New Insights into Vibrio cholerae Biofilms from Molecular Biophysics to Microbial Ecology.

With the discovery that 48% of cholera infections in rural Bangladesh villages could be prevented by simple filtration of unpurified waters and the detection of Vibrio cholerae aggregates in stools from cholera patients it was realized V. cholerae biofilms had a central function in cholera pathogenesis. We are currently in the seventh cholera pandemic, caused by O1 serotypes of the El Tor biotypes strains, which initiated in 1961. It is estimated that V. cholerae annually causes millions of infections and over 100,000 deaths. Given the continued emergence of cholera in areas that lack access to clean water, such as Haiti after the 2010 earthquake or the ongoing Yemen civil war, increasing our understanding of cholera disease remains a worldwide public health priority. The surveillance and treatment of cholera is also affected as the world is impacted by the COVID-19 pandemic, raising significant concerns in Africa. In addition to the importance of biofilm formation in its life cycle, V. cholerae has become a key model system for understanding bacterial signal transduction networks that regulate biofilm formation and discovering fundamental principles about bacterial surface attachment and biofilm maturation. This chapter will highlight recent insights into V. cholerae biofilms including their structure, ecological role in environmental survival and infection, regulatory systems that control them, and biomechanical insights into the nature of V. cholerae biofilms.

Chemical composition characteristics and source analysis of PM2.5 in Jiaxing, China: Insights into the effect of COVID-19 outbreak.

Jiaxing is a medium-sized city in the Yangtze River Delta (YRD), which showed complex local and surrounding pollution sources. To study the COVID-19 impact on the ambient PM2.5 in Jiaxing, we collected the PM2.5 samples from January 2 to April 25, 2020 and analyzed their chemical compositions (including carbon components, water-soluble ions (WSIs), and inorganic elements). The concentration of PM2.5 was 83.13 ± 30.93 µg/m3 before COVID-19 pandemic, and then remarkably decreased with COVID-19 outbreak due to the suspension of mobility and industrial activities. Meanwhile, the concentrations of main chemical species (carbon components, water-soluble ions and inorganic elements) of PM2.5 all decreased from period A (January 2 to 20, 2020) to period B (January 23 to February 10, 2020). Moreover, Trajectory clustering analysis showed that close-range transport was one of the dominant factors throughout all the period, except for period D (April 1 to 25, 2020). In addition, PSCF model indicated that the COVID-19 outbreak resulted in a significant decrease of WPSCF value. This study highlighted the differences in chemical compositions and sources of PM2.5 since COVID-19 pandemic were reported and provide a better understanding of the impact of COVID-19 outbreak on PM2.5.

From Health Campaign to Interpersonal Communication: Does Traditional Diet Culture Hinder the Communication of the Chinese Gongkuai Campaign?

Interpersonal communication is beneficial in promoting individuals' tendency to accept health-campaign-targeted behavior. Based on the protective action decision model, this study investigated the key factors underlying individual's interpersonal communication on the Gongkuai campaign, which was carried out during Coronavirus disease 2019 (COVID-19). The main goal of the Gongkuai campaign was to change traditional communal eating habits and reduce public health risks. An online questionnaire survey involving 618 respondents was conducted in China after the 2020 Gongkuai campaign propagated, and the data were analyzed by using the structural equation modeling technique. The results indicated that health campaign exposure is a critical determinant of perceived campaign-related knowledge and health risk perception, which are significant predictors of interpersonal communication. Meanwhile, campaign-related knowledge can elicit risk perception. Furthermore, campaign exposure influenced interpersonal communication in ways that traditional diet culture did not predict. Risk perception was also unaffected by traditional diet culture. It is worth noting that individuals' agreement with traditional diet culture does not hinder health campaign-generated interpersonal communication in the context of public health crisis. Based on the findings, theoretical and policy implications for motivating interpersonal communication were discussed, and research limitations were pointed out.

