The mechanism of Qingwen Gupi decoction on pulmonary fibrosis based on metabolomics and intestinal flora.

AIMS: To evaluate the effects of the Qingwen Gupi decoction (QGT) in a rat model of bleomycin-induced pulmonary fibrosis (PF), and explore the underlying mechanisms by integrating UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing of gut microbiota. METHODS AND RESULTS: The animals were randomly divided into the control, PF model, pirfenidone-treated, and low-, medium-, and high-dose QGT groups. The lung tissues were examined and the expression of TGF-ß, SMAD-3, and SMAD-7 mRNAs in the lung tissues were analyzed. Metabolomic profiles were analyzed by UPLC-QTOF/MS, and the intestinal flora were examined by prokaryotic 16 rDNA sequencing. Pathological examination and biochemical indices revealed that QGT treatment improved the symptoms of PF by varying degrees. Furthermore, QGT significantly downregulated TGF-ß1 and Smad-3 mRNAs and increased the expression levels of Smad-7. QGT-L in particular increased the levels of 18 key metabolic biomarkers that were associated with nine gut microbial species and may exert antifibrosis effects through arachidonic acid metabolism, glycerophospholipid metabolism, and phenylalanine metabolism. CONCLUSIONS: QGT alleviated PF in a rat model through its anti-inflammatory, antioxidant, and anti-fibrotic effects, and by reversing bleomycin-induced gut dysbiosis.This study lays the foundation for further research on the pathological mechanisms of PF and the development of new drug candidates.

Progress in the distribution characteristics and risks of bioaerosols from anthropogenic sources

In recent years, the global outbreak of COVID-19 has aroused public attention to the potential risks of bioaerosols and the studies about the potential health hazards of bioaerosols from anthropogenic sources have been increasing. We introduced the research status of four main anthropogenic bioaerosols in recent years, compared the distribution and composition characteristics of bioaerosols from different anthropogenic sources, and analyzed the main factors affecting the characteristics and potential risks of bioaerosols. The average concentration of bioaerosol is high in animal farms, moderate in wastewater treatment plants and landfills, and low in hospitals. The microbial composition of bioaerosols at different sites is closely associated with the bioaerosol source and affected by the environmental conditions. Furthermore, this work prospected the main research directions of anthropogenic bioaerosols in the future, aiming to lay a foundation for the establishment of bioaerosol control standards and the development of control technology.

SARS-CoV-2 Variants Associated with Vaccine Breakthrough in the Delaware Valley through Summer 2021.

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25-3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. IMPORTANCE SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.

The prognostic value of the Barthel Index for mortality in patients with COVID-19: A cross-sectional study.

Objective: This study aimed to analyze the association between the activity of daily living (ADL), coronavirus disease (COVID-19), and the value of the Barthel Index in predicting the prognosis of patients. Methods: This study included 398 patients with COVID-19, whose ADL at admission to hospital were assessed with the Barthel Index. The relationship between the index and the mortality risk of the patients was analyzed. Several regression models and a decision tree were established to evaluate the prognostic value of the index in COVID-19 patients. Results: The Barthel Index scores of deceased patients were significantly lower than that of discharged patients (median: 65 vs. 90, P < 0.001), and its decrease indicated an increased risk of mortality in patients (P < 0.001). After adjusting models for age, gender, temperature, pulse, respiratory rate, mean arterial pressure, oxygen saturation, etc., the Barthel Index could still independently predict prognosis (OR = 0.809; 95% CI: 0.750-0.872). The decision tree showed that patients with a Barthel Index of below 70 had a higher mortality rate (33.3-40.0%), while those above 90 were usually discharged (mortality: 2.7-7.2%). Conclusion: The Barthel Index is of prognostic value for mortality in COVID-19 patients. According to their Barthel Index, COVID-19 patients can be divided into emergency, observation, and normal groups (0-70; 70-90; 90-100), with different treatment strategies.

Anti-inflammatory or anti-SARS-CoV-2 ingredients in Huashi Baidu Decoction and their corresponding targets: Target screening and molecular docking study.

