-pressure selected. This study tracked mutational signatures of Omicron variant and the potential biological significance of the SNPs, and the linkages await further functional verification.

A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

Eugenol Alleviates TGEV-Induced Intestinal Injury via Suppressing ROS/NLRP3/GSDMD-Dependent Pyroptosis.

Transmissible gastroenteritis virus (TGEV), a coronavirus, is one of the main causative agents of diarrhea in piglets and significantly impacts the global swine industry. Pyroptosis is involved in the pathogenesis of coronavirus, but its role in TGEV-induced intestinal injury has yet to be fully elucidated. Eugenol, an essential plant oil, plays a vital role in antiviral innate immune responses. We demonstrate the preventive effect of eugenol on TGEV infection. Eugenol alleviates TGEV-induced intestinal epithelial cell pyroptosis and reduces intestinal injury in TGEV-infected piglets. Mechanistically, eugenol reduces the activation of NLRP3 inflammasome, thereby inhibiting TGEV-induced intestinal epithelial cell pyroptosis. In addition, eugenol scavenges TGEV-induced reactive oxygen species (ROS) increase, which in turn prevents TGEV-induced NLRP3 inflammasome activation and pyroptosis. Overall, eugenol protects the intestine by reducing TGEV-induced pyroptosis through inhibition of NLRP3 inflammasome activation, which may be mediated through intracellular ROS levels. These findings propose that eugenol may be an effective strategy to prevent TGEV infection.

A practical scoring model to predict the occurrence of critical illness in hospitalized patients with SARS-CoV-2 omicron infection.

Background: The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged repeatedly, especially the Omicron strain which is extremely infectious, so early identification of patients who may develop critical illness will aid in delivering proper treatment and optimizing use of resources. We aimed to develop and validate a practical scoring model at hospital admission for predicting which patients with Omicron infection will develop critical illness. Methods: A total of 2,459 patients with Omicron infection were enrolled in this retrospective study. Univariate and multivariate logistic regression analysis were performed to evaluate predictors associated with critical illness. Moreover, the area under the receiver operating characteristic curve (AUROC), continuous net reclassification improvement, and integrated discrimination index were assessed. Results: The derivation cohort included 1721 patients and the validation cohort included 738 patients. A total of 98 patients developed critical illness. Thirteen variables were independent predictive factors and were included in the risk score: age > 65, C-reactive protein > 10 mg/L, lactate dehydrogenase > 250 U/L, lymphocyte < 0.8*10^9/L, white blood cell > 10*10^9/L, Oxygen saturation < 90%, malignancy, chronic kidney disease, chronic cardiac disease, chronic obstructive pulmonary disease, diabetes, cerebrovascular disease, and non-vaccination. AUROC in the derivation cohort and validation cohort were 0.926 (95% CI, 0.903-0.948) and 0.907 (95% CI, 0.860-0.955), respectively. Moreover, the critical illness risk scoring model had the highest AUROC compared with CURB-65, sequential organ failure assessment (SOFA) and 4C mortality scores, and always obtained more net benefit. Conclusion: The risk scoring model based on the characteristics of patients at the time of admission to the hospital may help medical practitioners to identify critically ill patients and take prompt measures.

Blue LED light promoting the growth, accumulation of high-value isoflavonoids and astragalosides, antioxidant response, and biosynthesis gene expression in Astragalus membranaceus (Fisch.) Bunge hairy root cultures (preprint)

The root of Astragalus membranaceus (Fisch.) Bunge is one of the most frequently used herbs in traditional Chinese medicine (TCM) formulae for fighting COVID-19 infections, due to the presence of isoflavonoids and astragalosides associated with antiviral and immune-enhancing activities. For the first time, the exposure of A. membranaceus hairy root cultures (AMHRCs) to different colors of LED lights i.e., red, green, blue, red/green/blue (1/1/1, RGB), and white, was conducted to promote the root growth and accumulation of isoflavonoids and astragalosides. LED light treatment regardless of colors was found beneficial for root growth, which might be a result of the formation of more root hairs upon light stimulation. Blue LED light was found most effective for enhancing phytochemical accumulation. Results showed that the productivity of root biomass in blue-light grown AMHRCs with an initial inoculum size of 0.6% for 55 days was 1.40-fold higher than that in dark (control), and yields of high-value isoflavonoids and astragalosides including calycosin, formononetin, astragaloside IV, and astragaloside I increased by 3.17-fold, 2.66-fold, 1.78-fold, and 1.52-fold relative to control, respectively. Moreover, the photooxidative stress together with transcriptional activation of biosynthesis genes might contribute to the enhanced accumulation of isoflavonoids and astragalosides in blue-light grown AMHRCs. Overall, this work offered a feasible approach for obtaining higher yields of root biomass and medicinally important compounds in AMHRCs via the simple supplementation of blue LED light, which made blue-light grown AMHRCs industrially attractive as plant factory in controlled growing systems.

Risk factors for pulmonary embolism in patients with COVID-19: a systemic review and meta-analysis.