Black swan event small-sample transfer learning (BEST-L) and its case study on electrical power prediction in COVID-19

The black swan event will usually cause a great impact on the normal operation of society. The scarcity of such events leads to a lack of relevant data and challenges in dealing with related problems. Different situations also make the traditional methods invalid. In this paper, a transfer learning framework and a convolutional neuron network are proposed to deal with the black swan small-sample events (BEST-L). Taking the COVID-19 as a typical black swan event, the BEST-L is utilized to achieve accurate mid-term load forecasting using the relationship between economy and electricity consumption. The experiment results show that the transfer learning model can effectively learn the basic knowledge about the relationship between the adopted input and output data and use a relatively small amount of data during the black swan event to improve the target areas' generalization. The approach and results can provide an effective approach to respond and react to sudden changes quickly and effectively in similar open problems.

The Role of Computer Remote Monitoring Technology for Nursing Care in Elderly Breast Cancer Complications.

Geriatric patients undergoing mastectomy have a weakened organism and slow recovery of gastrointestinal function after surgery, which may lead to various complications, affect the absorption of intestinal nutrients, and prolong the healing rate of wounds. Therefore, it is necessary to find an effective nursing program to promote the recovery of gastrointestinal function and prevent postoperative complications in elderly patients undergoing mastectomy. With the continuous development and advancement of computer and communication technologies, telecare is gaining more and more attention and has become an important part of medical information technology construction. Falls endanger the elderly and other special populations, especially after a sudden but unassisted fall, which may be life-threatening. Timely fall detection and rescue can win valuable time for treatment and rescue, which is very important to protect users' health and improve medical monitoring. In order to provide better medical care to the elderly population and reduce the harm caused by falls, this paper will focus on the fall problem of the elderly in telecare. In order to facilitate the detection of falls of the elderly, we design an Android sensor-based data acquisition scheme, using the built-in acceleration sensor in the Android system to collect the human acceleration information, and through the JMS middleware technology, the collected data are transmitted to MATLAB for analysis and processing in real time. This paper preprocesses and synthesizes the collected human body data and visualizes the acceleration changes of various typical daily activities of the human body and breast cancer, then extracts the relevant data features according to the synthesized SVM curve, constructs a pattern recognition algorithm using the extracted features, and verifies the effectiveness of the pattern recognition algorithm through experiments.

Novel phenotypes of coronavirus disease: a temperature-based trajectory model.

BACKGROUND: Coronavirus disease has heterogeneous clinical features; however, the reasons for the heterogeneity are poorly understood. This study aimed to identify clinical phenotypes according to patients' temperature trajectory. METHOD: A retrospective review was conducted in five tertiary hospitals in Hubei Province from November 2019 to March 2020. We explored potential temperature-based trajectory phenotypes and assessed patients' clinical outcomes, inflammatory response, and response to immunotherapy according to phenotypes. RESULTS: A total of 1580 patients were included. Four temperature-based trajectory phenotypes were identified: normothermic (Phenotype 1); fever, rapid defervescence (Phenotype 2); gradual fever onset (Phenotype 3); and fever, slow defervescence (Phenotype 4). Compared with Phenotypes 1 and 2, Phenotypes 3 and 4 had a significantly higher C-reactive protein level and neutrophil count and a significantly lower lymphocyte count. After adjusting for confounders, Phenotypes 3 and 4 had higher in-hospital mortality (adjusted odds ratio and 95% confidence interval 2.1, 1.1-4.0; and 3.3, 1.4-8.2, respectively), while Phenotype 2 had similar mortality, compared with Phenotype 1. Corticosteroid use was associated with significantly higher in-hospital mortality in Phenotypes 1 and 2, but not in Phenotypes 3 or 4 (p for interaction < 0.01). A similar trend was observed for gamma-globulin. CONCLUSIONS: Patients with different temperature-trajectory phenotypes had different inflammatory responses, clinical outcomes, and responses to corticosteroid therapy.

Interaction of serum proteins with SARS-CoV-2 RBD.

The outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a worldwide public health crisis. When the SARS-CoV-2 enters the biological fluids in the human body, different types of biomolecules (in particular proteins) may adsorb on its surface and alter its infection ability. Although great efforts have recently been devoted to the interaction of specific antibodies with the SARS-CoV-2, it still remains largely unknown how the other serum proteins affect the infection of the SARS-CoV-2. In this work, we systematically investigate the interaction of serum proteins with the SARS-CoV-2 RBD by molecular docking and all-atom molecular dynamics simulations. It is found that non-specific immunoglobulins (Ig) indeed cannot effectively bind to the SARS-CoV-2 RBD while human serum albumin (HSA) may have some potential in blocking its infection (to ACE2). More importantly, we find that the RBD can cause significant structural changes in Apolipoprotein E (ApoE), by which SARS-CoV-2 may hijack the metabolic pathway of ApoE to facilitate its cell entry. The present study enhances the understanding of the role of protein corona in the bio-behaviors of SARS-CoV-2, which may aid the more precise and personalized treatment for COVID-19 infection in the clinic.

Evaluating the Traditional Chinese Medicine (TCM) Officially Recommended in China for COVID-19 Using Ontology-Based Side-Effect Prediction Framework (OSPF) and Deep Learning.

ETHNOPHARMACOLOGICAL RELEVANCE: The novel coronavirus disease (COVID-19) outbreak in Wuhan has imposed a huge influence in terms of public health and economy on society. However, no effective drugs or vaccines have been developed so far. Traditional Chinese Medicine (TCM) has been considered as a promising supplementary treatment of this disease due to its clinically proven performance in many severe diseases, like severe acute respiratory syndrome (SARS). Meanwhile, many reports suggest that the side-effects (SE) of TCM prescriptions cannot be ignored in treating COVID-19 as it often leads to dramatic degradation of the patients' physical condition. Systematic evaluation of TCM regarding its latent SE becomes a burning issue. AIM: In this study, we used an ontology-based side-effect prediction framework (OSPF) developed from our previous work and Artificial Neural Network (ANN)-based deep learning, to evaluate the TCM prescriptions officially recommended by China for the treatment of COVID-19. MATERIALS AND METHODS: The OSPF developed from our previous work was implemented in this study, where an ontology-based model separated all ingredients in a TCM prescription into two categories: hot and cold. A database was created by converting each TCM prescription into a vector which contained ingredient dosages, corresponding hot/cold attribution and safe/unsafe labels. This allowed for training of the ANN model. A safety indicator (SI), as a complement to SE possibility, was then assigned to each TCM prescription. According to the proposed SI, from high to low, the recommended prescription list could be optimized. Furthermore, in interest of expanding the potential treatment options, SIs of other well-known TCM prescriptions, which are not included in the recommended list but are used traditionally to cure flu-like diseases, are also evaluated via this method. RESULTS: Based on SI, QFPD-T, HSBD-F, PMSP, GCT-CJ, SF-ZSY, and HSYF-F were the safest treatments in the recommended list, with SI scores over 0.8. PESP, QYLX-F, JHQG-KL, SFJD-JN, SHL-KFY, PESP1, XBJ-ZSY, HSZF-F, PSSP2, FFTS-W, and NHSQ-W were the prescriptions most likely to be unsafe, with SI scores below 0.1. In the additional lists of other TCM prescriptions, the indicators of XC-T, SQRS-S, CC-J, and XFBD-F were all above 0.8, while QF-Y, XZXS-S, BJ-S, KBD-CJ, and QWJD-T's indicators were all below 0.1. CONCLUSIONS: In total, there were 10 TCM prescriptions with indicators over 0.8, suggesting that they could be considered in treating COVID-19, if suitable. We believe this work could provide reasonable suggestions for choosing proper TCM prescriptions as a supplementary treatment for COVID-19. Furthermore, this work introduces a novel and informative method which could help create recommendation list of TCM prescriptions for the treatment of other diseases.

