Delay induced stability switch in a mathematical model of CD8 T-cell response to SARS-CoV-2 mediated by receptor ACE2.

The pathogen SARS-CoV-2 binds to the receptor angiotensin-converting enzyme 2 (ACE2) of the target cells and then replicates itself through the host, eventually releasing free virus particles. After infection, the CD8 T-cell response is triggered and appears to play a critical role in the defense against virus infections. Infected cells and their activated CD8 T-cells can cause tissue damage. Here, we established a mathematical model of within-host SARS-CoV-2 infection that incorporates the receptor ACE2, the CD8 T-cell response, and the damaged tissues. According to this model, we can get the basic reproduction number R0 and the immune reproduction number R1. We provide the theoretical proof for the stability of the disease-free equilibrium, immune-inactivated equilibrium, and immune-activated equilibrium. Finally, our numerical simulations show that the time delay in CD8 T-cell production can induce complex dynamics such as stability switching. These results provide insights into the mechanisms of SARS-CoV-2 infection and may help in the development of effective drugs against COVID-19.

A COVID-19 Infection Model Considering the Factors of Environmental Vectors and Re-Positives and Its Application to Data Fitting in Japan and Italy.

COVID-19, which broke out globally in 2019, is an infectious disease caused by a novel strain of coronavirus, and its spread is highly contagious and concealed. Environmental vectors play an important role in viral infection and transmission, which brings new difficulties and challenges to disease prevention and control. In this paper, a type of differential equation model is constructed according to the spreading functions and characteristics of exposed individuals and environmental vectors during the virus infection process. In the proposed model, five compartments were considered, namely, susceptible individuals, exposed individuals, infected individuals, recovered individuals, and environmental vectors (contaminated with free virus particles). In particular, the re-positive factor was taken into account (i.e., recovered individuals who have lost sufficient immune protection may still return to the exposed class). With the basic reproduction number R0 of the model, the global stability of the disease-free equilibrium and uniform persistence of the model were completely analyzed. Furthermore, sufficient conditions for the global stability of the endemic equilibrium of the model were also given. Finally, the effective predictability of the model was tested by fitting COVID-19 data from Japan and Italy.

Global asymptotic stability of a delay differential equation model for SARS-CoV-2 virus infection mediated by ACE2 receptor protein.

The COVID-19 pandemic has brought a serious threat to human life safety worldwide. SARS-CoV-2 virus mainly binds to the target cell surface receptor ACE2 (Angiotensin-converting enzyme 2 ) through the S protein expressed on the surface of the virus, resulting in infection of target cells. During this infection process, the target cell ACE2 receptor plays a very important mediating role. In this paper, a delay differential equation model containing the mediated effect of target cell receptor is established according to the mechanism of SARS-CoV-2 virus invasion of target cells, and the global stability of the infection-free equilibrium and the infected equilibrium of the model is obtained by using the basic reproduction number  ℛ 0  and constructing the appropriate Lyapunov functional. The expression of the basic reproduction number  ℛ 0  intuitively gives the dependence on the expression ratio of the target cell surface ACE2 receptor, which is helpful for the understanding of the mechanism of SARS-CoV-2 virus infection.

Shigellosis seasonality and transmission characteristics in different areas of China: A modelling study.

Objective: In China, the burden of shigellosis is unevenly distributed, notably across various ages and geographical areas. Shigellosis temporal trends appear to be seasonal. We should clarify seasonal warnings and regional transmission patterns. Method: This study adopted a Logistic model to assess the seasonality and a dynamics model to compare the transmission in different areas. The next-generation matrix was used to calculate the effective reproduction number (R eff) to quantify the transmissibility. Results: In China, the rate of shigellosis fell from 35.12 cases per 100,000 people in 2005 to 7.85 cases per 100,000 people in 2017, peaking in June and August. After simulation by the Logistic model, the 'peak time' is mainly concentrated from mid-June to mid-July. China's 'early warning time' is primarily focused on from April to May. We predict the 'peak time' of shigellosis is the 6.30th month and the 'early warning time' is 3.87th month in 2021. According to the dynamics model results, the water/food transfer pathway has been mostly blocked off. The transmissibility of different regions varies greatly, such as the mean R eff of Longde County (3.76) is higher than Xiamen City (3.15), higher than Chuxiong City (2.52), and higher than Yichang City (1.70). Conclusion: The 'early warning time' for shigellosis in China is from April to May every year, and it may continue to advance in the future, such as the early warning time in 2021 is in mid-March. Furthermore, we should focus on preventing and controlling the person-to-person route of shigellosis and stratified deploy prevention and control measures according to the regional transmission.