Coronavirus disease 2019 (COVID-19) is a rapidly emerging infectious disease caused by SARS-CoV-2. Inflammatory factors may play essential roles in COVID-19 progression. Huashi Baidu Decoction (HSBD) is a traditional Chinese medicine (TCM) formula that can expel cold, dispel dampness, and reduce inflammation. HSBD has been widely used for the treatment of COVID-19. However, the active ingredients and potential targets for HSBD to exert anti-inflammatory or anti-SARS-CoV-2 effects remain unclear. In this paper, the active ingredients with anti-inflammatory or anti-viral effects in HSBD and their potential targets were screened using the Discovery Studio 2020 software. By overlapping the targets of HSBD and COVID-19, 8 common targets (FYN, SFTPD, P53, RBP4, IL1RN, TTR, SRPK1, and AKT1) were identified. We determined 2 key targets (P53 and AKT1) by network pharmacology. The main active ingredients in HSBD were evaluated using the key targets as receptor proteins for molecular docking. The results suggested that the best active ingredients Kaempferol2 and Kaempferol3 have the potential as supplements for the treatment of COVID-19.

The prognostic value of the Barthel Index for mortality in patients with COVID-19: A cross-sectional study

Objective This study aimed to analyze the association between the activity of daily living (ADL), coronavirus disease (COVID-19), and the value of the Barthel Index in predicting the prognosis of patients. Methods This study included 398 patients with COVID-19, whose ADL at admission to hospital were assessed with the Barthel Index. The relationship between the index and the mortality risk of the patients was analyzed. Several regression models and a decision tree were established to evaluate the prognostic value of the index in COVID-19 patients. Results The Barthel Index scores of deceased patients were significantly lower than that of discharged patients (median: 65 vs. 90, P < 0.001), and its decrease indicated an increased risk of mortality in patients (P < 0.001). After adjusting models for age, gender, temperature, pulse, respiratory rate, mean arterial pressure, oxygen saturation, etc., the Barthel Index could still independently predict prognosis (OR = 0.809;95% CI: 0.750–0.872). The decision tree showed that patients with a Barthel Index of below 70 had a higher mortality rate (33.3–40.0%), while those above 90 were usually discharged (mortality: 2.7–7.2%). Conclusion The Barthel Index is of prognostic value for mortality in COVID-19 patients. According to their Barthel Index, COVID-19 patients can be divided into emergency, observation, and normal groups (0–70;70–90;90–100), with different treatment strategies.

Computer-aided drug design combined network pharmacology to explore anti-SARS-CoV-2 or anti-inflammatory targets and mechanisms of Qingfei Paidu Decoction for COVID-19.

Introduction: Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by SARS-CoV-2. Severe cases of COVID-19 are characterized by an intense inflammatory process that may ultimately lead to organ failure and patient death. Qingfei Paidu Decoction (QFPD), a traditional Chines e medicine (TCM) formula, is widely used in China as anti-SARS-CoV-2 and anti-inflammatory. However, the potential targets and mechanisms for QFPD to exert anti-SARS-CoV-2 or anti-inflammatory effects remain unclear. Methods: In this study, Computer-Aided Drug Design was performed to identify the antiviral or anti-inflammatory components in QFPD and their targets using Discovery Studio 2020 software. We then investigated the mechanisms associated with QFPD for treating COVID-19 with the help of multiple network pharmacology approaches. Results and discussion: By overlapping the targets of QFPD and COVID-19, we discovered 8 common targets (RBP4, IL1RN, TTR, FYN, SFTPD, TP53, SRPK1, and AKT1) of 62 active components in QFPD. These may represent potential targets for QFPD to exert anti-SARS-CoV-2 or anti-inflammatory effects. The result showed that QFPD might have therapeutic effects on COVID-19 by regulating viral infection, immune and inflammation-related pathways. Our work will promote the development of new drugs for COVID-19.

Microfluidic bioprinting of tough hydrogel-based vascular conduits for functional blood vessels.

Three-dimensional (3D) bioprinting of vascular tissues that are mechanically and functionally comparable to their native counterparts is an unmet challenge. Here, we developed a tough double-network hydrogel (bio)ink for microfluidic (bio)printing of mono- and dual-layered hollow conduits to recreate vein- and artery-like tissues, respectively. The tough hydrogel consisted of energy-dissipative ionically cross-linked alginate and elastic enzyme-cross-linked gelatin. The 3D bioprinted venous and arterial conduits exhibited key functionalities of respective vessels including relevant mechanical properties, perfusability, barrier performance, expressions of specific markers, and susceptibility to severe acute respiratory syndrome coronavirus 2 pseudo-viral infection. Notably, the arterial conduits revealed physiological vasoconstriction and vasodilatation responses. We further explored the feasibility of these conduits for vascular anastomosis. Together, our study presents biofabrication of mechanically and functionally relevant vascular conduits, showcasing their potentials as vascular models for disease studies in vitro and as grafts for vascular surgeries in vivo, possibly serving broad biomedical applications in the future.

