Viral infection dynamics with immune chemokines and CTL mobility modulated by the infected cell density.

We study a viral infection model incorporating both cell-to-cell infection and immune chemokines. Based on experimental results in the literature, we make a standing assumption that the cytotoxic T lymphocytes (CTL) will move toward the location with more infected cells, while the diffusion rate of CTL is a decreasing function of the density of infected cells. We first establish the global existence and ultimate boundedness of the solution via a priori energy estimates. We then define the basic reproduction number of viral infection R 0 and prove (by the uniform persistence theory, Lyapunov function technique and LaSalle invariance principle) that the infection-free steady state E 0 is globally asymptotically stable if R 0 < 1 . When R 0 > 1 , then E 0 becomes unstable, and another basic reproduction number of CTL response R 1 becomes the dynamic threshold in the sense that if R 1 < 1 , then the CTL-inactivated steady state E 1 is globally asymptotically stable; and if R 1 > 1 , then the immune response is uniform persistent and, under an additional technical condition the CTL-activated steady state E 2 is globally asymptotically stable. To establish the global stability results, we need to prove point dissipativity, obtain uniform persistence, construct suitable Lyapunov functions, and apply the LaSalle invariance principle.

Randomness accelerates the dynamic clearing process of the COVID-19 outbreaks in China.

During the implementation of strong non-pharmaceutical interventions (NPIs), more than one hundred COVID-19 outbreaks induced by different strains in China were dynamically cleared in about 40 days, which presented the characteristics of small scale clustered outbreaks with low peak levels. To address how did randomness affect the dynamic clearing process, we derived an iterative stochastic difference equation for the number of newly reported cases based on the classical stochastic SIR model and calculate the stochastic control reproduction number (SCRN). Further, by employing the Bayesian technique, the change points of SCRNs have been estimated, which is an important prerequisite for determining the lengths of the exponential growth and decline phases. To reveal the influence of randomness on the dynamic zeroing process, we calculated the explicit expression of the mean first passage time (MFPT) during the decreasing phase using the relevant theory of first passage time (FPT), and the main results indicate that random noise can accelerate the dynamic zeroing process. This demonstrates that powerful NPI measures can rapidly reduce the number of infected people during the exponential decline phase, and enhanced randomness is conducive to dynamic zeroing, i.e. the greater the random noise, the shorter the average clearing time is. To confirm this, we chose 26 COVID-19 outbreaks in various provinces in China and fitted the data by estimating the parameters and change points. We then calculated the MFPTs, which were consistent with the actual duration of dynamic zeroing interventions.

Modeling the fear effect in the predator-prey dynamics with an age structure in the predators.

We incorporate the fear effect and the maturation period of predators into a diffusive predator-prey model. Local and global asymptotic stability for constant steady states as well as uniform persistence of the solution are obtained. Under some conditions, we also exclude the existence of spatially nonhomogeneous steady states and the steady state bifurcation bifurcating from the positive constant steady state. Hopf bifurcation analysis is carried out by using the maturation period of predators as a bifurcation parameter, and we show that global Hopf branches are bounded. Finally, we conduct numerical simulations to explore interesting spatial-temporal patterns.

The importance of quarantine: modelling the COVID-19 testing process.

We incorporate the disease state and testing state into the formulation of a COVID-19 epidemic model. For this model, the basic reproduction number is identified and its dependence on model parameters related to the testing process and isolation efficacy is discussed. The relations between the basic reproduction number, the final epidemic and peak sizes, and the model parameters are further explored numerically. We find that fast test reporting does not always benefit the control of the COVID-19 epidemic if good quarantine while awaiting test results is implemented. Moreover, the final epidemic and peak sizes do not always increase along with the basic reproduction number. Under some circumstances, lowering the basic reproduction number increases the final epidemic and peak sizes. Our findings suggest that properly implementing isolation for individuals who are waiting for their testing results would lower the basic reproduction number as well as the final epidemic and peak sizes.

Viral infection dynamics with mitosis, intracellular delays and immune response.

