DYNAMICAL BEHAVIOR OF A STOCHASTIC HBV INFECTION MODEL WITH LOGISTIC HEPATOCYTE GROWTH

This paper is concerned with a stochastic HBV infection model with logistic growth. First, by constructing suitable stochastic Lyapunov functions, we establish sufficient conditions for the existence of ergodic stationary distribution of the solution to the HBV infection model. Then we obtain sufficient conditions for extinction of the disease. The stationary distribution shows that the disease can become persistent in vivo.

Global Stability of a Viral Infection Model with Defectively Infected Cells and Latent Age

The authors propose and analyze a viral infection model with defectively infected cells and age of the latently infected cells.The existence of steady states is determined by the basic reproduction number of virus.With the Lyapunov's direct method,they establish a threshold dynamics of the model with the basic reproduction number of virus as the threshold parameter.To achieve it,a novel procedure is proposed.Its novelties are two-folded.On one hand,the coefficients involved in the specific forms of the used Lyapunov functionals for the two feasible steady states are determined by the same set of inequalities.On the other hand,for the infection steady state,a new approach is proposed to check whether the derivative of the Lyapunov functional candidate along solutions is negative(semi-)definite or not.This procedure not only simplifies the analysis but also exhibits the relationship between the two Lyapunov functionals for the two feasible steady states.Moreover,the procedure is expected to be applicable for other similar models.

A Trichophyton Rubrum Infection Model Based on the Reconstructed Human Epidermis - Episkin

Background： Trichophyton rubrum represents the most common infectious fungus responsible for dermatophytosis in human, but the mechanism involved is still not completely understood. An appropriate model constructed to simulate host infection is the prerequisite to study the pathogenesis of dernlatophytosis caused by T.. rubrum. In this study, we intended to develop a new T. rubrum infection model in vitro, using the three-dimensional reconstructed epidermis - EpiSkin, and to pave the way for further investigation of the mechanisms involved in T. rubrum infection. Methods： The reconstructed human epidermis （RHE） was infected by inoculating low-dose （400 conidia） and high-dose （4000 conidia） T. rubrum conidia to optimize the infection dose. During the various periods after infection, the samples were processed for pathological examination and scanning electron microscopy （SEM） observation. Results： The histological analysis of RHE revealed a fully differentiated epidermis with a functional stratum corneum, which was analogous to the normal human epidermis. The results of hematoxylin and eosin staining and the periodic acid-Schiff staining showed that the infection dose of 400 conidia was in accord with the pathological characteristics of host dermatophytosis caused by T. rubrum. SEM observations further exhibited the process of 77 ruhrum infection in an intuitionistic way, Conclusions： We established the T. rubrum infection model on RHE in vitro successfully. It is a promising model fbr further investigation of the mechanisms involved in T. rubrum infection.

Establishment of Multi-Site Infection Model in Zebrafish Larvae for Studying Staphylococcus aureus Infectious Disease

Zebrafish（Danio rerio） is an ideal model for studying the mechanism of infectious disease and the interaction between host and pathogen.As a teleost,zebrafish has developed a complete immune system which is similar to mammals.Moreover,the easy acquirement of large amounts of transparent embryos makes it a good candidate for gene manipulation and drug screening.In a zebrafish infection model,all of the site,timing,and dose of the bacteria microinjection into the embryo are important factors that determine the bacterial infection of host.Here,we established a multi-site infection model in zebrafish larvae of 36 hours post-fertilization（hpf） by micro-injecting wild-type or GFP-expressing Staphylococcus aereus（5.aureus） with gradient burdens into different embryo sites including the pericardial cavity（PC）,eye,the fourth hindbrain ventricle（4V）,yolk circulation valley（YCV）,caudal vein（CV）,yolk body（YB）,and Duct of Cuvier（DC） to resemble human infectious disease.With the combination of GFP-expressing S.aureus and transgenic zebrafish Tg（corola：eGFP;lyz：Dsred） and Tg（lyz：Dsred） lines whose macrophages or neutrophils are fluorescent labeled,we observed the dynamic process of bacterial infection by in vivo multicolored confocal fluorescence imaging.Analyses of zebrafish embryo survival, bacterial proliferation and myeloid cells phagocytosis show that the site- and dose-dependent differences exist in infection of different bacterial entry routes.This work provides a consideration for the future study of pathogenesis and host resistance through selection of multi-site infection model.More interaction mechanisms between pathogenic bacteria virulence factors and the immune responses of zebrafish could be determined through zebrafish multi-site infection model.

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.