High attack rate in a Tong Lau house outbreak of COVID-19 with subdivided units in Hong Kong.

Poor housing conditions are known to be associated with infectious diseases such as high Coronavirus disease 2019 (COVID-19) incidences. Transmission causes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in poor housing conditions can be complex. An understanding of the exact mechanism of transmission can help to pinpoint contributing environmental issues. Here, we investigated a Hong Kong COVID-19 outbreak in early 2021 in four traditional Tong Lau houses with subdivided units. There are more than 80 subdivided units of less than 20 m2 floor area each on average. With a total of 34 confirmed COVID-19 cases, the outbreak had an attack rate of 25.4%, being one of the highest attack rates observed in Hong Kong, and ranked among the highest attack rates in reported outbreaks internationally. Tracer gas leakage and decay measurements were performed in the drainage system and in the subdivided units to determine the transport of infectious aerosols by the owner-modified sophisticated wastewater drainage pipe networks and the poor ventilation conditions in some subdivided units. The results show that the outbreak was probably due to multiple transmission routes, i.e. by the drainage pipe spread of stack aerosols, which is enhanced by poor ventilation in the subdivided units.

3-Dimensional Printed Alternative to the Standard Synthetic Flocked Nasopharyngeal Swabs Used for Coronavirus Disease 2019 Testing.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be detected in respiratory samples by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or other molecular methods. Accessibility of diagnostic testing for COVID-19 has been limited by intermittent shortages of supplies required for testing, including flocked nasopharyngeal (FLNP) swabs. METHODS: We developed a 3-dimensional printed nasopharyngeal (3DP) swab as a replacement of the FLNP swab. The performance of 3DP and FLNP swabs were compared in a clinical trial of symptomatic patients at 3 clinical sites (n = 291) using 3 SARS-CoV-2 emergency use authorization tests: a modified version of the Centers for Disease Control and Prevention (CDC) RT-PCR Diagnostic Panel and 2 commercial automated formats, Roche Cobas and NeuMoDx. RESULTS: The cycle threshold-C(t)-values from the gene targets and the RNase P gene control in the CDC assay showed no significant differences between swabs for both gene targets (P = .152 and P = .092), with the RNase P target performing significantly better in the 3DP swabs (P < .001). The C(t) values showed no significant differences between swabs for both viral gene targets in the Roche cobas assay (P = .05 and P = .05) as well as the NeuMoDx assay (P = .401 and P = .484). The overall clinical correlation of COVID-19 diagnosis between all methods was 95.88% (Kappa 0.901). CONCLUSIONS: The 3DP swabs were equivalent to standard FLNP in 3 testing platforms for SARS-CoV-2. Given the need for widespread testing, 3DP swabs printed onsite are an alternate to FLNP that can rapidly scale in response to acute needs when supply chain disruptions affect availability of collection kits.

Kaempferol alleviates human endothelial cell injury through circNOL12/miR-6873-3p/FRS2 axis.

BACKGROUND: Atherosclerosis, inflammatory disease, is a major reason for cardiovascular diseases and stroke. Kaempferol (Kae) has been well-documented to have pharmacological activities in the previous studies. However, the detailed mechanisms by which Kae regulates inflammation, oxidative stress, and apoptosis in Human Umbilical Vein Endothelial Cells (HUVECs) remain unknown. METHODS AND RESULTS: The real-time quantitative polymerase chain reaction (RT-qPCR) was used to measure expression levels of circNOL12, nucleolar protein 12 (NOL12), miR-6873-3p, and Fibroblast growth factor receptor substrate 2 (FRS2) in HUVECs treated with either oxidized low-density lipoprotein (ox-LDL) alone or in combination with Kae. The cells viability was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) assay. The inflammation and oxidative stress were assessed by checking inflammatory factors, Reactive Oxygen Species (ROS), Superoxide Dismutase (SOD), and Malondialdehyde (MDA) levels in ox-LDL-induced HUVECs. The apoptotic cells were quantified by flow cytometry assay. The western blot assay was used for measuring protein expression. The interaction relationship between miR-6873-3p and circNOL12 or FRS2 was analyzed by dual-luciferase reporter and RNA pull-down assays. Treatment with Kae could inhibit ox-LDL-induced the upregulation of circNOL12 in HUVECs. Importantly, Kae weakened ox-LDL-induced inflammation, oxidative stress, and apoptosis in HUVECs, which was abolished by overexpression of circNOL12. What's more, miR-6873-3p was a target of circNOL12 in HUVECs, and the upregulation of miR-6873-3p overturned circNOL12 overexpression-induced effects on HUVECs treated with ox-LDL and Kae. FRS2 was negatively regulated by miR-6873-3p in HUVECs. CONCLUSION: Kae alleviated ox-LDL-induced inflammation, oxidative stress, and apoptosis in HUVECs by regulating circNOL12/miR-6873-3p/FRS2 axis.