In this paper, we propose a delayed viral infection model with mitosis of uninfected target cells, two infection modes (virus-to-cell transmission and cell-to-cell transmission), and immune response. The model involves intracellular delays during the processes of viral infection, viral production, and CTLs recruitment. We verify that the threshold dynamics are determined by the basic reproduction number $ R_0 $ for infection and the basic reproduction number $ R_{IM} $ for immune response. The model dynamics become very rich when $ R_{IM} > 1 $. In this case, we use the CTLs recruitment delay $ \tau_3 $ as the bifurcation parameter to obtain stability switches on the positive equilibrium and global Hopf bifurcation diagrams for the model system. This allows us to show that $ \tau_3 $ can lead to multiple stability switches, the coexistence of multiple stable periodic solutions, and even chaos. A brief simulation of two-parameter bifurcation analysis indicates that both the CTLs recruitment delay $ \tau_3 $ and the mitosis rate $ r $ have a strong impact on the viral dynamics, but they do behave differently.

Viral dynamics with immune responses: effects of distributed delays and Filippov antiretroviral therapy.

In this paper, we propose a general viral infection model to incorporate two infection modes (virus-to-cell mode and cell-to-cell mode), the CTL immune response, and the distributed intracellular delays during the processes of viral infection, viral production, and CTLs recruitment. We investigate the existence, the uniqueness, and the global stability of three equilibria: infection-free equilibrium [Formula: see text], immune-inactivated equilibrium [Formula: see text] and immune-activated equilibrium [Formula: see text], respectively. We prove that the viral dynamics are determined by two threshold parameters: the basic reproduction number for infection [Formula: see text] and the basic reproduction number for immune response [Formula: see text]. We also numerically explore the viral dynamics beyond stability. We use bifurcation diagrams to show that increasing the delay in CTL immune cell recruitment can induce a switch in viral load from a stable constant level to sustained oscillations, and then back to a stable equilibrium. We also compare the contributions of the two infection modes to the total infection level and identify the key parameters that would affect the percentages of virus-to-cell infection and cell-to-cell infection. Finally, we explore how Filippov control can be applied in antiretroviral therapy to reduce the viral loads.

Threshold dynamics of a nonlocal and delayed cholera model in a spatially heterogeneous environment.

A nonlocal and delayed cholera model with two transmission mechanisms in a spatially heterogeneous environment is derived. We introduce two basic reproduction numbers, one is for the bacterium in the environment and the other is for the cholera disease in the host population. If the basic reproduction number for the cholera bacterium in the environment is strictly less than one and the basic reproduction number of infection is no more than one, we prove globally asymptotically stability of the infection-free steady state. Otherwise, the infection will persist and there exists at least one endemic steady state. For the special homogeneous case, the endemic steady state is actually unique and globally asymptotically stable. Under some conditions, the basic reproduction number of infection is strictly decreasing with respect to the diffusion coefficients of cholera bacteria and infectious hosts. When these conditions are violated, numerical simulation suggests that spatial diffusion may not only spread the infection from high-risk region to low-risk region, but also increase the infection level in high-risk region.

Joint impacts of media, vaccination and treatment on an epidemic Filippov model with application to COVID-19.

A non-smooth SIR Filippov system is proposed to investigate the impacts of three control strategies (media coverage, vaccination and treatment) on the spread of an infectious disease. We synthetically consider both the number of infected population and its changing rate as the switching condition to implement the curing measures. By using the properties of the Lambert W function, we convert the proposed switching condition to a threshold value related to the susceptible population. The classical epidemic model involving media coverage, linear functions describing injecting vaccine and treatment strategies is examined when the susceptible population exceeds the threshold value. In addition, we consider another SIR model accompanied with the vaccination and treatment strategies represented by saturation functions when the susceptible population is smaller than the threshold value. The dynamics of these two subsystems and the sliding domain are discussed in detail. Four types of local sliding bifurcation are investigated, including boundary focus, boundary node, boundary saddle and boundary saddle-node bifurcations. In the meantime, the global bifurcation involving the appearance of limit cycles is examined, including touching bifurcation, homoclinic bifurcation to the pseudo-saddle and crossing bifurcation. Furthermore, the influence of some key parameters related to the three treatment strategies is explored. We also validate our model by the epidemic data sets of A/H1N1 and COVID-19, which can be employed to reveal the effects of media report and existing strategy related to the control of emerging infectious diseases on the variations of confirmed cases.

Efficient antimony removal by self-assembled core-shell nanocomposite of Co3O4@rGO and the analysis of its adsorption mechanism.

