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.

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

Nebulized exosomes derived from allogenic adipose tissue mesenchymal stromal cells in patients with severe COVID-19: a pilot study.

BACKGROUND: Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. METHODS: The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. RESULTS: Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. CONCLUSIONS: Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. TRIAL REGISTRATION: MEXCOVID, NCT04276987.

Using refined kano model and decision trees to discover learners' needs for teaching videos.

With the advancement of technology and the spread of the COVID19 epidemic, learning can no longer only be done through face-to-face teaching. Numerous digital learning materials have appeared in large numbers, changing people's learning mode. In the era of information explosion, how to capture the learners' attention to teaching videos and improve learning effectiveness is the common goal of every designer of e-leaning teaching content. Previous researches focused on the analysis of learning effectiveness and satisfaction. Instructional designers only provided design elements with high learning effectiveness or high satisfaction, and lacked in-depth analysis of the learners' perspectives. The opinions of these e-learning users are often the key to the success of online teaching videos. Therefore, this study aims at the design elements that will be used in the teaching film. The operation mode of the piano mechanism will be employed as the content of the teaching film. Based on eight elements including arrow cueing, dynamic arrow cueing, spreading-color cueing, contrary to cueing, font style, color application, anthropomorphic, and audiovisual complementarity, we use Refined Kano Model to analyze learners' needs of categorization of each element, and discover learners' expectations for teaching videos. In addition, this study also conducts in-depth data analysis through decision trees algorithm, and stratification analyses using different variables (such as design expertise, using frequency, and usage experience, etc.) to find out the key design factors that affect learners' learning. Depending on the learner's background, the use of e-learning experience, using frequency, and the length of the learning video, our results could provide for reference when designing teaching videos. Instructional designers can better understand how to effectively use design elements, so that the teaching videos can achieve the best learning effect.

Sludge Disinfection, Reduction and Energy Recovery by Anaerobic Digestion with Thermal Hydrolysis Pretreatment

The disinfection of sewage sludge has become a hot focus due to the outbreak of COVID-19, which belongs to one aspect of sludge harmless treatment. However, the threat of sludge to the environment is not only caused by harmful microbes. It is necessary to explore energy recovery and resource utilization of sludge treatment that is based on harmlessness, volume reduction and stabilization. Various advanced technologies were integrated to build an advanced anaerobic digestion system in Beijing urban area, which has achieved a good sludge treatment effect in the past three years since its construction and operation. Thermal hydrolysis can effectively inactivate harmful microorganisms, the hygienic properties of advanced anaerobic digestion products can meet the standard, and its heavy metals contents are significantly lower than the related standard limit, which have changed to more stable forms. The unit treatment capacity of digester increased to 3.6 times that of conventional anaerobic digestion due to the modification effect of thermal hydrolysis on sludge properties, saving about 68% investment in digester construction. The degradation rate of organics increased from 40% to 52%, indicating that the stability of the digestion products was further improved, the residual solids were further reduced with the volume reduction rate of sludge increased from 28% to 66%. The biogas production rate was greatly increased with the improvement of organic conversion efficiency. Even operated below capacity, the advanced anaerobic digestion system still had the capacity to output 4 089×10~4 kW·h power under the condition that deducting the heat and power consumption of the system itself from the energy recovered. The treatment and disposal process of sludge were successfully connected by the resource utilization of advanced anaerobic digestion products. The large-scale production application in Beijing has created a successful and mature engineering reference for sludge advanced anaerobic digestion.

An Engineered Receptor-Binding Domain Improves the Immunogenicity of Multivalent SARS-CoV-2 Vaccines.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein mediates viral entry into cells expressing angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino-acid fragment of the 1,273-amino-acid S-protein protomer. The RBD is the primary SARS-CoV-2 neutralizing epitope and a critical target of any SARS-CoV-2 vaccine. Here, we show that this RBD conjugated to each of two carrier proteins elicited more potent neutralizing responses in immunized rodents than did a similarly conjugated proline-stabilized S-protein ectodomain. Nonetheless, the native RBD is expressed inefficiently, limiting its usefulness as a vaccine antigen. However, we show that an RBD engineered with four novel glycosylation sites (gRBD) is expressed markedly more efficiently and generates a more potent neutralizing responses as a DNA vaccine antigen than the wild-type RBD or the full-length S protein, especially when fused to multivalent carriers, such as a Helicobacter pylori ferritin 24-mer. Further, gRBD is more immunogenic than the wild-type RBD when administered as a subunit protein vaccine. Our data suggest that multivalent gRBD antigens can reduce costs and doses, and improve the immunogenicity, of all major classes of SARS-CoV-2 vaccines.IMPORTANCE All available vaccines for coronavirus disease 2019 (COVID-19) express or deliver the full-length SARS-CoV-2 spike (S) protein. We show that this antigen is not optimal, consistent with observations that the vast majority of the neutralizing response to the virus is focused on the S-protein receptor-binding domain (RBD). However, this RBD is not expressed well as an independent domain, especially when expressed as a fusion protein with a multivalent scaffold. We therefore engineered a more highly expressed form of the SARS-CoV-2 RBD by introducing four glycosylation sites into a face of the RBD normally occluded in the full S protein. We show that this engineered protein, gRBD, is more immunogenic than the wild-type RBD or the full-length S protein in both genetic and protein-delivered vaccines.

Impact of the COVID-19 pandemic on intention to use traditional Chinese medicine: A cross-sectional study based on the theory of planned behavior.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has become an increasingly severe public health emergency. Although traditional Chinese medicine (TCM) has helped to combat COVID-19, public perception of TCM remains controversial. We used the theory of planned behavior (TPB) to identify factors that affect the intention to use TCM. METHODS: A cross-sectional web-based survey of 10,824 individuals from the general public was conducted between March 16 and April 2, 2020. The participants were recruited using a snowball sampling method. Data were collected using a self-administered questionnaire, based on the TPB. The questionnaire consisted of demographic characteristics and TPB structures. Structural equation modeling was used to identify predictors of intention. RESULTS: The results indicated the model explained 77.5% and 71.9% of intention and attitude variance. Intention to use TCM had the strongest relationship with attitude (P < 0.001), followed by past behavior (P < 0.001), subjective norms (P < 0.001) and perceived behavioral control (P < 0.001). Attitudes toward TCM were significantly affected by perceived behavioral control (P < 0.001), subjective norms (P < 0.001) and cognition of TCM (P < 0.001). CONCLUSION: Attitude is a key factor in determining the intention to use TCM, followed by past behaviors, subjective norms and perceived behavioral control. Our results offer important implications for health policy makers to promote the use of TCM.

Vaginal delivery report of a healthy neonate born to a convalescent mother with COVID--19.

The outbreak of the infection of 2019 novel coronavirus disease (COVID--19) has become a challenging public health threat worldwide. Limited data are available for pregnant women with COVID-19 pneumonia. We report a case of a convalescing pregnant woman diagnosed with COVID-19 infection 37 days before delivery in the third trimester. A live birth without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was performed successfully via the vagina. The findings from our case indicate that there is no intrauterine transmission in this woman who developed COVID-19 pneumonia in late pregnancy.