Oral Liushen pill for patients with COVID-19: A prospective randomized controlled trial.

We examined the efficacy and safety of Liushen pill combined with basic treatment for patients with COVID-19. In total, 181 patients hospitalized with COVID-19, classified as asymptomatic mild type, were randomly divided into the experimental (n = 91) and control (n = 90) groups and were administered placebo (Maizao decoction) and Maizao decoction and Liushen pill, in addition to standard care, respectively. The negative conversion rate of nucleic acid (Day 7), hospital discharge rate (Days 8, 10, and 14), symptom disappearance rate (Days 3, 5, and 7), inflammatory cytokine levels, and adverse events were compared between the groups. The negative viral conversion rate was significantly higher in the experimental than in the control group (48.35 vs. 31.11%, p < 0.05). Subgroup analysis showed a similar significant trend when the Ct value was ≤30 at baseline. After 10 days, the hospital discharge rate was significantly higher in the experimental than in the control group (69.23 vs. 53.33%, p < 0.05). After 3-day medication, the headache symptoms significantly disappeared in the experimental (88.57%) compared to the control group (63.33%) (p < 0.05). After 5 days, the symptom disappearance rates of headache and cough were significantly higher in the experimental (97.14%) than in the control group (97.14 vs. 80.00, p < 0.05; 82.65 vs. 58.93%, p < 0.01, respectively). Posttreatment, the procalcitonin level was significantly lower in the experimental than in the control group (0.09 ± 0.00 vs. 0.14 ± 0.05 ng/L; p < 0.05). There were no significant between-group differences in clinical safety test indices. Early intervention with Liushen pill improved cough and headache and increased negative viral conversion and discharge rate.

Effect of liushen capsules (pill) on antiviral activity of COVID-19 in vitro and in patients with positive nucleic acid for more than 14 days

Objective To observe the efficacy and safety Liushen Capsules(Pill,LSP) combined with basic therapy on patients with coronavirus disease 2019(COVID-19) and positive nucleic acid for more than 14 days, and to test the in vitro antiviral effect of LSP. Methods To test the in vitro antiviral effect against the omicron(B.1.1.529) variant, its half-maximal inhibitory concentration(IC50) was determined by cytopathic effect test. The protocol was registered in Chinese Clinical Trial Registry(No. ChiCTR2200057532). Totally 50 patients who tested positive for severe acute respiratory syndrome coronavirus 2(SARSCoV-2), who were asymptomatic or had mild symptoms, were randomly divided into experimental group(26 cases) and control group(24 cases). The control group was given a basic treatment, and the experimental group was given LSP in conjunction with the basis treatment. The average negative time, negative conversion rate, immunological indices(IgG,IgM), and adverse events during treatment were compared between the two groups. Results The IC50 of LSP against SARS-CoV-2(omicron strain)was 0.194 8 g/mL. The average negative time of the virus in the experimental group [(5.03+or-2.41)d] was significantly lower than that in the control group [(6.46 +or-2.32)d,P<0.05]. After five days treatment, the negative conversion rate of the experimental group [57.36%(15/26)] was significantly lower than that of the control group [57.36%(15/26),P<0.05]. During the treatment, the negative conversion rate of the experimental group was always higher than that of the control group(P< 0.05). There was no significant difference in adverse reactions between the two groups(P>0.05). Conclusions LSP have an antiviral effect on SARS-CoV-2 in vitro, combined with basic therapy has certain curative effects on patients with positive nucleic acid for more than 14 days, and it can significantly shorten the negative conversion time of nucleic acid and negative rate, and improve the immune function of patients.

A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein.

The emerging SARS-CoV-2 variants, commonly with many mutations in S1 subunit of spike (S) protein are weakening the efficacy of the current vaccines and antibody therapeutics. This calls for the variant-proof SARS-CoV-2 vaccines targeting the more conserved regions in S protein. Here, we designed a recombinant subunit vaccine, HR121, targeting the conserved HR1 domain in S2 subunit of S protein. HR121 consisting of HR1-linker1-HR2-linker2-HR1, is conformationally and functionally analogous to the HR1 domain present in the fusion intermediate conformation of S2 subunit. Immunization with HR121 in rabbits and rhesus macaques elicited highly potent cross-neutralizing antibodies against SARS-CoV-2 and its variants, particularly Omicron sublineages. Vaccination with HR121 achieved near-full protections against prototype SARS-CoV-2 infection in hACE2 transgenic mice, Syrian golden hamsters and rhesus macaques, and effective protection against Omicron BA.2 infection in Syrian golden hamsters. This study demonstrates that HR121 is a promising candidate of variant-proof SARS-CoV-2 vaccine with a novel conserved target in the S2 subunit for application against current and future SARS-CoV-2 variants.

Exosomal Vaccine Loading T Cell Epitope Peptides of SARS-CoV-2 Induces Robust CD8+ T Cell Response in HLA-A Transgenic Mice.

Purpose: Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8+ T cell response. Methods: Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining. Results: The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-γ spot forming units and the frequencies of IFN-γ+/CD8+ T cells were 10-82-fold and 13-65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response. Conclusion: Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8+ T cell response in HLA-A transgenic mice.