Co3O4@rGO were facilely prepared by template free self-assemble in this study. The morphology of Co3O4@rGO was actiniaria-like core-shell structural nanocomposites. The formation mechanism of Co3O4@rGO core-shell nanocomposite was discussed according to its significant time-dependent morphology evolution course. To evaluate the application potential of Co3O4@rGO, its adsorption performance toward highly toxic antimony ions were studied. The Co3O4@rGO nanocomposite exhibit high anti-interference ability and high adsorption ability. The maximum adsorption capacities towards Sb(III) and Sb(V) are 151.04 and 165.51 mg/g, respectively. River water samples containing antimony violating the limit were used to evaluate the practical application of Co3O4@rGO, and high performance was achieved. The EU and China limits for antimony in drinking water can be met by using mesoporous Co3O4@rGO treating the actual river water samples with original antimony concentration lower than 50 µg/L. Adsorption isotherm, adsorption kinetics, pH and co-existing ions effects were also studied in details. The results indicate that mesoporous Co3O4@rGO is an excellent adsorbent for antimony removal. Mesoporous Co3O4@rGO nanocomposite is a potential candidate for antimony removal from waste water.

Resonance of Periodic Combination Antiviral Therapy and Intracellular Delays in Virus Model.

There is a substantial interest in detailed models of viral infection and antiviral drug kinetics in order to optimize the treatment against viruses such as HIV. In this paper, we study within-viral dynamics under general intracellular distributed delays and periodic combination antiviral therapy. The basic reproduction number [Formula: see text] is established as a global threshold determining extinction versus persistence, and spectral methods are utilized for analytical and numerical computations of [Formula: see text]. We derive the critical maturation delay for virus and optimal phase difference between sinusoidally varying drug efficacies under various intracellular delays. Furthermore, numerical simulations are conducted utilizing realistic pharmacokinetics and gamma-distributed viral production delays for HIV. Our results demonstrate that the relative timing of the key viral replication cycle steps and periodic antiviral treatment schedule involving distinct drugs all can interact to critically affect the overall viral dynamics.

Synthesis of (ZrO2-Al2O3)/GO nanocomposite by sonochemical method and the mechanism analysis of its high defluoridation.

A nanocomposite of (ZrO2-Al2O3)/GO was successfully synthesized by a simple sonochemical method in this study. A special 3D network was formed in (ZrO2-Al2O3)/GO, which produced a large surface area and good distribution of metal oxide nanoparticles. The as-synthesized (ZrO2-Al2O3)/GO exhibits a maximum fluoride adsorption capacity of 62.2 mg/g, and an adsorption ability of 13.80 mg/g when the F- equilibrium concentration is 1 mg/L, both of which are higher than most previously reported defluoridation adsorbents, indicating that it is among the top adsorbents. Large amounts of drinking water contaminated by F- can be treated by (ZrO2-Al2O3)/GO to meet the WHO limit, indicating the high potential for practical application of the adsorbent. Based on the experimental analysis, the origin of the high defluoridation performance and the adsorption mechanism were discussed in detail. Due to the simple preparation, easy operation and high performance, the adsorbent and the related sonochemical method are considered to be significant for developing highly effective adsorbents.

Mitochondrial DNA variations in tongue squamous cell carcinoma.

Tongue squamous cell carcinoma (TSCC) is the most common type of oral carcinoma. Mitochondrial DNA (mtDNA) is a circular DNA molecule of 16,569 bp, which functionally encompasses a regulatory non-coding region (D-loop) and 37 encoding genes that correspond to 13 subunits of respiratory chain complexes (I, III, IV and V), 22 transfer RNAs and 2 ribosomal (r)RNAs. Recently, mtDNA has been implicated as a mutation hotspot in various tumors. However, to our knowledge mtDNA alteration in TSCC has not been investigated to date. In the present study, the mitochondrial genomes of tongue carcinoma, adjacent non-cancerous tissue and peripheral blood samples from 8 patients with TSCC were sequenced and aligned with the revised Cambridge Reference Sequence. Overall, only one synonymous mutation, which mapped to the NADH:ubiquinone oxidoreductase core subunit 5 gene, was observed in the tongue carcinoma sample from a single patient. A further 21 polymorphisms were identified, including six in the non-coding region (D-loop), five in Complex I, three in Complex III, two in Complex IV, two in Complex V and three in rRNA. In addition, mitochondrial microsatellite instability (mtMSI) was detected in 2/8 tongue carcinoma samples, and localized in the D310 region. These variations, particularly the polymorphisms and mtMSI, imply that the mitochondrial genome may be a hotspot of genome alteration in tongue cancer. Further investigation is expected to reveal the role of mtDNA alteration in TSCC development, as well as its clinical implications.