Screening out anti-inflammatory or anti-viral targets in Xuanfei Baidu Tang through a new technique of reverse finding target.

Traditional Chinese herbal compound prescription in Xuanfei Baidu Tang (XBT) has obvious effects in the treatment of COVID-19. However, its effective compounds and targets for the treatment of COVID-19 remain unclear. Computer-Aided Drug Design is used to virtually screen out the anti-inflammatory or anti-viral compounds in XBT, and predict the potential targets by Discovery Studio 2020. Then, we searched for COVID-19 targets using Genecards databases and Protein Data Bank (PDB) databases and compared them to identify targets that were common to both. Finally, the target we screened out is: TP53 (Tumor Protein P53). This article also shows that XBT in the treatment of COVID-19 works in a multi-link and overall synergistic manner. Our results will help to design the new drugs for COVID-19.

Aerosol transmission of SARS-CoV-2 due to the chimney effect in two high-rise housing drainage stacks.

Stack aerosols are generated within vertical building drainage stacks during the discharge of wastewater containing feces and exhaled mucus from toilets and washbasins. Fifteen stack aerosol-related outbreaks of coronavirus disease 2019 (COVID-19) in high-rise buildings have been observed in Hong Kong and Guangzhou. Currently, we investigated two such outbreaks of COVID-19 in Hong Kong, identified the probable role of chimney effect-induced airflow in a building drainage system in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We injected tracer gas (SF6) into the drainage stacks via the water closet of the index case and monitored tracer gas concentrations in the bathrooms and along the facades of infected and non-infected flats and in roof vents. The air temperature, humidity, and pressure in vertical stacks were also monitored. The measured tracer gas distribution agreed with the observed distribution of the infected cases. Phylogenetic analysis of the SARS-CoV-2 genome sequences demonstrated clonal spread from a point source in cases along the same vertical column. The stack air pressure and temperature distributions suggested that stack aerosols can spread to indoors through pipe leaks which provide direct evidence for the long-range aerosol transmission of SARS-CoV-2 through drainage pipes via the chimney effect.

Diagnostic value of the serum levels of high-sensitivity c-reactive protein,wbc, lymghocyte and neutrophil counts in COVID-19

Objective To investigate the diagnostic value of the count of serum hypersensitive C-reactive protein (serum hs-CRP) and white blood cell (WBC), lymphocyte (LY) and neutrophil (NT) in coronavirus disease 2019 (COVID-19). Methods Seventy-two patients of pulmonary infection from June to August 2020 were divided into the experimental group (36 cases) and bacterial group (36 cases) according to the infection pathogen, and 30 healthy people were set as the control group. The serum hs-CRP,WBC,LY and NT were measured and compared among three groups, and the sensitivity, specificity and receiver operating characteristic (ROC) curves of four indexes were calculated and plotted. Results The differences of the serum hs-CRP,WBC,LY and NT among three groups were statistically significant (P<0.01). When the combination of four indicators was used to diagnose the COVID-19, the area under the ROC curve of the combination were 0.994, and their sensitivity (100%) and specificity (94.4%) were the highest. Conclusions The serum hs-CRP,WBC,LY and NT have certain diagnostic value in COVID-19. Moreover, the sensitivity and specificity of the combination of four indicators are higher.

Clinical Performance of the Point-of-Care cobas Liat for Detection of SARS-CoV-2 in 20 Minutes: a Multicenter Study.