Stability analysis for delayed viral infection model with multitarget cells and general incidence rate

In this paper, the sharp threshold properties of a （2n ＋ 1）-dimensional delayed viral infection model are investigated. This model combines with n classes of uninfected tar- get cells, n classes of infected cells and nonlinear incidence rate h（x,v）. Two kinds of distributed time delays are incorporated into the model to describe the time needed for infection of uninfected target cells and virus replication. Under certain conditions, it is shown that the basic reproduction number is a threshold parameter for the existence of the equilibria, uniform persistence, as well as for global stability of the equilibria of the model.

Establishment of a Predictive Diagnostic Model for Acute Mycoplasma Pneumoniae Infection in Elderly Patients with Community-acquired Pneumonia

We established a diagnostic model to predict acute Mycoplasma pneumoniae （M. pneumonia） infection in elderly Community-acquired pneumonia （CAP） patients. We divided 456 patients into acute and non-acute M. pneumoniae infection groups. Binary logistic regression and receiver operating characteristic （ROC） curves were used to establish a predictive model. The following independent factors were identified： age 〉 70 years; serum cTNT level 〉 0.0S ng/mL; lobar consolidation; mediastinal lymphadenopathy; and antibody titer in the acute phase 〉 1：40. The area under the ROC curve of the model was 0.923 and a score of 2 7 score predicted acute M. pneumoniae infection in elderly patients with CAP. The predictive model developed in this study has high diagnostic accuracy for the identification of elderly acute M. pneumoniae infection.

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.

Global Piecewise Analysis of HIV Model with Bi-Infectious Categories under Ordinary Derivative and Non-Singular Operator with Neural Network Approach

This study directs the discussion of HIV disease with a novel kind of complex dynamical generalized and piecewise operator in the sense of classical and Atangana Baleanu(AB)derivatives having arbitrary order.The HIV infection model has a susceptible class,a recovered class,along with a case of infection divided into three sub-different levels or categories and the recovered class.The total time interval is converted into two,which are further investigated for ordinary and fractional order operators of the AB derivative,respectively.The proposed model is tested separately for unique solutions and existence on bi intervals.The numerical solution of the proposed model is treated by the piece-wise numerical iterative scheme of Newtons Polynomial.The proposed method is established for piece-wise derivatives under natural order and non-singular Mittag-Leffler Law.The cross-over or bending characteristics in the dynamical system of HIV are easily examined by the aspect of this research having a memory effect for controlling the said disease.This study uses the neural network(NN)technique to obtain a better set of weights with low residual errors,and the epochs number is considered 1000.The obtained figures represent the approximate solution and absolute error which are tested with NN to train the data accurately.

Viral and cellular determinants involved in hepadnaviral entry

Hepadnaviridae is a family of hepatotropic DNA viruses that is divided into the genera orthohepadnavirus of mammals and avihepadnavirus of birds. All members of this family can cause acute and chronic hepatic infection, which in the case of human hepatitis B virus （HBV） constitutes a major global health problem. Although our knowledge about the molecular biology of these highly liver-specific viruses has profoundly increased in the last two decades, the mechanisms of attachment and productive entrance into the differentiated host hepatocytes are still enigmatic. The difficulties in studying hepadnaviral entry were primarily caused by the lack of easily accessible in vitro infection systems. Thus, for more than twenty years, differentiated primary hepatocytes from the respective species were the only in vitro models for both orthohepadnaviruses （e.g. HBV） and avihepadnaviruses （e.g. duck hepatitis B virus [DHBV]）. Two important discoveries have been made recently regarding HBV： （1） primary hepatoo/tes from tree-shrews; i.e., Tupaia belangeri, can be substituted for primary human hepatocytes, and （2） a human hepatoma cell line （HepaRG） was established that gains susceptibility for HBV infection upon induction of differentiation in vitro. A number of potential HBV receptor candidates have been described in the past, but none of them have been confirmed to function as a receptor. For DHBV and probably all other avian hepadnaviruses, carboxypeptidase D （CPD） has been shown to be indispensable for infection, although the exact role of this molecule is still under debate. While still restricted to the use of primary duck hepatocytes （PDH）, investigations performed with DHBV provided important general concepts on the first steps of hepadnaviral infection. However, with emerging data obtained from the new HBV infection systems, the hope that DHBV utilizes the same mechanism as HBV only partially held true. Nevertheless, both HBV and DHBV in vitro infection systems will help to： （1） functionally dissect the hepadnaviral entry pathways, （2） perform reverse genetics （e.g. test the fitness of escape mutants）, （3） titrate and map neutralizing antibodies, （4） improve current vaccines to combat acute and chronic infections of hepatitis B, and （5） develop entry inhibitors for future clinical applications.

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.

