ABSTRACT
During natural disasters or accidents, an emergency logistics network aims to ensure the distribution of relief supplies to victims in time and efficiently. When the coronavirus disease 2019 (COVID-19) emerged, the government closed the outbreak areas to control the risk of transmission. The closed areas were divided into high-risk and middle-/low-risk areas, and travel restrictions were enforced in the different risk areas. The distribution of daily essential supplies to residents in the closed areas became a major challenge for the government. This study introduces a new variant of the vehicle routing problem with travel restrictions in closed areas called the two-echelon emergency vehicle routing problem with time window assignment (2E-EVRPTWA). 2E-EVRPTWA involves transporting goods from distribution centers (DCs) to satellites in high-risk areas in the first echelon and delivering goods from DCs or satellites to customers in the second echelon. Vehicle sharing and time window assignment (TWA) strategies are applied to optimize the transportation resource configuration and improve the operational efficiency of the emergency logistics network. A tri-objective mathematical model for 2E-EVRPTWA is also constructed to minimize the total operating cost, total delivery time, and number of vehicles. A multi-objective adaptive large neighborhood search with split algorithm (MOALNS-SA) is proposed to obtain the Pareto optimal solution for 2E-EVRPTWA. The split algorithm (SA) calculates the objective values associated with each solution and assigns multiple trips to shared vehicles. A non-dominated sorting strategy is used to retain the optimal labels obtained with the SA algorithm and evaluate the quality of the multi-objective solution. The TWA strategy embedded in MOALNS-SA assigns appropriate candidate time windows to customers. The proposed MOALNS-SA produces results that are comparable with the CPLEX solver and those of the self-learning non-dominated sorting genetic algorithm-II, multi-objective ant colony algorithm, and multi-objective particle swarm optimization algorithm for 2E-EVRPTWA. A real-world COVID-19 case study from Chongqing City, China, is performed to test the performance of the proposed model and algorithm. This study helps the government and logistics enterprises design an efficient, collaborative, emergency logistics network, and promote the healthy and sustainable development of cities.
ABSTRACT
During natural disasters or accidents, an emergency logistics network aims to ensure the distribution of relief supplies to victims in time and efficiently. When the coronavirus disease 2019 (COVID-19) emerged, the government closed the outbreak areas to control the risk of transmission. The closed areas were divided into high-risk and middle-/low-risk areas, and travel restrictions were enforced in the different risk areas. The distribution of daily essential supplies to residents in the closed areas became a major challenge for the government. This study introduces a new variant of the vehicle routing problem with travel restrictions in closed areas called the two-echelon emergency vehicle routing problem with time window assignment (2E-EVRPTWA). 2E-EVRPTWA involves transporting goods from distribution centers (DCs) to satellites in high-risk areas in the first echelon and delivering goods from DCs or satellites to customers in the second echelon. Vehicle sharing and time window assignment (TWA) strategies are applied to optimize the transportation resource configuration and improve the operational efficiency of the emergency logistics network. A tri-objective mathematical model for 2E-EVRPTWA is also constructed to minimize the total operating cost, total delivery time, and number of vehicles. A multi-objective adaptive large neighborhood search with split algorithm (MOALNS-SA) is proposed to obtain the Pareto optimal solution for 2E-EVRPTWA. The split algorithm (SA) calculates the objective values associated with each solution and assigns multiple trips to shared vehicles. A non-dominated sorting strategy is used to retain the optimal labels obtained with the SA algorithm and evaluate the quality of the multi-objective solution. The TWA strategy embedded in MOALNS-SA assigns appropriate candidate time windows to customers. The proposed MOALNS-SA produces results that are comparable with the CPLEX solver and those of the self-learning non-dominated sorting genetic algorithm-II, multi-objective ant colony algorithm, and multi-objective particle swarm optimization algorithm for 2E-EVRPTWA. A real-world COVID-19 case study from Chongqing City, China, is performed to test the performance of the proposed model and algorithm. This study helps the government and logistics enterprises design an efficient, collaborative, emergency logistics network, and promote the healthy and sustainable development of cities.
