On the solution of the Human Immunodeficiency Virus(HIV)infection model using spectral collocation method

In this research work,we study the Human Immunodeficiency Virus(HIV)infection on helper T cells governed by a mathematical model consisting of a system of three first-order nonlinear differential equations.The objective of the analysis is to present an approximate mathematical solution to the model that gives the count of the numbers of uninfected and infected helper T cells and the number of free virus particles present at a given instant of time.The system of nonlinear ODEs is converted into a system of nonlinear algebraic equations using spectral collocation method with three different basis functions such as Chebyshev,Legendre and Jacobi polynomials.Some factors such as the production of helper T cells and infection of these cells play a vital role in infected and uninfected cell counts.Detailed error analysis is done to compare our results with the existing methods.It is shown that the spectral collocation method is a very reliable,efficient and robust method of solution compared to many other solution procedures available in the literature.All these results are presented in the form of tables and figures.

Stability and Hopf bifurcation of a delayed virus infection model with latently infected cells and Beddington-DeAngelis incidence

In this paper,the dynamical behaviors for a five-dimensional virus infection model with Latently Infected Cells and Beddington-DeAngelis incidence are investigated.In the model,four delays which denote the latently infected delay,the intracel-lular delay,virus production period and CTL response delay are considered.We define the basic reproductive number and the CTL immune reproductive number.By using Lyapunov functionals,LaSalle's invariance principle and linearization method,the threshold conditions on the stability of each equilibrium are established.It is proved that when the basic reproductive number is less than or equal to unity,the infection-free equilibrium is globally asy mptot ically stable;when the CTL immune repro-ductive number is less than or equal to unity and the basic reproductive number is greater than unity,the immune free infection equilibrium is globally asymptotically stable;when the CTL immune reproductive number is greater than unity and immune response delay is equal to zero,the immune infection equilibrium is globally asymptotically stable.The results show that immune response delay may destabilize the steady state of infection and lead to Hopf bifurcation.The existence of the Hopf bifurcation is discussed by using immune response delay as a bifurcation parameter.Numerical simulations are carried out to justify the analytical results.

Numerical Solutions of a Novel Designed Prevention Class in the HIV Nonlinear Model

The presented research aims to design a new prevention class(P)in the HIV nonlinear system,i.e.,the HIPV model.Then numerical treatment of the newly formulated HIPV model is portrayed handled by using the strength of stochastic procedure based numerical computing schemes exploiting the artificial neural networks(ANNs)modeling legacy together with the optimization competence of the hybrid of global and local search schemes via genetic algorithms(GAs)and active-set approach(ASA),i.e.,GA-ASA.The optimization performances through GA-ASA are accessed by presenting an error-based fitness function designed for all the classes of the HIPV model and its corresponding initial conditions represented with nonlinear systems of ODEs.To check the exactness of the proposed stochastic scheme,the comparison of the obtained results and Adams numerical results is performed.For the convergence measures,the learning curves are presented based on the different contact rate values.Moreover,the statistical performances through different operators indicate the stability and reliability of the proposed stochastic scheme to solve the novel designed HIPV model.

NONINVASIVE OPTICAL IMAGING OF STAPHYLOCOCCUS AUREUS INFECTION IN VIVO USING AN ANTIMICROBIAL PEPTIDE FRAGMENT BASED NEAR-INFRARED FLUORESCENT PROBES

The diagnosis of bacterial infections remains a major challenge in medicine.Optical imaging of bacterial infection in living animals is usually conducted with genetic reporters such as lightemitting encymes or fluorescent proteins.However,there are many circumstances where genetic reporters are not applicable,and there is an urgent need for exogenous synthetic probes that can selectively target bacteria.Optical imaging of bacteria in vivo is much less developed than methods such as ndioimaging and MRI.Furthermore near infrared(NIR)dyes with emision wavelengths in the region of 650-900 rm can propagate through two or more centimeters of tissue and may enable deeper tisue imaging if sensitive detection techniques are employed.Here we constructed an antimicrobial peptide fragment UBI29-41-based near infrared fuorescent imaging probe.The probe is composed of UBI2941 conjugated to a near infraured dye ICG Der-02.UBI29-41 is a cationic antimicrobial peptide that targets the anionic surfaces of bacterial cells.The probe allows detection of Staphylococcus aureus infection(5×10^(7)cells)in a mouse local infection model using whole animal nearinfrared fuorescence imaging.Furthermore,we demonstrate that the UBI29-41-based imaging probe can selectively accumulate within bacteria.The significantly higher accumulation in bacterial infection suggests that UBI29-41-based imaging probe may be a promising imaging agent to detect bacterial infections.