Stability of a CD4^＋ T cell viral infection model with diffusion

This paper is devoted to the study of the stability of a CD4^＋ T cell viral infection model with diffusion. First, we discuss the well-posedness of the model and the existence of endemic equilibrium. Second, by analyzing the roots of the characteristic equation, we establish the local stability of the virus-free equilibrium. Furthermore, by constructing suitable Lyapunov functions, we show that the virus-free equilibrium is globally asymptotically stable if the threshold value R0 ≤1; the endemic equilibrium is globally asymptotically stable if R0 〉 1 and du^＊ - δw^＊ ≥0. Finally, we give an application and numerical simulations to illustrate the main results.

A numerical method for the solutions of the HIV infection model of CD4＋ T-cells

In this paper, the human immunodeficiency virus （HIV） infection model of CD4＋ T-cells is considered. In order to numerically solve the model problem, an operational method is proposed. For that purpose, we construct the operational matrix of integration for bases of Taylor polynomials. Then, by using this matrix operation and approximation by polynomials, the HIV infection problem is transformed into a system of algebraic equations, whose roots are used to determine the approximate solutions. An important feature of the method is that it does not require collocation points. In addition, an error estimation technique is presented. We apply the present method to two numerical examples and compare our results with other methods.

ANALYSIS ON STABILITY OF AN AUTONOMOUS DYNAMICS SYSTEM FOR SARS EPIDEMIC

An extended dynamic model for SARS epidemic was deduced on the basis of the K-M infection model with taking the density constraint of susceptible population and the cure and death rates of patients into consideration. It is shown that the infectionfree equilibrium is the global asymptotic stability under given conditions, and endemic equilibrium is not the asymptotic stability. It comes to the conclusion that the epidemic system is the permanent persistence existence under appropriate conditions.

Bio-inspired computational heuristics to study models of HIV infection of CD4＋ T-cell

In this work, biologically-inspired computing framework is developed for HIV infection of CD4＋ T-cell model using feed-forward artificial neural networks （ANNs）, genetic algorithms （GAs）, sequential quadratic programming （SQP） and hybrid approach based on GA-SQP. The mathematical model for HIV infection of CD4＋ T-cells is represented with the help of initial value problems （IVPs） based on the system of ordinary differential equations （ODEs）. The ANN model for the system is constructed by exploiting its strength of universal approximation. An objective function is developed for the system through unsupervised error using ANNs in the mean square sense. Training with weights of ANNs is carried out with GAs for effective global search supported with SQP for efficient local search. The proposed scheme is evaluated on a number of scenarios for the HIV infection model by taking the different levels for infected cells, natural substitution rates of uninfected cells, and virus particles. Comparisons of the approximate solutions are made with results of Adams numerical solver to establish the correctness of the proposed scheme. Accuracy and convergence of the approach are validated through the results of statistical analysis based on the sufficient large number of independent runs.

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.

Crucial role played by CK8^(+)cells in mediating alveolar injury remodeling for patients with COVID-19

The high risk of SARS-CoV-2 infection and reinfection and the occurrence of post-acute pulmonary sequelae have highlighted the importance of understanding the mechanism underlying lung repair after injury.To address this concern,comparative and systematic analyses of SARS-CoV-2 infection in COVID-19 patients and animals were conducted.In the lungs of nine patients who died of COVID-19 and one recovered from COVID-19 but died of unrelated disease in early 2020,damage-related transient progenitor(DATP)cells expressing CK8 marker proliferated significantly.These CK8^(+)DATP cells were derived from bronchial CK5^(+)basal cells.However,they showed different cell fate toward differentiation into type I alveolar cells in the deceased and convalescent patients,respectively.By using a self-limiting hamster infection model mimicking the dynamic process of lung injury remodeling in mild COVID-19 patients,the accumulation and regression of CK8t cell marker were found to be closely associated with the disease course.Finally,we examined the autopsied lungs of two patients who died of infection by the recent Omicron variant and found that they only exhibited mild pathological injury with no CK8^(+)cell proliferation.These results indicate a clear pulmonary cell remodeling route and suggest that CK8^(+)DATP cells play a primary role in mediating alveolar remodeling,highlighting their potential applications as diagnostic markers and therapeutic targets.

An exponential for the solutions model of collocation method of the HIV infection CD4＋T cells

In this paper, an exponential method is presented for the approximate solutions of the HIV infection model of CD4＋T. The method is based on exponential polynomi- als and collocation points. This model problem corresponds to a system of nonlinear ordinary differential equations. Matrix relations are constructed for the exponential functions. By aid of these matrix relations and the collocation points, the proposed technique transforms the model problem into a system of nonlinear algebraic equations. By solving the system of the algebraic equations, the unknown coefficients are com- puted and thus the approximate solutions are obtained. The applications of the method for the considered problem are given and the comparisons are made with the other methods.