ABSTRACT
SARS-CoV-2 variants often include surface mutations in the Spike protein that are important for viruses to recognize host receptors and evade antibody neutralization. The Spike protein also has mutations in the interior of the protein likely to affect the Spike protein S1 - S2 subunit's separation propensity, the most important of which is the D614G mutation. Remarkably, the Omicron variant contains a large number of internal mutations at the S2: S1 interface, which have not been investigated yet. In this study, we examined the effects of such interfacial mutations on the S2: S1 and subunit domain interactions and on the subunit's dissociation process. We found that the interaction with S2 is mainly contributed by the three encapsulation domains, named INT, ED1 and ED2 of S1, which are sandwiched between the S1 RBD and N-terminal NTD domain. We found that D614 is the strongest contributor for the S2: S1 interaction which is greatly weakened by the D614G mutation. Surprisingly, we found that, mutations T547K, H655Y, N764K, N856K, N969K, L981F in the Omicron variant largely enhance the S2: ED1 interaction, partially compensating the loss of S2: ED2 interaction due to the D614G mutation. Lastly, these results, together with biological considerations, allow us to suggest that in addition to the binding strength of between the RBD and ACE2, the stability of the Spike protein and the propensity of Spike protein S2: S1 separation are critical factors which likely exist in a balance for a particular infectivity and pathogenicity of the virus.
ABSTRACT
We use satellite methane observations from the Tropospheric Monitoring Instrument (TROPOMI), for May 2018 to February 2020, to quantify methane emissions from individual oil and natural gas (O/G) basins in the US and Canada using a high-resolution (∼25 km) atmospheric inverse analysis. Our satellite-derived emission estimates show good consistency with in situ field measurements (R=0.96) in 14 O/G basins distributed across the US and Canada. Aggregating our results to the national scale, we obtain O/G-related methane emission estimates of12.6±2.1 Tg a-1 for the US and 2.2±0.6 Tg a-1 for Canada, 80 % and 40 %, respectively, higher than the national inventories reported to the United Nations. About 70 % of the discrepancy in the US Environmental Protection Agency (EPA) inventory can be attributed to five O/G basins, the Permian, Haynesville, Anadarko, Eagle Ford, and Barnett basins, which in total account for 40 % of US emissions. We show more generally that our TROPOMI inversion framework can quantify methane emissions exceeding 0.2–0.5 Tg a-1 from individual O/G basins, thus providing an effective tool for monitoring methane emissions from large O/G basins globally.
ABSTRACT
The cell surface receptor Neuropilin-1 (Nrp1) was recently identified as a host factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. The Spike protein of SARS-CoV-2 is cleaved into two segments, the S1 (residues (res.) 1-685) and the S2 (res. 686-1273) domains by furin protease. Nrp1 predominantly binds to the C-terminal RRAR amino acid motif (res. 682-685) of the S1 domain. In this study, we firstly modeled the association of an Nrp1 protein (consisting of domains a2-b1-b2) with the Spike protein. Next, we studied the separation of S2 from the S1 domain, with and without Nrp1 bound, by utilizing molecular dynamics pulling simulations. During the separation, Nrp1 stabilizes the S1 C-terminal region (res. 640-685) and thereby assists the detachment of S2 N-terminal region (res. 686-700). Without Nrp1 bound, S1 tends to become stretched, whereas the bound Nrp1 stimulates an earlier separation of S2 from the S1 domain. The liberated S2 domain is known to mediate the fusion of virus and host membranes; thus, Nrp1 likely increases virus infectivity by facilitating the S1 and S2 separation. We further analyzed the possible topological structure of the SARS-CoV-2 Spike protein when bound with Nrp1 and angiotensin-converting enzyme 2 (ACE2). Understanding of such an Nrp1-assisted viral infection opens the gate for the generation of protein-protein inhibitors, such as antibodies, which could attenuate the infection mechanism and protect certain cells in a future Nrp1-ACE2 targeted combination therapy.
ABSTRACT
Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.