Cryptotanshinone inhibits cytotoxin-associated gene A-associated development of gastric cancer and mucosal erosions

BACKGROUND Approximately 90%of new cases of noncardiac gastric cancer(GC)are related to Helicobacter pylori(H.pylori),and cytotoxin-associated gene A(CagA)is one of the main pathogenic factors.Recent studies have shown that the pharmacological effects of cryptotanshinone(CTS)can be used to treat a variety of tumors.However,the effects of CTS on H.pylori,especially CagA+strain-induced gastric mucosal lesions,on the development of GC is unknown.AIM To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells,and determine if CagA+H.pylori strains causes pathological changes in the gastric mucosa of mice.METHODS The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8(CCK-8)assay,and the abnormal growth,migration and invasion caused by CagA were detected by CCK-8 and transwell assays.After transfection with pSR-HA-CagA and treatment with CTS,proliferation and metastasis were evaluated by CCK-8 and transwell assays,respectively,and the expression of Src homology 2(SH2)domain–containing phosphatase 2(SHP2)and phosphorylated SHP2(p-SHP2)was detected using western blotting in AGS cells.The enzymelinked immunosorbent assay was used to determine the immunoglobulin G(IgG)level against CagA in patient serum.Mice were divided into four groups and administered H.pylori strains(CagA+or CagA-)and CTS(or PBS)intragastrically,and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains.Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney.RESULTS CTS inhibited the growth of GC cells in dose-and time-dependent manners.Overexpression of CagA promoted the growth,migration,and invasion of GC cells.Importantly,we demonstrated that CTS significantly inhibited the CagAinduced abnormal proliferation,migration,and invasion of GC cells.Moreover,the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients.Additionally,CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells.CTS suppressed CagA+H.pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA-H.pylori strain group.CONCLUSION CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro,and CagA+H.pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.

Establishment of a model of Mycoplasma hyopneumoniae infection using Bama miniature pigs

Mycoplasma hyopneumoniae(M.hyopneumoniae),is the primary aetiological agent of enzootic pneumonia leading to chronic respiratory disease prevalent worldwide.Conventional pigs are the only animals used for pathogenicity studies and vaccine evaluations of M.hyopneumoniae.Considering that the challenge animals have better genetic stability and a smaller body size to operate with,an alternative experimental animal model of M.hyopneumoniae infection with Bama miniature pigs was established.Nine seven-week-old snatch-farrowed,porcine colostrum-deprived(SF-pCD)Bama miniature pigs and nine conventional pigs were randomly divided into two infected groups(Bama miniatureinfected(BI)and conventional-infected groups(CI),BI and CI,n=6)and two control groups(Bama miniature control(BC)and conventional control(CC)groups,BC and CC,n=3).Every piglet was tracheally inoculated with 5×10^(8) CCU/mL containing 10%suspension of a stock of frozen lung homogenate from SF-pCD pigs infected with virulent strain JS or sterilized KM2 medium.Typical lung lesions appeared in all infected pigs after necropsy,and the mean gross lung lesions was 17.3 and 13.7 in groups of BI and CI.Serum IgG and nasal sIgA antibody titres were increased significantly.Cilia shedding and mucus staining increased greatly in JS-infected bronchi.Obvious reddish gross lesions and M.hyopneumoniae antigen were detected,especially apparently observed in group of BI.Moreover,DNA copies of M.hyopneumoniae from bronchoalveolar lavage fluid(BALF)of each JS-infected piglet reached more than 10^(8),and M.hyopneumoniae could be re-isolated from each infected BALF.These results indicate that Bama miniature pigs could be used as an alternative and more maneuverable experimental infection model for M.hyopneumoniae and display typical clinical and pathological features consistent with those in conventional pigs.

LCH:A local clustering H-index centrality measure for identifying and ranking influential nodes in complex networks

Identifying influential nodes in complex networks is one of the most significant and challenging issues,which may contribute to optimizing the network structure,controlling the process of epidemic spreading and accelerating information diffusion.The node importance ranking measures based on global information are not suitable for large-scale networks due to their high computational complexity.Moreover,they do not take into account the impact of network topology evolution over time,resulting in limitations in some applications.Based on local information of networks,a local clustering H-index(LCH)centrality measure is proposed,which considers neighborhood topology,the quantity and quality of neighbor nodes simultaneously.The proposed measure only needs the information of first-order and second-order neighbor nodes of networks,thus it has nearly linear time complexity and can be applicable to large-scale networks.In order to test the proposed measure,we adopt the susceptible-infected-recovered(SIR)and susceptible-infected(SI)models to simulate the spreading process.A series of experimental results on eight real-world networks illustrate that the proposed LCH can identify and rank influential nodes more accurately than several classical and state-of-the-art measures.