An Optimized Method for Adipose Stromal Vascular Fraction Isolation and its Application in Fat Grafting.

BACKGROUND: The stromal vascular fraction (SVF) derived from adipose tissue contains heterogeneous cell populations and has enormous potential for clinical therapy. There are two main methods for SVF isolation: enzymatic isolation and mechanical isolation, both of which have shortcomings. In this study, optimized conditions for the isolation of high-quality SVF were established, and applications in fat grafting were evaluated. METHODS: Adipose tissue was chopped into small pieces and then ground into an erosive shape using a syringe. The pieces were digested with 0.15% type II collagenase for 35 min at 37 °C. After centrifugation, the pellets were resuspended in DMEM and passed through a 100-µm strainer. The filtered cells were analyzed by flow cytometry. The fat graft was enriched with isolated SVF and subcutaneously transplanted into nude mice. Three weeks after transplantation, grafts were isolated, and H&E staining, immunocytochemistry, and western blotting were conducted. RESULTS: The harvested SVF cells reached > 2 × 106/ml of adipose tissue within 90 min of operation. The number of CD34+ ADSCs in our SVF pellets was > 6 × 105/ml of adipose tissue, which has the potential for differentiating into osteoblasts, adipocytes, and chondrocytes. Freshly collected adipose tissue is better for SVF isolation, and isolated SVF should also be kept at 4 °C and used as soon as possible. SVF may promote revascularization after fat grafting. The adipose tissue of an SVF co-transplanted group had an integral structure, clear capillaries, and higher VEGF expression. SVF co-transplantation inhibited adipose cell apoptosis. CONCLUSION: Our study provides an efficient procedure for SVF isolation, its application in fat grafting, and possible underlying mechanisms. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The transmission dynamics of Middle East Respiratory Syndrome coronavirus.

BACKGROUND: In this study, we aimed to quantify the contribution of different transmission routes of the Middle East respiratory syndrome (MERS) and determine its transmissibility. METHODS: Based on the natural history and transmission features of MERS in different countries, a susceptible-exposed-symptomatic-asymptomatic-recovered/death (SEIARD) model and a multi-route dynamic model (MMDM). The SEIARD model and MMDM were adopted to simulate MERS in South Korea and Saudi Arabia, respectively. Data on reported MERS cases in the two countries were obtained from the World Health Organization. Thereafter, the next generation matrix method was employed to derive the equation for the basic reproduction number (R0), and the model fitting procedure was adopted to calculate the R0 values corresponding to these different countries. RESULTS: In South Korea, 'Person-to-Person' transmission was identified as the main mode of MERS transmission in healthcare settings, while in Saudi Arabia, in addition to 'Person-to-Person' transmission, 'Host-to-Host' and 'Host-to-Person' transmission also occurred under certain scenarios, with camels being the main host. Further, the fitting results showed that the SEIARD model and MMDM fitted the data well. The mean R0 value was 8.59 (95% confidence interval [CI]: 0-28.02) for MERS in South Korea, and for MERS in Saudi Arabia, it was 1.15 and 1.02 (95% CI: 0.86-1.44) for the 'Person-to-Person' and 'Camel-to-Camel' transmission routes, respectively. CONCLUSIONS: The SEIARD and MMDM model can be used to simulate the transmission of MERS in different countries. Additionally, in Saudi Arabia, the transmissibility of MERS was almost the same among hosts (camels) and humans.

