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.

Evaluation of efficacy and safety of Qiangzhu-qinggan formula as an adjunctive therapy in adult patients with severe influenza: study protocol for a randomized parallel placebo-controlled double-blind multicenter trial.

BACKGROUND: Influenza can fall into three categories according to severity: mild influenza, severe influenza, and critical influenza. Severe influenza can result in critical illness and sometimes death particularly in patients with comorbidities, advanced age, or pregnancy. Neuraminidase inhibitors (NAIs) are the only antiviral drugs in widespread use for influenza. However, the effectiveness of NAIs against severe influenza is uncertain. New effective drugs or regimens are therefore urgently needed. Qiangzhu-qinggan (QZQG) formula has been found to be effective against influenza virus infection during long-term application in China, which lacks support of evidence-based clinical trial till now. This study is designed to assess the efficacy and safety of QZQG formula as an adjuvant therapy in adult patients with severe influenza. METHODS: This protocol is drawn up in accordance with the SPIRIT guidelines and CONSORT Extension for Chinese herbal medicine formulas. This is a randomized, placebo-controlled, double-blind, multicenter trial. Two hundred twenty-eight adults with severe influenza are randomly assigned in a 1:1 ratio to QZQG or placebo for 7 days. All participants need to receive 1 day of screening before randomization, 7 days of intervention, and 21 days of observation after randomization. The primary outcome is the proportion of clinical improvement, defined as the proportion of patients who met the criteria of 3 points or less in the seven-category ordinal scale or 2 points or less in National Early Warning Score 2 within 7 days after randomization. DISCUSSION: This is the first randomized, controlled, parallel, double-blind clinical trial to evaluate the efficacy and safety of traditional Chinese herbal formula granules as an adjuvant therapy in adult patients with severe influenza. This study aims to redefine the value of traditional Chinese herbal medicines in the treatment of virus-related respiratory infectious diseases and serves as an example of evidence-based clinical trials of other Chinese herbal medicines.

How Does Multinational Corporations' CSR Influence Purchase Intention? The Role of Consumer Ethnocentrism and Consumer Ambivalence

Given the increasingly strained relationship between humans and the environment, green marketing has become a necessity for the sustainable development of society. In this context, this paper seeks to explore the influence of multinational enterprises' green marketing behavior on Chinese consumers' green consumption willingness. Through reviewing the related theories and deeply analyzing multinational corporations' CSR, a theoretical model of multinational corporations' CSR and consumer purchase intention has been built in this paper based on consumers' perceptions. The paper provides empirical research on the multinational corporations' CSR, corporate image, consumer ambivalence, and purchase intention, and offers a hypothesis of the relationship between the four. Consumer ethnocentrism can significantly negatively regulate the relationship between corporate image and consumers' willingness to buy and further negatively regulate the process of establishing the corporate social responsibility system of multinational corporations.

Amplification-Free Detection of SARS-CoV-2 Down to Single Virus Level by Portable Carbon Nanotube Biosensors.

The rapid and sensitive detection of trace-level viruses in a simple and reliable way is of great importance for epidemic prevention and control. Here, a multi-functionalized floating gate carbon nanotube field effect transistor (FG-CNT FET) based biosensor is reported for the single virus level detection of SARS-CoV-2 virus antigen and RNA rapidly with a portable sensing platform. The aptamers functionalized sensors can detect SARS-CoV-2 antigens from unprocessed nasopharyngeal swab samples within 1 min. Meanwhile, enhanced by a multi-probe strategy, the FG-CNT FET-based biosensor can detect the long chain RNA directly without amplification down to single virus level within 1 min. The device, constructed with packaged sensor chips and a portable sensing terminal, can distinguish 10 COVID-19 patients from 10 healthy individuals in clinical tests both by the RNAs and antigens by a combination detection strategy with an combined overall percent agreement (OPA) close to 100%. The results provide a general and simple method to enhance the sensitivity of FET-based biochemical sensors for the detection of nucleic acid molecules and demonstrate that the CNT FG FET biosensor is a versatile and reliable integrated platform for ultrasensitive multibiomarker detection without amplification and has great potential for point-of-care (POC) clinical tests.

Awareness and practice of preventive measures among healthcare workers in medical institutions in Beijing during influenza season on the eve of COVID-19 epidemic: A cross-sectional survey.