PURPOSE: To detect the risk factors for pulmonary embolism (PE) in patients with COVID-19. METHODS: Studies were searched for in PubMed, Cochrane Library, Web of Science, and EMBASE. Two authors independently screened articles and extracted data. The data were pooled by meta-analysis and three subgroup analyses were performed. RESULTS: Of the 2210 articles identified, 27 studies were included. Pooled analysis suggested that males (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.26-1.75, P = 0.000), obesity (OR 1.37, 95% CI 1.03-1.82, P = 0.033), mechanical ventilation (OR 3.34, 95% CI 1.90-5.86, P = 0.000), severe parenchymal abnormalities (OR 1.92, 95% CI 1.43-2.58, P = 0.000), ICU admission (OR 2.44, 95% CI 1.48-4.03, P = 0.000), and elevated D-dimer and white blood cell values (at two time points: hospital admission or closest to computed tomography pulmonary angiography) (P = 0.000) correlated with a risk for PE occurrence in COVID-19 patients. However, age and common comorbidities had no association with PE occurrence. Computed tomography pulmonary angiography, unclear-ratio/low-ratio, and hospitalization subgroups had consistent risk factors with all studies; however, other subgroups had fewer risk factors for PE. CONCLUSIONS: Risk factors for PE in COVID-19 were different from the classic risk factors for PE and are likely to differ in diverse study populations.

Eugenol Attenuates Transmissible Gastroenteritis Virus-Induced Oxidative Stress and Apoptosis Via ROS-NRF2-ARE Signaling.

Transmissible gastroenteritis virus (TGEV), a coronavirus that causes severe diarrhea due to oxidative stress in the piglet intestine, is a major cause of economic loss in the livestock industry. However, limited interventions have been shown to be effective in the treatment of TGEV. Here, we demonstrate the therapeutic activity of eugenol in TGEV-induced intestinal oxidative stress and apoptosis. Our data show that eugenol supplementation protects intestine and IPEC-J2 cells from TGEV-induced damage. Mechanistically, eugenol reduces TGEV-induced oxidative stress in intestinal epithelial cells by reducing reactive oxygen species levels. Interestingly, eugenol also inhibits TGEV-induced intestinal cell apoptosis in vitro and in vivo. In conclusion, our data suggest that eugenol prevents TGEV-induced intestinal oxidative stress by reducing ROS-mediated damage to antioxidant signaling pathways. Therefore, eugenol may be a promising therapeutic strategy for TGEV infection.

Is replacing red meat with other protein sources associated with lower risks of coronary heart disease and all-cause mortality? A meta-analysis of prospective studies.

CONTEXT: A high amount of red meat consumption has been associated with higher risks of coronary heart disease (CHD) and all-cause mortality in a single food-exposure model. However, this model may overlook the potentially differential influence of red meat on these outcomes depending on the foods replaced by red meat. OBJECTIVE: A PRISMA-compliant meta-analysis of prospective observational studies was performed to quantify the risks of CHD and all-cause mortality associated with the replacement of total, unprocessed, or processed red meat with fish/seafood, poultry, dairy, eggs, nuts, and legumes. DATA SOURCES: The PubMed and Web of Science databases were searched to identify relevant articles published in any language from database inception to October 30, 2021. DATA EXTRACTION: The prospective observational studies were considered relevant if they reported relative risks (RRs) and 95%CIs for the associations of interest. DATA ANALYSIS: Thirteen articles were included. A random-effects model was used to estimate the summary RRs and 95%CIs for the associations of interest. Replacing total red meat with poultry (RR, 0.88, 95%CI, 0.82-0.96; I2 = 0%), dairy (RR, 0.90, 95%CI, 0.88-0.92; I2 = 0%), eggs (RR, 0.86, 95%CI, 0.79-0.94; I2 = 7.1%), nuts (RR, 0.84, 95%CI, 0.74-0.95; I2 = 66.8%), or legumes (RR, 0.84, 95%CI, 0.74-0.95; I2 = 7.3%) was associated with a lower risk of CHD, whereas substituting fish/seafood (RR, 0.91, 95%CI, 0.79-1.04; I2 = 69.5%) for total red meat was not associated with the risk of CHD. The replacement of total red meat with fish/seafood (RR, 0.92, 95%CI, 0.89-0.96; I2 = 86.9%), poultry (RR, 0.92, 95%CI, 0.90-0.95; I2 = 61.6%), eggs (RR, 0.91, 95%CI, 0.87-0.95; I2 = 33.8%), or nuts (RR, 0.92, 95%CI, 0.87-0.97; I2 = 81.9%) was associated with a lower risk of all-cause mortality, whereas the substitution of dairy (RR, 0.97, 95%CI, 0.93-1.01; I2 = 33.9%) or legumes (RR, 0.97, 95%CI, 0.93-1.01; I2 = 53.5%) for total red meat was not associated with the risk of all-cause mortality. Lower risks of CHD and all-cause mortality were more consistently observed for processed red meat replacements than for unprocessed red meat replacements. The results did not materially change when the analyses of total, processed, and unprocessed red meat were restricted to the studies that used a uniform substitution amount per unit of 1 serving/d. CONCLUSION: Keeping red meat, particularly processed red meat, consumption to a minimum along with increasing healthier alternative protein sources to replace red meat in the diet may contribute to the prevention of CHD and premature death. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021259446.