Maternal genetic backgrounds contribute to the genetic susceptibility of tongue cancer patients in Hunan, central of China.

Mitochondrial DNA (mtDNA) mutations played crucial roles on affecting the susceptibility to cancer. In this study, to investigate whether mitochondrial DNA mutations contributed to the genetic susceptibility of Chinese tongue cancer patients, mtDNA control regions of 105 Chinese tongue cancer patients were amplified and sequenced, the mutations were recorded by comparing with the revised Cambridge Reference Sequence (rCRS), which were attributed to certain mtDNA haplogroups based on the specific variations motif of each patients. The Miao Chinese group (a Chinese ethnic minority) from surrounding region has no essential difference with tongue cancer group, which was taken as the matched control group with principal component analysis by taking the haplogroups frequency of 105 tongue cancer individuals and 354 healthy individuals of eight groups from the similar geographic regions as input factors. This was supported by the smallest genetic distance between tongue cancer and Miao_2 groups. Further, the statistical analysis based on mtDNA variations of hypervariable sequence I (HVSI) indicated that 13 variations including 16,124, 16,148, 16,182C, 16,183C, 16,227, 16,266A, 16,249, 16,272, 16,291, 16,327, 16,335, 16,497, and 16,519 have significant differences between tongue cancer group and matched control group. Comparison of mtDNA haplogroups between tongue cancer and control groups indicated that mtDNA haplogroups C, F2*, and M10 have significant differences. It's worth noting that 16,327 and 16,291 was the defining variation of haplogroups C and F2*, respectively. Our results suggested that mitochondrial DNA may play a crucial role for the maternal genetic susceptibility of tongue cancer patients from Hunan, central of China.

c.464A>G variation in the GJB2 gene is detected in a Han Chinese family.

We report two heterozygous carriers of c.464A>G variation in the GJB2 gene in a Chinese pedigree. The proband with hearing loss most likely inherited the c.464A>G variation from his mother who also carries heterozygous c.79G>A variation and has normal hearing. The pathological significance of c.464A>G variation remains to be determined.

Global analysis on a class of multi-group SEIR model with latency and relapse.

In this paper, we investigate the global dynamics of a multi-group SEIR epidemic model, allowing heterogeneity of the host population, delay in latency and delay due to relapse distribution for the human population. Our results indicate that when certain restrictions on nonlinear growth rate and incidence are fulfilled, the basic reproduction number R0 plays the key role of a global threshold parameter in the sense that the long-time behaviors of the model depend only on R0. The proofs of the main results utilize the persistence theory in dynamical systems, Lyapunov functionals guided by graph-theoretical approach.

Delay induced stability switch, multitype bistability and chaos in an intraguild predation model.

In many predator-prey models, delay has a destabilizing effect and induces oscillations; while in many competition models, delay does not induce oscillations. By analyzing a rather simple delayed intraguild predation model, which combines both the predator-prey relation and competition, we show that delay in intraguild predation models promotes very complex dynamics. The delay can induce stability switches exhibiting a destabilizing role as well as a stabilizing role. It is shown that three types of bistability are possible: one stable equilibrium coexists with another stable equilibrium (node-node bistability); one stable equilibrium coexists with a stable periodic solution (node-cycle bistability); one stable periodic solution coexists with another stable periodic solution (cycle-cycle bistability). Numerical simulations suggest that delay can also induce chaos in intraguild predation models.

Sustained and transient oscillations and chaos induced by delayed antiviral immune response in an immunosuppressive infection model.