Highly accurate testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the point of care (POC) is an unmet diagnostic need in emergency care and time-sensitive outpatient care settings. Reverse transcription-PCR (RT-PCR) technology is the gold standard for SARS-CoV-2 diagnostics. We performed a multisite U.S. study comparing the clinical performance of the first U.S. Food and Drug Administration (FDA)-authorized POC RT-PCR for detection of SARS-CoV-2 in 20 min, the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test, to the most widely used RT-PCR laboratory test, the cobas 68/8800 SARS-CoV-2 test. Clinical nasopharyngeal swab specimens from 444 patients with 357 evaluable specimens at five U.S. clinical laboratories were enrolled from 21 September 2020 to 23 October 2020. The overall agreement between the Liat and 68/8800 systems for SARS-CoV-2 diagnostics was 98.6% (352/357). Using Liat, positive percent agreement for SARS-CoV-2 was 100% (162/162) and the negative percent agreement was 97.4% (190/195). The Liat is an RT-PCR POC test that provides highly accurate SARS-CoV-2 results in 20 min with performance equivalent to that of high-throughput laboratory molecular testing. Rapid RT-PCR testing at the POC can enable more timely infection control and individual care decisions for coronavirus disease 2019.

Commercial Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Molecular Assays: Superior Analytical Sensitivity of cobas SARS-CoV-2 Relative to NxTAG CoV Extended Panel and ID NOW COVID-19 Test.

CONTEXT.­: We implemented multiple nucleic acid amplification test platforms because of the limited availability of test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the early stages of the pandemic. Interpretation of results generated by different platforms and prioritization for testing algorithms required cross-comparison. OBJECTIVE.­: To compare the analytical sensitivity of 3 commercial SARS-CoV-2 molecular assays, selected samples were studied in parallel with Cobas SARS-CoV-2 test, NxTAG CoV Extended Panel, and ID NOW COVID-19 assays. DESIGN.­: A total of 8043 SARS-CoV-2 tests performed from March 22 to April 19, 2020, were included in this study. For all 1794 positive specimens detected by the cobas SARS-CoV-2 assay, the cycle threshold (Ct) values were manually tracked and plotted to demonstrate the distribution of sample viral levels. Additionally, 50 and 63 low-positive specimens (Ct values >32) as well as 50 and 61 consecutive positive specimens by the cobas assay were tested with NxTAG and ID NOW, respectively, to estimate their relative sensitivities. RESULTS.­: The Ct values of cobas SARS-CoV-2-positive samples were evenly distributed throughout ranges of 13.32 to 39.50 (mean, 25.06) and 13.60 to 42.49 (mean, 26.45) for ORF1 and E gene targets, respectively. NxTAG reliably detected only specimens with E gene Ct values lower than 33, and is estimated to detect 89.4% of positive specimens detected by cobas assay. ID NOW had performance variation independent of Ct value and is estimated to detect 83.5% of cobas positives. CONCLUSIONS.­: Clinical specimens exhibit a wide range of viral burden, with a significant portion at low levels. Analytical sensitivity of testing platforms is critical for reliable detection of SARS-CoV-2 and uniform care to patients.

Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke.

BACKGROUND: Emergence of the novel corona virus (severe acute respiratory syndrome (SARS)-CoV-2) in December 2019 has led to the COVID-19 pandemic. The extent of COVID-19 involvement in the central nervous system is not well established, and the presence or the absence of SARS-CoV-2 particles in the cerebrospinal fluid (CSF) is a topic of debate. CASE DESCRIPTION: We present two patients with COVID-19 and concurrent neurological symptoms. Our first patient is a 31-year-old man who had flu-like symptoms due to COVID-19 and later developed an acute-onset severe headache and loss of consciousness and was diagnosed with a Hunt and Hess grade 3 subarachnoid haemorrhage from a ruptured aneurysm. Our second patient is a 62-year-old woman who had an ischaemic stroke with massive haemorrhagic conversion requiring a decompressive hemicraniectomy. Both patients' CSF was repeatedly negative on real-time PCR analysis despite concurrent neurological disease. CONCLUSION: Our report shows that patients' CSF may be devoid of viral particles even when they test positive for COVID-19 on a nasal swab. Whether SARS-CoV-2 is present in CSF may depend on the systemic disease severity and the degree of the virus' nervous tissue tropism and should be examined in future studies.