Update on the Fungal Biofilm Drug Resistance and Its Alternative Treatment

Candida albicans (C. albicans) and Aspergillus fumigatus (A. fumigatus) are the two main pathogens in the clinical setting to cause serious, sometimes, lethal fungal infections. Immunocompromised patients fall victims to these fungi, with a mortality rate rising drastically over the past decades. This is in correlation with the fact that conventional antifungals are no longer capable of completely eradicating the disease, or if so, high doses are usually required to do so, leading to eventual resistance to those drugs and severe side effects. High drug resistance is in association with the discovery that these opportunistic pathogens have the ability to develop a multicellular complex, known as biofilm. Biofilms prevent drugs from reaching the fungal cells by sequestering them in their extracellular matrix. Other factors such as extracellular DNA, persister cells or heat shock protein 90 (Hsp90) also play a role in biofilm and contribute to drug recalcitrance. With the discovery of new antifungals lagging behind, scientists focused on other more profitable ways to counteract this phenomenon. Combination of two or more antifungals was found effective but came with serious drawbacks. Natural plant extracts, such as traditional Chinese medicine have also been demonstrated in vitro to possess antimicrobial actions. Great interest was directed towards their use with conventional antifungal agents with a possibility of lowering the necessary concentration required to inhibit the growth of fungi. This review aims in understanding the different factors contributing to clinical drug resistance and evaluating the effect of combination therapy and natural products on those cases difficult to treat.

MODIFIED SPLIT-STEP THETA METHOD FOR STOCHASTIC DIFFERENTIAL EQUATIONS DRIVEN BY FRACTIONAL BROWNIAN MOTION

For solving the stochastic differential equations driven by fractional Brownian motion,we present the modified split-step theta method by combining truncated Euler-Maruyama method with split-step theta method.For the problem under a locally Lipschitz condition and a linear growth condition,we analyze the strong convergence and the exponential stability of the proposed method.Moreover,for the stochastic delay differential equations with locally Lipschitz drift condition and globally Lipschitz diffusion condition,we give the order of convergence.Finally,numerical experiments are done to confirm the theoretical conclusions.

A DIRECT DISCONTINUOUS GALERKIN METHOD FOR TIME FRACTIONAL DIFFUSION EQUATIONS WITH FRACTIONAL DYNAMIC BOUNDARY CONDITIONS

This paper deals with the numerical approximation for the time fractional diffusion problem with fractional dynamic boundary conditions.The well-posedness for the weak solutions is studied.A direct discontinuous Galerkin approach is used in spatial direction under the uniform meshes,together with a second-order Alikhanov scheme is utilized in temporal direction on the graded mesh,and then the fully discrete scheme is constructed.Furthermore,the stability and the error estimate for the full scheme are analyzed in detail.Numerical experiments are also given to illustrate the effectiveness of the proposed method.

Epidemiology of fungal infections in China

Abstract With the increasing number of immunocompromised hosts, the epidemiological characteristics of fungal infections have undergone enormous changes worldwide, including in China. In this paper, we reviewed the existing data on mycosis across China to summarize available epidemiological profiles. We found that the general incidence of superficial fungal infections in China has been stable, but the incidence of tinea capitis has decreased and the transmission route has changed. By contrast, the overall incidence of invasive fungal infections has continued to rise. The occurrence of candidemia caused by Candida species other than C. albicans and including some uncommon Candida species has increased recently in China. Infections caused by Aspergillus have also propagated in recent years, particularly with the emergence of azole-resistant Aspergillusfumigatus. An increasing trend of cryptococcosis has been noted in China, with Cryptococcus neoformans var. grubii ST 5 genotype isolates as the predominant pathogen. Retrospective studies have suggested that the epidemiological characteristics of Pneumocystis pneumonia in China may be similar to those in other developing countries. Endemic fungal infections, such as sporotrichosis in Northeastern China, must arouse research, diagnostic, and treatment vigilance. Currently, the epidemiological data on mycosis in China are variable and fragmentary. Thus, a nationwide epidemiological research on fungal infections in China is an important need for improving the country＇s health.

The resurgent landscape of xenotransplantation of pig organs in nonhuman primates

Organ shortage is a major bottleneck in allotransplantation and causes many wait-listed patients to die or become too sick for transplantation.Genetically engineered pigs have been discussed as a potential alternative to allogeneic donor organs.Although xenotransplantation of pig-derived organs in nonhuman primates(NHPs)has shown sequential advances in recent years,there are still underlying problems that need to be completely addressed before clinical applications,including(i)acute humoral xenograft rejection;(ii)acute cellular rejection;(iii)dysregulation of coagulation and inflammation;(iv)physiological incompatibility;and(v)cross-species infection.Moreover,various genetic modifications to the pig donor need to be fully characterized,with the aim of identifying the ideal transgene combination for upcoming clinical trials.In addition,suitable pretransplant screening methods need to be confirmed for optimal donor-recipient matching,ensuring a good outcome from xenotransplantation.Herein,we summarize the understanding of organ xenotransplantation in pigs-to-NHPs and highlight the current status and recent progress in extending the survival time of pig xenografts and recipients.We also discuss practical strategies for overcoming the obstacles to xenotransplantation mentioned above to further advance transplantation of pig organs in the clinic.

A Modified KernelMethod for Solving Cauchy Problem of Two-Dimensional Heat Conduction Equation

In this paper,a Cauchy problem of two-dimensional heat conduction equation is investigated.This is a severely iⅡ-posed problem.Based on the solution of Cauchy problem of two-dimensional heat conduction equation,we propose to solve this problem by modifying the kernel,which generates a well-posed problem.Error estimates between the exact solution and the regularized solution are given.We provide a numerical experiment to illustrate the main results.