Rapid Generation of Pulmonary Organoids from Induced Pluripotent Stem Cells by Co-Culturing Endodermal and Mesodermal Progenitors for Pulmonary Disease Modelling.

Differentiation of induced pluripotent stem cells to a range of target cell types is ubiquitous in monolayer culture. To further improve the phenotype of the cells produced, 3D organoid culture is becoming increasingly prevalent. Mature organoids typically require the involvement of cells from multiple germ layers. The aim of this study was to produce pulmonary organoids from defined endodermal and mesodermal progenitors. Endodermal and mesodermal progenitors were differentiated from iPSCs and then combined in 3D Matrigel hydrogels and differentiated for a further 14 days to produce pulmonary organoids. The organoids expressed a range of pulmonary cell markers such as SPA, SPB, SPC, AQP5 and T1α. Furthermore, the organoids expressed ACE2 capable of binding SARS-CoV-2 spike proteins, demonstrating the physiological relevance of the organoids produced. This study presented a rapid production of pulmonary organoids using a multi-germ-layer approach that could be used for studying respiratory-related human conditions.

Myocardin Reverses Hypoxia-Inducible Factor-1α Mediated Phenotypic Modulation of Corpus Cavernosum Smooth Muscle Cells in Hypoxia Induced by Cobalt Chloride.

PURPOSE: We aimed to investigate the mechanism of phenotypic transformation of corporal cavernosum smooth muscle cells (CCSMCs) under hypoxic conditions in vitro. MATERIALS AND METHODS: In this study, a hypoxia model was established using cobalt chloride (CoCl2). CCSMCs were treated with different concentrations of CoCl2 for varying time periods, and cell viability was assessed. Hypoxia-inducible factor-1α (HIF-1α), myocardin (Myocd) and phenotypic markers were detected in the CCSMCs. We also transfected the CCSMCs with si-HIF-1α and Ad-Myocd and evaluated the effects on phenotypic modulation of CCSMCs and the relationship between HIF-1α and Myocd was evaluated. RESULTS: CoCl2 inhibited the viability of CCSMCs in a dose- and time-dependent manner, and treatment with 300 µM CoCl2 for 48 hours were the optimal conditions for establishing the hypoxia model. The results showed increased expression levels of HIF-1α and osteopontin and decreased Myocd, alpha-smooth muscle actin, and calponin levels in CCSMCs under hypoxia. HIF-1α knockdown reversed hypoxia-induced phenotypic transformation with elevated Myocd expression. Overexpression of Myocd also reversed the effect of hypoxia on the phenotypic switch, but did not affect HIF-1α expression. CONCLUSIONS: Our findings showed that HIF-1α was involved in the effect of hypoxia induced by CoCl2 on CCSMC phenotypic modulation, and Myocd overexpression could inhibit this process. Thus, Myocd might be a potential therapeutic target for erectile dysfunction under hypoxia or HIF-1α activation.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

Separating Daily 1 km PM2.5 Inorganic Chemical Composition in China since 2000 via Deep Learning Integrating Ground, Satellite, and Model Data.

Fine particulate matter (PM2.5) chemical composition has strong and diverse impacts on the planetary environment, climate, and health. These effects are still not well understood due to limited surface observations and uncertainties in chemical model simulations. We developed a four-dimensional spatiotemporal deep forest (4D-STDF) model to estimate daily PM2.5 chemical composition at a spatial resolution of 1 km in China since 2000 by integrating measurements of PM2.5 species from a high-density observation network, satellite PM2.5 retrievals, atmospheric reanalyses, and model simulations. Cross-validation results illustrate the reliability of sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-) estimates, with high coefficients of determination (CV-R2) with ground-based observations of 0.74, 0.75, 0.71, and 0.66, and average root-mean-square errors (RMSE) of 6.0, 6.6, 4.3, and 2.3 µg/m3, respectively. The three components of secondary inorganic aerosols (SIAs) account for 21% (SO42-), 20% (NO3-), and 14% (NH4+) of the total PM2.5 mass in eastern China; we observed significant reductions in the mass of inorganic components by 40-43% between 2013 and 2020, slowing down since 2018. Comparatively, the ratio of SIA to PM2.5 increased by 7% across eastern China except in Beijing and nearby areas, accelerating in recent years. SO42- has been the dominant SIA component in eastern China, although it was surpassed by NO3- in some areas, e.g., Beijing-Tianjin-Hebei region since 2016. SIA, accounting for nearly half (∼46%) of the PM2.5 mass, drove the explosive formation of winter haze episodes in the North China Plain. A sharp decline in SIA concentrations and an increase in SIA-to-PM2.5 ratios during the COVID-19 lockdown were also revealed, reflecting the enhanced atmospheric oxidation capacity and formation of secondary particles.