Analysis of the Static and Dynamic Imbibition Effect of Surfactants and the Relative Mechanism in Low-Permeability Reservoirs.

Establishing an effective displacement system for conventional water flooding development in low-permeability reservoirs is difficult, with generally low liquid and oil production and a worse water flooding effect. Imbibition oil recovery technology has received increasing attention from oil development workers because of its simple operation, low cost, and good oil increase effect. To explore the method and mechanism to further improve the effect of imbibition oil recovery, we study the imbibition and oil recovery effect and its influencing factors in a low-permeability reservoir in the Dagang Oilfield based on evaluation indexes of the adhesion work reduction factor, ratio of capillary force to gravity N B -1, regression analysis of the recovery rate of imbibition, proportional relationship with spontaneous imbibition, and dynamic imbibition effect in crack rocks. Results show that reducing the interfacial tension of the surfactant on the imbibition process has a dual effect. The selection of the surfactant for fractured tight reservoirs should not excessively pursue ultralow interfacial tension, and it should consider the surface wettability environment favorable for imbibition to ensure that a sufficient driving force can be provided. In the initial imbibition stage, the capillary force is large, the velocity of water imbibition in pores is fast, and the oil recovery rate is high; the holding time of the imbibition process is important to imbibition recovery. With the increase in imbibition time, the capillary force weakens, and the imbibition speed decreases to zero. With the increase in injection volume, reservoir pressure, pressure holding time, and imbibition cycles, the oil recovery increases, but the amplification of oil recovery decreases. From the technical and economic viewpoints, the optimal slug size, throughput cycle, and pressure holding time of the target reservoir are recommended as follows: 0.5 PV,three3 rounds, and greater than 96 h, respectively.

Asymptomatic transmission shifts epidemic dynamics.

Asymptomatic transmission of infectious diseases has been recognized recently in several epidemics or pandemics. There is a great need to incorporate asymptomatic transmissions into traditional modeling of infectious diseases and to study how asymptomatic transmissions shift epidemic dynamics. In this work, we propose a compartmental model with asymptomatic transmissions for waterborne infectious diseases. We conduct a detailed analysis and numerical study with shigellosis data. Two parameters, the proportion $p$ of asymptomatic infected individuals and the proportion $k$ of asymptomatic infectious individuals who can asymptomatically transmit diseases, play major rules in the epidemic dynamics. The basic reproduction number $\mathscr{R}_{0}$ is a decreasing function of parameter $p$ when parameter $k$ is smaller than a critical value while $\mathscr{R}_{0}$ is an increasing function of $p$ when $k$ is greater than the critical value. $\mathscr{R}_{0}$ is an increasing function of $k$ for any value of $p$. When $\mathscr{R}_{0}$ passes through 1 as $p$ or $k$ varies, the dynamics of epidemics is shifted. If asymptomatic transmissions are not counted, $\mathscr{R}_{0}$ will be underestimated while the final size may be overestimated or underestimated. Our study provides a theoretical example for investigating other asymptomatic transmissions and useful information for public health measurements in waterborne infectious diseases.

Effects of strain and strain-induced α'-martensite on passive films in AISI 304 austenitic stainless steel.

In this paper, the effects of strain and heat treatment on strain-induced α'-martensite of AISI 304 stainless steel tubes were measured by X-ray diffraction. Moreover, the effects of strain and content of α'-martensite on passivated property on the surface of the material in borate buffer solution were evaluated by electrochemical technique. The results showed that the volume fraction of α'-martensite increased gradually with the increase of tensile strain for as-received and solid solution samples. However, α'-martensite in as-received sample was more than that in the solid solution sample. The electrochemical impedance spectroscopy results showed that the solid solution treatment improved corrosion resistance of the steel, especially for samples with small strain. Moreover, acceptor densities were always higher than donor densities for as-received and solid solution samples. With the increase of strain, the increase tendency of acceptor density was more significant than that of donor density. We also found that the total density of the acceptor and donor almost increased linearly with the increase of α'-martensite. The present results indicated that the increased acceptor density might lead to the decreased corrosion resistance of the steel.