Subject(s)
Coronavirus Infections , Weight Loss , COVID-19ABSTRACT
Background: The COVID-19 has high transmission and mortality. Previous studies support the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of lung injury. In this study, We aimed to evaluate the CT changes of lung lesions in severe COVID-19 patients treated with umbilical cord mesenchymal stem cells (UC-MSCs) by using AI-assisted quantification method.Methods46 patients with severe COVID-19 from March 5 to April 1, 2020 were selected by single-blind, non-randomized controlled clinical study and divided into three groups: 11 cases in UC-MSCs treatment group 1 (MSC-1, with cells infusion once), 26 cases in UC-MSCs treatment group 2 (MSC-2, with cells infusion twice or three times), and 9 cases in control group with routine treatment. Repeated measure ANOVA was used to compare the effects of treatment factors on chest CT parameters of COVID-19 patients between control and experimental groups, and pairwise comparison using LSD test.FindingsThe differences between the percentage of GGO in total lung or the percentage of total lung infection volume on day 0 and that in day 60 as well as in day 90 were statistically significant among the three groups. The P values were 0.034 and 0.018 respectively. Pairwise comparison results showed that the percentage difference of the whole lung GGO and total lung infection volume in MSC-1 group was smaller than that in control group and MSC-2 group respectively, but there was no statistical difference between control group and MSC-2 group. The distribution characteristics and other CT parameters post-proceeded by AI software were not significantly different among the three groups. There were no serious adverse events related to stem cell infusion in all treated patients.InterpretationUC-MSC infusion is safe for the treatment of severe COVID-19 patients. The absorption of lung lesions at 60 days and 90 days after UC-MSC infusion once was more obvious than that in the control group. AI quantification of lung lesions is more suitable for comparative studies before and after treatment.
Subject(s)
COVID-19 , Lung Injury , Lung DiseasesABSTRACT
Objectives: To analyze follow-up CTs of patients recovering from COVID-19 in Wuhan, focusing on fibrotic change and its relevant risk factors. Methods: From January 13 to February 27, 2020, 166 hospitalized patients meeting our criteria were included. The scores of fibrotic patterns on follow-up CT were evaluated. Patients were designated as group 1 (with CT evidence of fibrotic pattern) and group 2 (without CT evidence of fibrotic pattern). Multivariate logistic regression was performed to explore risk factors for fibrotic change in patients with COVID-19. Results: The follow-up CTs were obtained on 56 days (median, IQR 51-63 days) after symptom onset. Of the 166 patients (mean age, 57 ± 15 years; 69/166 male), 46% (76/166) had CT evidence of fibrotic change and 77% (127/166) were severe or critical cases. Among patients with fibrotic change on CT, 84% (64/76) got a minimal or mild score of fibrosis. The high total score on peak CT, peak eosinophils, erythrocyte sedimentation rate (ESR) and advancing age were related to lung fibrotic change in patients with COVID-19. Conclusion: Forty six percentages of patients (mainly severe or critical cases) with COVID-19 showed fibrotic change on follow-up CT at early recovery phase, while the extent of fibrosis was not large. The advancing age, high total score on peak CT, peak eosinophils and ESR were associated with fibrotic change depicted by CT in patients recovering from COVID-19. An extended follow up by CT imaging and pulmonary function testing is necessary to fully assess the sequela of COVID-19.
ABSTRACT
Objective@#To establish a colloidal gold technique assay for the rapid detection of immunoglobulin(Ig) M and IgG antibodies against 2019 novel coronavirus (2019-nCoV) and to evaluate its clinical performance.@*Methods@#A total of 278 patients who were treated at Wuhan Hankou Hospital and the People's Hospital of Honghu from February 12, 2020 to February 20, 2020 were collected. According to the diagnostic criteria, 89 patients were confirmed with 2019-nCoV nucleic acid positive diagnosis, and 189 were 2019-nCoV nucleic acid-negative suspected patients. A total of 273 medical examiners from Nanfang Hospital, Southern Medical University from 2015 to 2018 were selected as controls. The serum samples of patients were collected. 2019-nCoV nucleic proteins were obtained from prokaryotic expression vectors. Indirect IgM and IgG colloidal gold techniques were established by using recombinant N protein. 2019-nCoV nucleic acid detection by reverse transcription-polymerase chain reaction (RT-PCR) was used as control. Serum specimens were tested for 2019-nCoV IgM and IgG. The specificity and sensitivity of colloidal gold assay were analyzed.@*Results@#The sensitivity and specificity of IgM detection reagents were 78.7% and 98.2%, respectively, those of IgG detection reagents were 73.0% and 99.3%, respectively, and those of IgM combined with IgG detection were 87.6% and 98.2%, respectively. For suspected patients with negative 2019-nCoV nucleic acid, the positive rates of IgM and IgG were 59.8% (113/189) and 52.9% (100/189), respectively, and the positive rate of IgM combined with IgG detection was 66.1% (125/189).@*Conclusion@#This reagent of 2019-nCoV antibodies detection (colloidal gold technique) fulfills the requirement for clinical application with high specificity and sensitivity, which can be served as a supplementary detection method for 2019-nCoV nucleic acid detection by RT-PCR.