Characteristics of unintentional childhood injury during COVID-19: a single-center comparative study.

Background: There are many articles related to child injuries during the coronavirus disease of 2019 (COVID-19) in other countries, but only few studies in this field in China. This study analyzes the clinical characteristics of unintentional childhood injury during the pandemic, to provide reference for the prevention of unintentional childhood injury in the context of pandemic. Methods: A comparative study was performed on the medical data of 2,497 children with unintentional injury who were hospitalized at Chengdu Women's and Children's Central Hospital between 1 January, 2018 and 31 May, 2021. The study period was divided into 2 periods, before the pandemic (1 January, 2018 to 31 May, 2019), during the pandemic (1 January, 2020 to 31 May, 2021). The number of unintentional childhood injuries and age distribution before and during the pandemic were compared. Group differences were examined using Mann-Whitney U for continuous variables and Chi-squared or Kruskal-Wallis tests for categorical variables. Results: There were significant differences in age, accident location, hospitalization days, and medical expenses before and during the pandemic (P<0.05). During the pandemic, the number of children's unintentional injuries increased by 34.24% (1,066 vs. 1,431, P=0.000), and the significantly increased types of unintentional injuries included foreign bodies, falls, crush injuries, and sharp injuries. During the pandemic, the highest proportion of unintentional injury to children was foreign bodies, whereas the proportion of falls was the highest before the pandemic. During the pandemic, the number of foreign body injuries in toddler was significantly higher than before the pandemic (P=0.001), but the number of falls, crush injuries, and sharp injuries in preschooler was significantly higher (P<0.05). Conclusions: In the circumstance of the COVID-19, the number of foreign bodies, falls, crush injuries, and sharp injuries, in children increased significantly. It is necessary to strengthen the prevention of foreign bodies in toddler, and falls, crush injuries, and sharp injuries in preschooler.

Effect of anxiety and depression on self-reported adverse reactions to COVID-19 vaccine: a cross-sectional study in Shanghai, China.

BACKGROUND: The association of anxiety and depression with adverse reactions after receipt of coronavirus disease 2019 (COVID-19) vaccine is not clear among the general population. This study aims to evaluate the effect of anxiety and depression on self-reported adverse reactions to COVID-19 vaccine. METHODS: The cross-sectional study was conducted during April-July 2021. Participants completing the two doses of vaccine were included in this study. Sociodemographic information, anxiety and depression levels and adverse reactions after the first dose of vaccine for all participants were collected. The anxiety and depression levels were assessed by the Seven-item Generalized Anxiety Disorder Scale and the Nine-item Patient Health Questionnaire Scale, respectively. The multivariate logistic regression analysis was used to examine the association between anxiety and depression and adverse reactions. RESULTS: A total of 2161 participants were enrolled in this study. The prevalence of anxiety and depression was 13% (95% confidence interval (CI), 11.3-14.2%) and 15% (95%CI, 13.6-16.7%), respectively. Of the 2161 participants, 1607 (74%; 95% CI, 73-76%) reported at least one adverse reaction after the first dose of the vaccine. Pain at the injection site (55%) and fatigue and headache (53% and 18%, respectively) were the most commonly reported local and systemic adverse reactions, respectively. Participants with anxiety or depression or both were more likely to report local and systemic adverse reactions (P < 0.05). CONCLUSION: The results suggest that anxiety and depression increase the risk of self-reported adverse reactions to COVID-19 vaccine. Consequently, appropriate psychological interventions before vaccination will help to reduce or alleviate symptoms of vaccination.