Oral Liushen Pill for Patients with Covid-19 : A prospective, randomized, controlled trial (preprint)

Objective To analyze the efficacy and safety of Liushen Pill combined with basic treatment on patients with COVID-19.Methods One-hundred-eighty-one patients hospitalized with COVID-19, classified as asymptomatic, mild type, were randomly separated into the experimental (n=91) and control (n=90) groups. The control group was given placebo (Maizao decoction), while the experimental group was given Maizao decoction and Liushen pill, in addition to standard care. The negative conversion rate of nucleic acid (Day 7), hospital discharge rate (Day 8, 10, 14), symptom disappearance rate (Day 3, 5, 7), inflammatory cytokines and adverse events between the two groups were compared. Results The negative viral conversion rate in the experimental group was significantly higher than that in the control group (48.35% vs 31.11%, P＜0.05). Subgroup analysis showed a similar significant trend when the Ct value was ≤ 30 at baseline. After 10 days, the hospital discharge rate was significantly higher in the experimental than the control group (69.23% vs 53.33%, P＜0.05). After 3 days of medication, the headache symptoms significantly disappeared in the experimental group (88.57%) compared to the control group (63.33%) (P＜0.05). After 5 days, symptom disappearance rate of headache in the experimental group (97.14%) was still significantly higher than that in the control group (80.00%) (P＜0.05), as was the symptom disappearance rate of cough (82.65% vs 58.93%, P＜0.01). After treatment, the PCT level was significantly lower in the experimental than the control group (0.09±0.00 ng/L vs 0.14±0.05 ng/L) (P＜0.05). There were no significant between-groups differences in clinical safety test indexes.Conclusion Early intervention with Liushen Pill could improve the symptoms of cough and headache, and increase negative viral conversion and discharge rate.Trial registration Chinese Clinical Trial Registry, No. ChiCTR2200058859. Registered on April 18, 2022. https://www.chictr.org.cn/edit.aspx?pid=166975&htm=4

Impacts of COVID-19 on public transit ridership

In this paper, a national-wide study is conducted to investigate the impacts of COVID-19 on the public transit ridership in the top twenty metropolitan areas in the U.S. At first, COVID-19 composite index was developed to qualitatively measure the level of public fear toward COVID-19 in different metropolitan areas. After that, to analyze the impact of COVID-19 and some socioeconomic factors on transit ridership reduction during the COVID-19 pandemic, a random-effects panel data model was developed and the traditional correlation analysis was also conducted. According to the results of both analyses, it was found that the areas with higher median household income, a higher percentage of the population with a Bachelor’s degree or higher, higher employment rate, and a higher percentage of the Asian population are more likely to have more reductions in public transit ridership during the COVID-19 pandemic. On the other side, the areas with a higher percentage of the population in poverty, and a higher percentage of the Hispanic population are more likely to experience smaller reductions in public transit ridership.

Tubular epithelial cell-to-macrophage communication forms a negative feedback loop via extracellular vesicle transfer to promote renal inflammation and apoptosis in diabetic nephropathy.

Background: Macrophage infiltration around lipotoxic tubular epithelial cells (TECs) is a hallmark of diabetic nephropathy (DN). However, how these two types of cells communicate remains obscure. We previously demonstrated that LRG1 was elevated in the process of kidney injury. Here, we demonstrated that macrophage-derived, LRG1-enriched extracellular vesicles (EVs) exacerbated DN. Methods: We induced an experimental T2DM mouse model with a HFD diet for four months. Renal primary epithelial cells and macrophage-derived EVs were isolated from T2D mice by differential ultracentrifugation. To investigate whether lipotoxic TEC-derived EV (EVe) activate macrophages, mouse bone marrow-derived macrophages (BMDMs) were incubated with EVe. To investigate whether activated macrophage-derived EVs (EVm) induce lipotoxic TEC apoptosis, EVm were cocultured with primary renal tubular epithelial cells. Subsequently, we evaluated the effect of LRG1 in EVe by investigating the apoptosis mechanism. Results: We demonstrated that incubation of primary TECs of DN or HK-2 mTECs with lysophosphatidyl choline (LPC) increased the release of EVe. Interestingly, TEC-derived EVe activated an inflammatory phenotype in macrophages and induced the release of macrophage-derived EVm. Furthermore, EVm could induce apoptosis in TECs injured by LPC. Importantly, we found that leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EVe activated macrophages via a TGFßR1-dependent process and that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-enriched EVm induced apoptosis in injured TECs via a death receptor 5 (DR5)-dependent process. Conclusion: Our findings indicated a novel cell communication mechanism between tubular epithelial cells and macrophages in DN, which could be a potential therapeutic target.

How Chemists Achieve Active Learning Online During the COVID-19 Pandemic: Using the Community of Inquiry (Col) Framework to Support Remote Teaching

As numerous varsity campuses remain closed during the coronavirus disease 2019 pandemic, educators must look for suitable digital tools to conduct lessons and engage learners online. In this report, we discuss how to structure the online lessons using the Community of Inquiry framework (CoI). The CoI was applied to the university elective course Learning to Choose Better, taught by chemistry faculty. By using the appropriate digital tools in our course, we found success in achieving engagement, active learning, and team teaching. Until the world finds a resolution to the pandemic, online teaching will continue to be the new normal. Educators could view this time as a prime opportunity to experiment, innovate, and break new grounds in the realm of remote online teaching.