BACKGROUND: Influenza is an acute respiratory infectious disease caused by the influenza virus, which poses a certain threat to humans due to its short incubation period, fast transmission and strong infectivity. OBJECTIVES: To evaluate the awareness and prevention behavior against influenza among healthcare workers on the eve of the coronavirus disease 2019 (COVID-19) epidemic in Beijing, China. MATERIAL AND METHODS: Using the cross-sectional research design based on the principle of convenience sampling, an online questionnaire survey on the knowledge of flu, vaccination, medical protection behavior, and flu medication was conducted between January and February 2020. Healthcare workers from different healthcare facilities and different job positions in Beijing participated in this survey. RESULTS: A total of 1910 healthcare workers from different medical institutions and jobs were included in the study. The mean age of the participants was 32.69 ±8.72 years (range: 18-64 years). There were significant differences in knowledge about clinical signs about flu and prevention approaches among different age groups, individuals with different work experience and job titles (χ2 = 8.903-32.839; p < 0.05). Personnel with different job positions and education levels differed only in the knowledge about clinical signs of flu and identification of high-risk populations. A multivariate logistic regression analysis revealed that age (odds ratio (OR) = 0.979, 95% confidence interval (95% CI): 0.966-0.992) and education level (OR = 0.736, 95% CI: 0.588-0.921) were risk factors for hand hygiene practices, whereas job position (OR = 1.757, 95% CI: 1.146-2.695) and awareness of high-risk populations (OR = 1.405, 95% CI: 1.096-1.800) were protective factors influencing hand hygiene practices (p < 0.05). The only factor influencing mask wearing was the education level (OR = 0.610, 95% CI: 0.450-0.828). CONCLUSION: The knowledge level and preventive behavior of healthcare workers before the outbreak of COVID-19 has been insufficient.

Therapeutic potency of compound RMY-205 for pulmonary fibrosis induced by SARS-CoV-2 nucleocapsid protein.

Pulmonary fibrosis is a typical sequela of coronavirus disease 2019 (COVID-19), which is linked with a poor prognosis for COVID-19 patients. However, the underlying mechanism of pulmonary fibrosis induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 induced pulmonary fibrosis by activating pulmonary fibroblasts. N protein interacted with the transforming growth factor ß receptor I (TßRI), to disrupt the interaction of TßRI-FK506 Binding Protein12 (FKBP12), which led to activation of TßRI to phosphorylate Smad3 and boost expression of pro-fibrotic genes and secretion of cytokines to promote pulmonary fibrosis. Furthermore, we identified a compound, RMY-205, that bound to Smad3 to disrupt TßRI-induced Smad3 activation. The therapeutic potential of RMY-205 was strengthened in mouse models of N protein-induced pulmonary fibrosis. This study highlights a signaling pathway of pulmonary fibrosis induced by N protein and demonstrates a novel therapeutic strategy for treating pulmonary fibrosis by a compound targeting Smad3.

Adjuvant-Free COVID-19 Vaccine with Glycoprotein Antigen Oxidized by Periodate Rapidly Elicits Potent Immune Responses.

Modification of antigens to improve their immunogenicity represents a promising direction for the development of protein vaccine. Here, we designed facilely prepared adjuvant-free vaccines in which the N-glycan of SARS-CoV-2 receptor-binding domain (RBD) glycoprotein was oxidized by sodium periodate. This strategy only minimally modifies the glycans and does not interfere with the epitope peptides. The RBD glycoprotein oxidized by high concentrations of periodate (RBDHO) significantly enhanced antigen uptake mediated by scavenger receptors and promoted the activation of antigen-presenting cells. Without any external adjuvant, two doses of RBDHO elicited 324- and 27-fold increases in IgG antibody titers and neutralizing antibody titers, respectively, compared to the unmodified RBD antigen. Meanwhile, the RBDHO vaccine could cross-neutralize all of the SARS-CoV-2 variants of concern. In addition, RBDHO effectively enhanced cellular immune responses. This study provides a new insight for the development of adjuvant-free protein vaccines.

How Do Repeated Viewings in Forest Landscapes Influence Young People's Visual Behaviors and Cognitive Evaluations?