Enhancing the student learning experience: Co-teaching biochemistry and clinical sciences within the dental curriculum.

Basic knowledge of biochemistry underpins oral and dental care. Undergraduate dental students do not always engage well with basic science teaching due to not appreciating its clinical relevance. Co-teaching provides one approach to overcome students' disengagement and involves two lecturers, with complementary expertise, presenting the curriculum together. This study investigated student experiences and engagement using co-teaching to integrate biochemistry with clinical sciences in the students' second-year dental curriculum. Two successive second year dental student cohorts were co-taught. Content was delivered by a biochemist and an oral biologist, either online (during the 2020 COVID lockdown) or in-person (2021). Each cohort was surveyed at the end of the teaching module using an online questionnaire containing both interval scale and free-text questions. Responses were received from 39 (42%) and 64 (85%) of students in 2020 and 2021, respectively. Students from both cohorts preferred the co-teaching approach with a mean of 8.74 on a 10-point interval scale. In 2020 and 2021, 77% and 76% of participants, respectively, preferred a combined biochemistry and clinical dentistry delivery, either in-person (37%), via Zoom (19%) or via video recording (14%). Thematic analysis of responses revealed students experienced enhanced engagement when co-taught and they attributed this to integration of the curriculum making the content more relevant and stimulating. Students preferred co-teaching to individual subjects being taught by a single teacher. Co-teaching established the relevance of theoretical biochemistry to clinical dental sciences and enhanced the students' learning experience.

Urban resilience under the COVID-19 pandemic: A quantitative assessment framework based on system dynamics.

The COVID-19 pandemic, which lasted for three years, has had a great impact on the public health system, society and economy of cities, revealing the insufficiency of urban resilience under large-scale public health events (PHEs). Given that a city is a networked and multidimensional system with complex interactions, it is helpful to improve urban resilience under PHEs based on system thinking. Therefore, this paper proposes a dynamic and systematic urban resilience framework that incorporates four subsystems (governance, infrastructures, socioeconomy and energy-material flows). The composite index, system dynamics and epidemic simulation model are integrated into the framework to show the nonlinear relationships in the urban system and reflect the changing trend of urban resilience under PHEs. Then, urban resilience under different epidemic scenarios and response policy scenarios is calculated and discussed to provide some suggestions for decision-makers when faced with the trade-off between the control of PHEs and the maintenance of city operation. The paper concludes that control policies could be adjusted according to the characteristics of PHEs; strict control policies under a severe epidemic could lead to a significant decrease in urban resilience, while a more flexible control strategy can be adopted under a mild epidemic scenario to ensure the normal operation of urban functions. Moreover, the critical functions and impact factors of each subsystem are identified.

Factors Influencing Retention among Regional, Rural and Remote Undergraduate Nursing Students in Australia: A Systematic Review of Current Research Evidence.

BACKGROUND: This systematic review aimed to explore the factors influencing retention among regional, rural, and remote undergraduate nursing students who were enrolled in Australian universities. METHODS: Mixed-methods systematic review. A+ Education, CINAHL, Education Resources Information Center (ERIC), Education Research Complete, JBI EBP database, Journals@Ovid, Medline, PsycINFO, PubMed, and Web of Science were systematically searched from September 2017 to September 2022 to identify eligible English-language studies. The methodological quality of the included studies was critically assessed using the Joanna Briggs Institute's critical appraisal tools. Descriptive analysis with a convergent segregated approach was conducted to synthesize and integrate the results from the included studies. RESULTS: Two quantitative and four qualitative studies were included in this systematic review. Both the quantitative and qualitative findings demonstrated that additional academic and personal support was essential for improving retention among undergraduate nursing students from regional, rural, and remote areas in Australia. The qualitative synthesis also highlighted many internal (e.g., personal qualities, stress, ability to engage with classes and institutions, time management, lack of confidence, cultural well-being, and Indigenous identity) and external factors (e.g., technical difficulties, casual tutors, different competing demands, study facilities, and financial and logistical barriers) that influenced retention among undergraduate nursing students from regional, rural, and remote areas in Australia. CONCLUSIONS: This systematic review demonstrates that identifying potentially modifiable factors could be the focus of retention support programs for undergraduate nursing students. The findings of this systematic review provide a direction for the development of retention support strategies and programs for undergraduate nursing students from regional, rural and remote areas in Australia.