Construction and Immunogenicity Comparison of Three Virus-Like Particles Carrying Different Combinations of Structural Proteins of Avian Coronavirus Infectious Bronchitis Virus.

Infectious bronchitis virus (IBV) poses massive economic losses in the global poultry industry. Here, we firstly report the construction and immunogenicity comparison of virus-like particles (VLPs) carrying the S, M and E proteins (SME-VLPs); VLPs carrying the S and M proteins (SM-VLPs); and VLPs carrying the M and E proteins (ME-VLPs) from the dominant serotype representative strain GX-YL5 in China. The neutralizing antibody response induced by the SME-VLPs was similar to that induced by the inactivated oil vaccine (OEV) of GX-YL5, and higher than those induced by the SM-VLPs, ME-VLPs and commercial live vaccine H120. More importantly, the SME-VLPs elicited higher percentages of CD4+ and CD8+ T lymphocytes than the SM-VLPs, ME-VLPs and OEV of GX-YL5. Compared with the OEV of GX-YL5, higher levels of IL-4 and IFN-γ were also induced by the SME-VLPs. Moreover, the mucosal immune response (sIgA) induced by the SME-VLPs in the tear and oral swabs was comparable to that induced by the H120 vaccine and higher than that induced by the OEV of GX-YL5. In the challenge experiment, the SME-VLPs resulted in significantly lower viral RNA levels in the trachea and higher protection scores than the OEV of GX-YL5 and H120 vaccines, and induced comparable viral RNA levels in the kidneys, and tear and oral swabs to the OEV of GX-YL5. In summary, among the three VLPs, the SME-VLPs carrying the S, M and E proteins of IBV could stimulate the strongest humoral, cellular and mucosal immune responses and provide effective protection, indicating that it would be an attractive vaccine candidate for IB.

Protein corona critically affects the bio-behaviors of SARS-CoV-2 (preprint)

The outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a worldwide public health crisis. When the SARS-CoV-2 enters the biological fluids in the human body, different types of biomolecules (in particular proteins) may adsorb on its surface and alter its infection ability. Although great efforts have recently been devoted to the interaction of the specific antibodies with the SARS-CoV-2, it still remains largely unknown how the other serum proteins affect the infection of the SARS-CoV-2. In this work, we systematically investigate the interaction of serum proteins with the SARS-CoV-2 RBD by the molecular docking and the all-atom molecular dynamics simulations. It is found that the non-specific immunoglobulin (Ig) indeed cannot effectively bind to the SARS-CoV-2 RBD while the human serum albumin (HSA) may have some potential of blocking its infection (to ACE2). More importantly, we find that the RBD can cause the significant structural change of the Apolipoprotein E (ApoE), by which SARS-CoV-2 may hijack the metabolic pathway of the ApoE to facilitate its cell entry. The present study enhances the understanding of the role of protein corona in the bio-behaviors of SARS-CoV-2, which may aid the more precise and personalized treatment for COVID-19 infection in the clinic.

Accurate Evaluation on the Interactions of SARS-CoV-2 with Its Receptor ACE2 and Antibodies CR3022/CB6 (preprint)

The spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a global health crisis. The binding affinity of SARS-CoV-2 (in particular the receptor binding domain, RBD) to its receptor angiotensin converting enzyme 2 (ACE2) and the antibodies is of great importance in understanding the infectivity of COVID-19 and evaluating the candidate therapeutic for COVID-19. In this work, we propose a new method based on molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) to accurately calculate the free energy of SARS-CoV-2 RBD binding to ACE2 and antibodies. The calculated binding free energy of SARS-CoV-2 RBD to ACE2 is -13.3 kcal/mol, and that of SARS-CoV RBD to ACE2 is -11.4 kcal/mol, which agrees well with experimental result (-11.3 kcal/mol and -10.1 kcal/mol, respectively). Moreover, we take two recently reported antibodies as the example, and calculate the free energy of antibodies binding to SARS-CoV-2 RBD, which is also consistent with the experimental findings. Further, within the framework of the modified MM/PBSA, we determine the key residues and the main driving forces for the SARS-CoV-2 RBD/CB6 interaction by the computational alanine scanning method. The present study offers a computationally efficient and numerically reliable method to evaluate the free energy of SARS-CoV-2 binding to other proteins, which may stimulate the development of the therapeutics against the COVID-19 disease in real applications.