BACKGROUND: With the spread of the COVID-19 epidemic, it has gradually become normal to periodically visit and enjoy forest landscape resources in the suburbs of cities. For designers and managers of forest landscapes, exploring change in the visual behaviors and cognitive evaluations of people who repeatedly view forest landscapes and the characteristics of this change will aid the design and sustainable utilization of forest landscape resources in the suburbs of cities. PURPOSE: From the perspective of users' preferences for forest landscape space, this study explored the changes in visual behavior characteristics and psychological preference characteristics for individuals who repeatedly view forest landscapes and their drivers under different preferences. METHODS: This study collected data from 52 graduate and undergraduate students. We used a difference test to compare the differences in the visual behavior coincidence degree and the changes in psychological evaluations; a descriptive statistical analysis to explore young peoples' likes and dislikes of landscape elements; and Spearman correlation analysis to explore the correlation between the psychological evaluations and visual behaviors. MAIN RESULTS: 1. At the second viewing, the participants' regression behavior tended to decrease for various spaces, and they were more inclined to view areas that they had not viewed before. In addition, at the second viewing, the degree of fixation behavior coincidence was generally low, and there were obvious differences across spaces; 2. The participants' feature evaluations and comprehensive evaluations for landscapes did not change significantly with their increased familiarity with the spaces; 3. There was a significant positive correlation between the participants' psychological evaluations of landscape stimuli and the degree of fixation coincidence when viewing the spaces, among which the rate of distant clarity and the degree of fixation behavior coincidence were significantly and positively correlated. Meanwhile, at the second viewing, the number of favorite elements in the lookout space, which belongs to high-preference spaces, noticeably increased.

Reconstructing early transmission networks of SARS-CoV-2 using a genomic mutation model.

The coronavirus disease 2019 (COVID-19) pandemic has greatly damaged human society, but the origins and early transmission patterns of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen remain unclear. Here, we reconstructed the transmission networks of SARS-CoV-2 during the first three and six months since its first report based on ancestor-offspring relationships using BANAL-52-referenced mutations. We explored the position (i.e., root, middle, or tip) of early detected samples in the evolutionary tree of SARS-CoV-2. In total, 6 799 transmission chains and 1 766 transmission networks were reconstructed, with chain lengths ranging from 1-9 nodes. The root node samples of the 1 766 transmission networks were from 58 countries or regions and showed no common ancestor, indicating the occurrence of many independent or parallel transmissions of SARS-CoV-2 when first detected (i.e., all samples were located at the tip position of the evolutionary tree). No root node sample was found in any sample ( n=31, all from the Chinese mainland) collected in the first 15 days from 24 December 2019. Results using six-month data or RaTG13-referenced mutation data were similar. The reconstruction method was verified using a simulation approach. Our results suggest that SARS-CoV-2 may have already been spreading independently worldwide before the outbreak of COVID-19 in Wuhan, China. Thus, a comprehensive global survey of human and animal samples is essential to explore the origins of SARS-CoV-2 and its natural reservoirs and hosts.

Identification of and Mechanistic Insights into SARS-CoV-2 Main Protease Non-Covalent Inhibitors: An In-Silico Study.

The indispensable role of the SARS-CoV-2 main protease (Mpro) in the viral replication cycle and its dissimilarity to human proteases make Mpro a promising drug target. In order to identify the non-covalent Mpro inhibitors, we performed a comprehensive study using a combined computational strategy. We first screened the ZINC purchasable compound database using the pharmacophore model generated from the reference crystal structure of Mpro complexed with the inhibitor ML188. The hit compounds were then filtered by molecular docking and predicted parameters of drug-likeness and pharmacokinetics. The final molecular dynamics (MD) simulations identified three effective candidate inhibitors (ECIs) capable of maintaining binding within the substrate-binding cavity of Mpro. We further performed comparative analyses of the reference and effective complexes in terms of dynamics, thermodynamics, binding free energy (BFE), and interaction energies and modes. The results reveal that, when compared to the inter-molecular electrostatic forces/interactions, the inter-molecular van der Waals (vdW) forces/interactions are far more important in maintaining the association and determining the high affinity. Given the un-favorable effects of the inter-molecular electrostatic interactions-association destabilization by the competitive hydrogen bond (HB) interactions and the reduced binding affinity arising from the un-compensable increase in the electrostatic desolvation penalty-we suggest that enhancing the inter-molecular vdW interactions while avoiding introducing the deeply buried HBs may be a promising strategy in future inhibitor optimization.

Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D.

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation.

pH-Sensitive and Biodegradable Mn3(PO4)2·3H2O Nanoparticles as an Adjuvant of Protein-Based Bivalent COVID-19 Vaccine to Induce Potent and Broad-Spectrum Immunity.