Sustained and transient oscillations are frequently observed in clinical data for immune responses in viral infections such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. To account for these oscillations, we incorporate the time lag needed for the expansion of immune cells into an immunosuppressive infection model. It is shown that the delayed antiviral immune response can induce sustained periodic oscillations, transient oscillations and even sustained aperiodic oscillations (chaos). Both local and global Hopf bifurcation theorems are applied to show the existence of periodic solutions, which are illustrated by bifurcation diagrams and numerical simulations. Two types of bistability are shown to be possible: (i) a stable equilibrium can coexist with another stable equilibrium, and (ii) a stable equilibrium can coexist with a stable periodic solution.

Mitochondrial common deletion, a potential biomarker for cancer occurrence, is selected against in cancer background: a meta-analysis of 38 studies.

Mitochondrial dysfunction has been long proposed to play a major role in tumorigenesis. Mitochondrial DNA (mtDNA) mutations, especially the mtDNA 4,977 bp deletion has been found in patients of various types of cancer. In order to comprehend the mtDNA 4,977 bp deletion status in various cancer types, we performed a meta-analysis composed of 33 publications, in which a total of 1613 cancer cases, 1516 adjacent normals and 638 healthy controls were included. When all studies were pooled, we found that cancerous tissue carried a lower mtDNA 4,977 bp deletion frequency than adjacent non-cancerous tissue (OR = 0.43, 95% CI = 0.20-0.92, P = 0.03 for heterogeneity test, I(2) = 91.5%) among various types of cancer. In the stratified analysis by cancer type the deletion frequency was even lower in tumor tissue than in adjacent normal tissue of breast cancer (OR = 0.19, 95% CI = 0.06-0.61, P = 0.005 for heterogeneity test, I(2)= 82.7%). Interestingly, this observation became more significant in the stratified studies with larger sample sizes (OR = 0.70, 95% CI = 0.58-0.86, P = 0.0005 for heterogeneity test, I(2) = 95.1%). Furthermore, when compared with the normal tissue from the matched healthy controls, increased deletion frequencies were observed in both adjacent non-cancerous tissue (OR = 3.02, 95% CI = 2.13-4.28, P<0.00001 for heterogeneity test, I(2)= 53.7%), and cancerous tissue (OR = 1.36, 95% CI = 1.04-1.77, P = 0.02 for heterogeneity test, I(2)= 83.5%). This meta-analysis suggests that the mtDNA 4,977 bp deletion is often found in cancerous tissue and thus has the potential to be a biomarker for cancer occurrence in the tissue, but at the same time being selected against in various types of carcinoma tissues. Larger and better-designed studies are still warranted to confirm these findings.

Joint effects of mitosis and intracellular delay on viral dynamics: two-parameter bifurcation analysis.

To understand joint effects of logistic growth in target cells and intracellular delay on viral dynamics in vivo, we carry out two-parameter bifurcation analysis of an in-host model that describes infections of many viruses including HIV-I, HBV and HTLV-I. The bifurcation parameters are the mitosis rate r of the target cells and an intracellular delay τ in the incidence of viral infection. We describe the stability region of the chronic-infection equilibrium E* in the two-dimensional (r, τ) parameter space, as well as the global Hopf bifurcation curves as each of τ and r varies. Our analysis shows that, while both τ and r can destabilize E* and cause Hopf bifurcations, they do behave differently. The intracellular delay τ can cause Hopf bifurcations only when r is positive and sufficiently large, while r can cause Hopf bifurcations even when τ = 0. Intracellular delay τ can cause stability switches in E* while r does not.

Novel Cu (II) magnetic ion imprinted materials prepared by surface imprinted technique combined with a sol-gel process.

A novel Cu (II) magnetic ion-imprinted polymer (MIIP) was synthesized by surface imprinting technique combined with a sol-gel process. The adsorbent of Cu (II)-MIIP shows higher capacity and selectivity than that of magnetic non-imprinted polymers (MNIP). Adsorption capacities of Cu (II)-MIIP and MNIP are 24.2 and 5.2mg/g for Cu (II) ions, respectively. The selectivity coefficients of the Cu (II)-MIIP for Cu (II)/Zn (II) and Cu (II)/Ni (II) are 91.84 and 133.92, respectively. Kinetics studies show that the adsorption process obeys pseudo-second-order rate mechanism with an initial adsorption rate of 132.48 for Cu (II)-MIIP and 2.41mgg(-1)min(-1) for MNIP. In addition, no obvious decrease was observed after up to five adsorption cycles, indicating that the Cu (II)-MIIP is of high stability.