Based on network pharmacology and bioinformatics to analyze the mechanism of action of Astragalus membranaceus in the treatment of vitiligo and COVID-19.

Coronavirus disease 2019 (COVID-19) is spreading rapidly around the world. However, the treatment of vitiligo combined with COVID-19 has not been reported. Astragalus membranaceus (AM) has a therapeutic effect on patients with vitiligo and COVID-19. This study aims to discover its possible therapeutic mechanisms and provide potential drug targets. Using the Chinese Medicine System Pharmacological Database (TCMSP), GEO database and Genecards websites and other databases, AM target, vitiligo disease target, and COVID-19 related gene set were established. Then find the crossover genes by taking the intersection. Then use GO, KEGG enrichment analysis, and PPI network to discover its underlying mechanism. Finally, by importing drugs, active ingredients, crossover genes, and enriched signal pathways into Cytoscape software, a "drug-active ingredient-target signal pathway-" network is constructed. TCMSP screened and obtained 33 active ingredients including baicalein (MOL002714), NEOBAICALEIN (MOL002934), Skullcapflavone II (MOL002927), and wogonin (MOL000173), which acted on 448 potential targets. 1166 differentially expressed genes for vitiligo were screened by GEO. CIVID-19 related genes were screened by Genecards. Then by taking the intersection, a total of 10 crossover genes (PTGS2, CDK1, STAT1, BCL2L1, SCARB1, HIF1A, NAE1, PLA2G4A, HSP90AA1, and HSP90B1) were obtained. KEGG analysis found that it was mainly enriched in signaling pathways such as IL-17 signaling pathway, Th17 cell differentiation, Necroptosis, NOD-like receptor signaling pathway. Five core targets (PTGS2, STAT1, BCL2L1, HIF1A, and HSP90AA1) were obtained by analyzing the PPI network. The network of "active ingredients-crossover genes" was constructed by Cytoscape, and the 5 main active ingredients acting on the 5 core crossover genes acacetin, wogonin, baicalein, bis2S)-2-ethylhexyl) benzene-1,2-dicarboxylate and 5,2'-Dihydroxy-6,7,8-trimethoxyflavone. The core crossover genes obtained by PPI and the core crossover genes obtained by the "active ingredient-crossover gene" network are intersected to obtain the three most important core genes (PTGS2, STAT1, HSP90AA1). AM may act on PTGS2, STAT1, HSP90AA1, etc. through active components such as acacetin, wogonin, baicalein, bis2S)-2-ethylhexyl) benzene-1,2-dicarboxylate and 5,2'-Dihydroxy-6,7,8-trimethoxyflavone to activate IL-17 signaling pathway, Th17 cell differentiation, Necroptosis, NOD-like receptor signaling pathway, Kaposi sarcoma-associated herpesvirus infection, and VEGF signaling pathway and other signaling pathways to achieve the effect of treating vitiligo and COVID-19.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study.

Background: Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods: We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings: 264 patients (mean age, 70.35 years; 122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27; 95% CI -2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group; ARD, -0.62; 95% CI -2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39; serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation: Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS-CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding: National Natural Science Foundation of China (grant number: 82172152, 81873944).