ACE2 contributes to the maintenance of mouse epithelial barrier function.

BACKGROUND: The whole world was hit hard by the coronavirus disease-19 (COVID-19). Given that angiotensin I converting enzyme 2 (ACE2) is the viral entry molecule, understanding ACE2 has become a major focus of current COVID-19 research. ACE2 is highly expressed in the gut, but its role has not been fully understood and thus COVID-19 treatments intending to downregulate ACE2 level may cause untoward side effects. Gaining insight into the functions of ACE2 in gut homeostasis therefore merits closer examination, and is beneficial to find potential therapeutic alternatives for COVID-19. METHODS: We took advantage of Ace2 knockout out mice and isolated intestinal organoids to examine the role of ACE2 in intestinal stemness. Inflammatory bowel disease (IBD) mouse model was established by 4% dextran sodium sulfate. LGR5 and KI67 levels were quantitated to reflect the virtue of intestinal stem cells (ISCs). FITC-dextran 4 (FD-4) assay was used to assess intestinal barrier function. RESULTS: Western blotting identified the expression of ACE2 in colon, which was consistent with the results of immunofluorescence and RT-PCR. Moreover, Ace2-/- organoids showed decreased LRG5 and KI67 levels, and elevated calcium concentration. Furthermore, the permeability of ace2-/- organoids was markedly increased compared with ace2+/+ organoids. Collectively, ace2-/- mice were more susceptible than ace2+/+ mice to IBD, including earlier bloody stool, undermined intestinal architecture and more pronounced weight loss. CONCLUSIONS: Our data reveal that ACE2 contributes to the proliferation of intestinal stem cells and hence orchestrates the mucosal homeostasis.

Perioperative management of patients with suspected or confirmed COVID-19: review and recommendations for perioperative management from a retrospective cohort study.

BACKGROUND: Current guidelines for perioperative management of coronavirus disease 19 (COVID-19) are mainly based on extrapolated evidence or expert opinion. We aimed to systematically investigate how COVID-19 affects perioperative management and clinical outcomes, to develop evidence-based guidelines. METHODS: First, we conducted a rapid literature review in EMBASE, MEDLINE, PubMed, Scopus, and Web of Science (January 1 to July 1, 2020), using a predefined protocol. Second, we performed a retrospective cohort analysis of 166 women undergoing Caesarean section at Tongji Hospital, Wuhan during the COVID-19 pandemic. Demographic, imaging, laboratory, and clinical data were obtained from electronic medical records. RESULTS: The review identified 26 studies, mainly case reports/series. One large cohort reported greater mortality in elective surgery patients diagnosed after, rather than before surgery. Higher 30 day mortality was associated with emergency surgery, major surgery, poorer preoperative condition and surgery for malignancy. Regional anaesthesia was favoured in most studies and personal protective equipment (PPE) was generally used by healthcare workers (HCWs), but its use was poorly described for patients. In the retrospective cohort study, duration of surgery, oxygen therapy and hospital stay were longer in suspected or confirmed patients than negative patients, but there were no differences in neonatal outcomes. None of the 262 participating HCWs was infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) when using level 3 PPE perioperatively. CONCLUSIONS: When COVID-19 is suspected, testing should be considered before non-urgent surgery. Until further evidence is available, HCWs should use level 3 PPE perioperatively for suspected or confirmed patients, but research is needed on its timing and specifications. Further research must examine longer-term outcomes. CLINICAL TRIAL REGISTRATION: CRD42020182891 (PROSPERO).