Improvement of the software for modeling the dynamics of epidemics and developing a user-friendly interface

The challenges humanity is facing due to the Covid-19 pandemic require timely and accurate forecasting of the dynamics of various epidemics to minimize the negative consequences for public health and the economy.One can use a variety of well-known and new mathematical models,taking into account a huge number of factors.However,complex models contain a large number of unknown parameters,the values of which must be determined using a limited number of observations,e.g.,the daily datasets for the accumulated number of cases.Successful experience in modeling the COVID-19 pandemic has shown that it is possible to apply the simplest SIR model,which contains 4 unknown parameters.Application of the original algo-rithm of the model parameter identification for the first waves of the COVID-19 pandemic in China,South Korea,Austria,Italy,Germany,France,Spain has shown its high accuracy in pre-dicting their duration and number of diseases.To simulate different epidemic waves and take into account the incompleteness of statistical data,the generalized SIR model and algorithms for determining the values of its parameters were proposed.The interference of the previous waves,changes in testing levels,quarantine or social behavior require constant monitoring of the epidemic dynamics and performing SIR simulations as often as possible with the use of a user-friendly interface.Such tool will allow predicting the dynamics of any epidemic using the data on the number of diseases over a limited period(e.g.,14 days).It will be possible to predict the daily number of new cases for the country as a whole or for its separate region,to estimate the number of carriers of the infection and the probability of facing such a carrier,as well as to estimate the number of deaths.Results of three SIR simulations of the COVID-19 epidemic wave in Japan in the summer of 2022 are presented and discussed.The predicted accumulated and daily numbers of cases agree with the results of observations,especially for the simulation based on the datasets corresponding to the period from July 3 to July 16,2022.A user-friendly interface also has to ensure an opportunity to compare the epidemic dynamics in different countries/regions and in different years in order to estimate the impact of vaccination levels,quarantine restrictions,social behavior,etc.on the numbers of new infections,death,and mortality rates.As example,the comparison of the COVID-19 pandemic dynamics in Japan in the summer of 2020,2021 and 2022 is presented.The high level of vaccinations achieved in the summer of 2022 did not save Japan from a powerful pandemic wave.The daily numbers of cases were about ten times higher than in the corresponding period of 2021.Nevertheless,the death per case ratio in 2022 was much lower than in 2020.

The threshold for a stochastic within-host CHIKV virus model with saturated incidence rate

This paper deals with stochastic Chikungunya(CHIKV)virus model along with saturated incidence rate.We show that there exists a unique global positive solution and also we obtain the conditions for the disease to be extinct.We also discuss about the existence of a unique ergodic stationary distribution of the model,through a suitable Lyapunov function.The stationary distribution validates the occurrence of disease;through that,we find the threshold value for prevail and disappear of disease within host.With the help of numerical simulations,we validate the stochastic reproduction number Rq as stated in our theoretical findings.

Some models with repulsion effect on superinfecting viruses by infected cells

In this paper,we study some models with repulsion effect on superinfecting viruses by infected cells{■T/■t=DT△T(x,t)-■(TФ(T,I)■I)+h(x)-dTT(x,t)-β(x)T(x,t)V(x,t),■I/■T=DT△I+β(x)T(x,t)V(x,t)-dII(xt,),■I/■T=■(Dv(I)■V)+γ(x)I(x,t)-dvV(x,t),where T(x,t),I(x,t)and V(x,t)are the density of uninfected cells,infected cells and viruses at time t at location x,respectively.The functions h(x),β(x)andγ(x)are assumed to be positive,continuous and bounded.h(x)denotes the production rate of uninfected cells.The infection rate isβ(x)and the functionγ(x)is the production rate of free viruses.Andβ(x)T(x,t)V(x,t)is the rate of transfer from uninfected cells to infected cells.The positive constants dT,dI and dV denote the death rate of uninfected cells,infected cells and viruses,respectively.The stability of the infection-free equilibrium solution and infection equilibrium solution is discussed.It is shown that if the basic reproduction number R0≤1 then the chemotaxis has no effect,that is,the infection-free constant solution is stable.For the system with chemotactic sensitivityФ(T,I)=1-T,if R0>1,then the infection constant solution will be unstable under some conditions.