The association of self-control, self-efficacy, and demographic characteristics with home-based E-learning behavior in nursing and midwifery undergraduates: A cross-sectional study under the COVID-19 epidemic.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, nursing and midwifery undergraduate students' time spent in home isolation and being engaged in home-based e-learning was extended. Limited research has been conducted on home-based e-learning behavior during home isolation, and the relationships between individual factors, such as self-control, self-efficacy, and other demographic characteristics, and home-based e-learning behavior are unclear. OBJECTIVES: This study aimed to explore the associations between self-control, self-efficacy, and demographic information with home-based e-learning behavior among nursing and midwifery undergraduates during the COVID-19 pandemic. DESIGN AND METHODS: A cross-sectional study was employed, and an online survey was conducted with 3733 nursing and midwifery undergraduates across seven provinces and cities in mainland China. Data were collected using the Brief Self-control Scale, General Self-efficacy Scale, Undergraduate Home-based E-learning Behavior Questionnaire, and Demographic Information Questionnaire. A multiple linear regression analysis using the stepwise method was conducted to identify predictors of home-based e-learning behavior. RESULTS: Undergraduates achieved an overall mean score of 26.02 (SD = 4.20) for home-based e-learning behavior and an overall mean score of 42.54 (SD = 6.22) and 27.59 (SD = 3.89) for self-control and self-efficacy, respectively. Better self-control (ß = 0.250, P < 0.001), higher self-efficacy (ß = 0.169, P < 0.001), universities being located in non-Hainan provinces (ß = 0.249, P < 0.001), being a sophomore or freshman (ß = -0.255, P < 0.001), and good perceived health status (ß = -0.044, P = 0.003) were identified as the predictors of better home-based e-learning behavior among nursing and midwifery undergraduates. CONCLUSION: Self-control, self-efficacy, and demographic characteristics including the province of the university, grade level, and personal perceived health status were associated with home-based e-learning behavior. Universities should help nursing and midwifery undergraduates improve self-control and enhance self-efficacy while taking measures to decrease the impact caused by demographic characteristic differences.

Efficacy and safety of Paxlovid in severe adult patients with SARS-Cov-2 infection: a multicenter randomized controlled study

Background Nirmatrelvir plus ritonavir (Paxlovid) reduced the risk of hospitalization or death by 89% in high-risk, ambulatory adults with COVID-19. We aimed at studying the efficacy and safety of Paxlovid in hospitalized adult patients with SARS-Cov-2 (Omicron BA.2.2 variant) infection and severe comorbidities. Methods We conducted an open-label, multicenter, randomized controlled trial in which hospitalized adult patients with severe comorbidities were eligible and assigned in a 1:1 ratio to receive either 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 h for 5 days with standard treatment or only standard treatment. All-cause mortality on day 28, the duration of SARS-CoV-2 RNA clearance, and safety were evaluated. Findings 264 patients (mean age, 70.35 years;122 [46.21%] female) who met the criteria were enrolled at 5 sites in Shanghai from April 10 to May 19 in 2022. After randomization, a total of 132 patients were assigned to receive Paxlovid treatment plus standard treatment, and 132 patients were assigned to receive only standard treatment. The overall 28-day mortality was 4.92%, 8 patients died in the standard treatment group and 5 died in the Paxlovid plus standard treatment group. There was no significant difference in mortality from any cause at 28 days between the Paxlovid plus standard treatment group and the standard treatment group (absolute risk difference [ARD], 2.27;95% CI −2.94 to 7.49, P = 0.39). There was no significant difference in the duration of SARS-CoV-2 RNA clearance among the two groups (mean days, 10 in Paxlovid plus standard treatment group and 10.50 in the standard treatment group;ARD, −0.62;95% CI −2.29 to 1.05, P = 0.42). The incidence of adverse events that occurred during the treatment period was similar in the two groups (any adverse event, 10.61% with Paxlovid plus standard treatment vs. 7.58% with the standard, P = 0.39;serious adverse events, 4.55% vs. 3.788%, P = 0.76). Interpretation Paxlovid showed no significant reduction in the risk of all-cause mortality on day 28 and the duration of SARS–CoV-2 RNA clearance in hospitalized adult COVID-19 patients with severe comorbidities. Funding 10.13039/501100001809National Natural Science Foundation of China (grant number: 82172152, 81873944).

Irradiation accelerates SARS-CoV-2 infection by enhancing sphingolipid metabolism.

Cancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS-CoV-2 using S pseudovirions and probed the underlying mechanism via RNA-seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS-CoV-2 invasion. Inhibition of lipid raft formation with methyl-ß-cyclodextrin (MßCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS-CoV-2 S pseudovirion infection in A549 cell tumour-bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation-induced SARS-CoV-2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID-19.

γ-Core Guided Antibiotic Design Based on Human Enteric Defensin 5.

An increase in the number of infections caused by resistant bacteria worldwide necessitates the development of alternatives to antibiotics. Human defensin (HD) 5 is an innate immune peptide with broad-spectrum antibacterial activity, but its complicated structure makes its preparation difficult. Herein, we truncated the HD5 structure by extracting the highly conserved γ-core motif. A structure-activity study showed that this motif was ineffective in killing bacteria in the absence of specific spatial conformation. Notably, after the introduction of two intramolecular disulfide bonds, its antibacterial activity was markedly improved. Glu and Ser residues were then replaced with Arg to create the derivative RC18, which exhibited stronger potency than HD5, particularly against methicillin-resistant S. aureus (MRSA). Mechanistically, RC18 bound to lipid A and lipoteichoic acid at higher affinities than HD5. Furthermore, RC18 was more efficient than HD5 in penetrating the bacterial membranes. Molecular dynamics simulation revealed that five Arg residues, Arg1, Arg7, Arg9, Arg15, and Arg18, mediated most of the polar interactions of RC18 with the phospholipid head groups during membrane penetration. In vivo experiments indicated that RC18 decreased MRSA colonization and dramatically improved the survival of infected mice, thus demonstrating that RC18 is a promising drug candidate to treat MRSA infections.

Future Education of Cartography and GIS: What Is Next?

Cartography and maps support the continuous rising of the awareness of the power of spatial data, which further lays a foundation for the popularity of various location based services and applications in society. Cartography and Geographic Information System education has been a core activity in the cartographic academic community for knowledge creation and transfer in higher education institutions. Maps in primary and high schools play a unique role across disciplines to build the spatial thinking capacities of young generations. Over years educators train students via lectures and lab works into which digital technologies are gradually incorporated. The COVID-19 pandemic has been fast forwarding our pace to employ digital technologies in online teaching and learning. Teachers are passively or proactively adapted to conduct their teaching online and redesign their lectures and assessments of students' performance. On another side, students are getting used to online learning even more quickly with various digital devices in an interactive and collective way. It creates opportunities for cartographic GIS educators to build a body of knowledge for cartography which can be used to build open source educational resources systematically. Further flexible curriculum can be designed and implemented for professional and continuous education and training at various levels. Future education of cartography and GIS can improve map literacy and make a sustainable education.

Decline of onset-to-diagnosis interval and its impacts on clinical outcome of COVID-19 in China: a nation-wide observational study.

BACKGROUND: To quantitatively assess the impact of the onset-to-diagnosis interval (ODI) on severity and death for coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study was conducted based on the data on COVID-19 cases of China over the age of 40 years reported through China's National Notifiable Infectious Disease Surveillance System from February 5, 2020 to October 8, 2020. The impacts of ODI on severe rate (SR) and case fatality rate (CFR) were evaluated at individual and population levels, which was further disaggregated by sex, age and geographic origin. RESULTS: As the rapid decline of ODI from around 40 days in early January to < 3 days in early March, both CFR and SR of COVID-19 largely dropped below 5% in China. After adjusting for age, sex, and region, an effect of ODI on SR was observed with the highest OR of 2.95 (95% CI 2.37‒3.66) at Day 10-11 and attributable fraction (AF) of 29.1% (95% CI 22.2‒36.1%) at Day 8-9. However, little effect of ODI on CFR was observed. Moreover, discrepancy of effect magnitude was found, showing a greater effect from ODI on SR among patients of male sex, younger age, and those cases in Wuhan. CONCLUSION: The ODI was significantly associated with the severity of COVID-19, highlighting the importance of timely diagnosis, especially for patients who were confirmed to gain increased benefit from early diagnosis to some extent.