Developing a novel and potent adjuvant with great biocompatibility for immune response augmentation is of great significance to enhance vaccine efficacy. In this work, we prepared a long-term stable, pH-sensitive, and biodegradable Mn3(PO4)2·3H2O nanoparticle (nano-MnP) by simply mixing MnCl2/NaH2PO4/Na2HPO4 solution for the first time and employed it as an immune stimulant in the bivalent COVID-19 protein vaccine comprised of wild-type S1 (S1-WT) and Omicron S1 (S1-Omicron) proteins as antigens to elicit a broad-spectrum immunity. The biological experiments indicated that the nano-MnP could effectively activate antigen-presenting cells through the cGAS-STING pathway. Compared with the conventional Alum-adjuvanted group, the nano-MnP-adjuvanted bivalent vaccine elicited approximately 7- and 8-fold increases in IgG antibody titers and antigen-specific IFN-γ secreting T cells, respectively. Importantly, antisera of the nano-MnP-adjuvanted group could effectively cross-neutralize the SARS-CoV-2 and its five variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron, demonstrating that this bivalent vaccine based on S1-WT and S1-Omicron proteins is an effective vaccine design strategy to induce broad-spectrum immune responses. Collectively, this nano-MnP material may provide a novel and efficient adjuvant platform for various prophylactic and therapeutic vaccines and provide insights for the development of the next-generation manganese adjuvant.

Novel sialoglycan linkage for constructing adjuvant-protein conjugate as potent vaccine for COVID-19.

Self-adjuvanting protein vaccines have been proved to be highly immunogenic with efficient codelivery of adjuvant and antigen. Current protein vaccines with built-in adjuvants are all modified at the peptide backbone of antigen protein, which could not achieve minor epitope interference and adjuvant multivalency at the same time. Herein, we developed a new conjugate strategy to construct effective adjuvant-protein vaccine with adjuvant cluster effect and minimal epitope interference. The toll-like receptor 7 agonist (TLR7a) is covalently conjugated on the terminal sialoglycans of SARS-CoV-2-S1 protein, leading to intracellular release of the small-molecule stimulators with greatly reduced risks of systemic toxicity. The resulting TLR7a-S1 conjugate elicited strong activation of immune cells in vitro, and potent antibody and cellular responses with a significantly enhanced Th1-bias in vivo. TLR7a-S1-induced antibody also effectively cross-neutralized all variants of concern. This sialoglycoconjugation approach to construct protein conjugate vaccines will have more applications to combat SARS-CoV-2 and other diseases.

Self-Adjuvanting Protein Vaccine Conjugated with a Novel Synthetic TLR4 Agonist on Virus-Like Liposome Induces Potent Immunity against SARS-CoV-2.

Exploring potent adjuvants and new vaccine strategies is crucial for the development of protein vaccines. In this work, we synthesized a new TLR4 agonist, structurally simplified lipid A analogue GAP112, as a potent built-in adjuvant to improve the immunogenicity of SARS-CoV-2 spike RBD protein. The new TLR4 agonist GAP112 was site-selectively conjugated on the N-terminus of RBD to construct an adjuvant-protein conjugate vaccine in a liposomal formulation. It is the first time that a TLR4 agonist is site-specifically and quantitatively conjugated to a protein antigen. Compared with an unconjugated mixture of GAP112/RBD, a two-dose immunization of the GAP112-RBD conjugate vaccine strongly activated innate immune cells, elicited a 223-fold increase in RBD-specific antibodies, and markedly enhanced T-cell responses. Antibodies induced by GAP112-RBD also effectively cross-neutralized SARS-CoV-2 variants (Delta/B.1.617.2 and Omicron/B.1.1.529). This conjugate strategy provides an effective method to greatly enhance the immunogenicity of antigen in protein vaccines against SARS-CoV-2 and other diseases.

Research on Enterprise Financial Risk Conduction Mechanism Based on System Dynamics

Affected by the COVID-19 pandemic and the economic situation, many enterprises have fallen into financial crisis. In order to explore the causes of enterprise financial risk and the conduction path of risk sources, this paper starts from the theory, characteristics, and path of financial risk conduction, combines Hall three-dimensional structure and system dynamics models, establishes the path of enterprise financial risk conduction (causality graph), and combines the value-at-risk VaR model to measure the risk. Based on this methodology, a three-dimensional multiple risk interaction and dynamic-static combination of an enterprise financial risk conduction model is established, aiming at identifying the sources of financial risk in different periods and providing timely risk control countermeasures to avoid financial crises. This paper does not refine some of the indicators and takes into account the probability of different scenarios and/or the number of trigger strategies to avoid or reduce risk. In the future, refining the indicators to include considerations such as production technology will enable a more robust model of corporate financial risk conduction.

Does ambient air quality standard contribute to green innovation of enterprises in China? Implications for environmental protection and public health

In the post-COVID-19 era, environmental pollution has been a serious threat to public health. Enterprises are in urgent need of enhancing green technology innovation as the main source of pollutant emissions, and it is necessary for governments to support green innovation of enterprises to reduce pollutant emissions and promote public health. In this context, this paper investigates whether the Ambient Air Quality Standard (AAQS) implemented in 2012 in China contributes to green innovation of enterprises, to provide implications for environmental protection and public health. By using panel data of Chinese A-share listed companies from 2008 to 2020, this study adopts the difference-in-difference model to analyze the policy impact of environmental regulation on green innovation of enterprises and its internal mechanism. The results show that AAQS has significantly improved the green innovation of enterprises. Furthermore, AAQS affects the green innovation of enterprises by virtue of two mechanism paths: compliance cost effect and innovation offset effect. On the one hand, AAQS leads to an increase in production costs of enterprises, thus inhibiting green innovation activities of enterprises. On the other hand, AAQS encourages enterprises to increase R&D investment in green technology, thus enhancing their green innovation. In addition, the impact of AAQS on firms' green innovation has heterogeneous characteristics. Our findings not only enrich the studies of environmental regulation and green innovation of enterprises but also provide policymakers in China and other developing countries with implications for environmental protection and public health improvement.

Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation. Graphical

Insight into core -shell microporous zinc silicate adsorbent to eliminate antibiotics in aquatic environment under the COVID-19 pandemic.

Under the new crown pneumonia (COVID-19) epidemic, the intensive use of therapeutic drugs has caused certain hidden danger to the safety of the water environment. Therefore, the core-shell microporous zinc silicate (SiO2@ZSO) was successfully prepared and used for the adsorption of chloroquine phosphate (CQ), tetracycline (TC) and ciprofloxacin (CIP) for eliminating the threat of COVID-19. The adsorption efficiencies of 20 mg L-1 of CQ, TC and CIP by SiO2@ZSO were all up to 60% after 5 min. The adsorption capacity of SiO2@ZSO for CQ, TC and CIP can reach 49.01 mg g-1, 56.06 mg g-1 and 104.77 mg g-1, respectively. The adsorption process is primarily physical adsorption, which is heterogeneous, spontaneous and preferential. Moreover, the effects of temperature, pH, salinity, and reusability on the adsorption of CQ, TC, and CIP on SiO2@ZSO were investigated. The adsorption mechanism mainly involves electrostatic attraction, partitioning and hydrogen bonding, which is insightful through the changes of the elements and functional groups before and after adsorption. This work provides a solution to the problems faced by the treatment of pharmaceuticals wastewater under the COVID-19 epidemic.

Real-world evaluation of the Stemoscope electronic tele-auscultation system.

BACKGROUND: With the spread of COVID-19, telemedicine has played an important role, but tele-auscultation is still unavailable in most countries. This study introduces and tests a tele-auscultation system (Stemoscope) and compares the concordance of the Stemoscope with the traditional stethoscope in the evaluation of heart murmurs. METHODS: A total of 57 patients with murmurs were recruited, and echocardiographs were performed. Three cardiologists were asked to correctly categorize heart sounds (both systolic murmur and diastolic murmur) as normal vs. abnormal with both the Stemoscope and a traditional acoustic stethoscope under different conditions. Firstly, we compared the in-person auscultation agreement between Stemoscope and the conventional acoustic stethoscope. Secondly, we compared tele-auscultation (recorded heart sounds) agreement between Stemoscope and acoustic results. Thirdly, we compared both the Stemoscope tele-auscultation results and traditional acoustic stethoscope in-person auscultation results with echocardiography. Finally, ten other cardiologists were asked to complete a qualitative questionnaire to assess their experience using the Stemoscope. RESULTS: For murmurs detection, the in-person auscultation agreement between Stemoscope and the acoustic stethoscope was 91% (p = 0.67). The agreement between Stemoscope tele-auscultation and the acoustic stethoscope in-person auscultation was 90% (p = 0.32). When using the echocardiographic findings as the reference, the agreement between Stemoscope (tele-auscultation) and the acoustic stethoscope (in-person auscultation) was 89% vs. 86% (p = 1.00). The system evaluated by ten cardiologists is considered easy to use, and most of them would consider using it in a telemedical setting. CONCLUSION: In-person auscultation and tele-auscultation by the Stemoscope are in good agreement with manual acoustic auscultation. The Stemoscope is a helpful heart murmur screening tool at a distance and can be used in telemedicine.