In this paper, a two-strain model that links immunological and epidemiological dynamics across scales is formulated. On the within-host scale, the two strains eliminate each other with the strain with the larger immunological reproduction persisting. However, on the population scale superinfection is possible, with the strain with larger immunological reproduction number super-infecting the strain with the smaller immunological reproduction number. The two models are linked through the age-since-infection structure of the epidemiological variables. In addition, the between-host transmission and the disease-induced death rate depend on the within-host viral load. The immunological reproduction numbers, the epidemiological reproduction numbers and invasion reproduction numbers are computed. Besides the disease-free equilibrium, there are two population-level strain one and strain two isolated equilibria, as well as a population-level coexistence equilibrium when both invasion reproduction numbers are greater than one. The single-strain population-level equilibria are locally asymptotically stable suggesting that in the absence of superinfection oscillations do not occur, a result contrasting previous studies of HIV age-since-infection structured models. Simulations suggest that the epidemiological reproduction number and HIV population prevalence are monotone functions of the within-host parameters with reciprocal trends. In particular, HIV medications that decrease within-host viral load also increase overall population prevalence. The effect of the immunological parameters on the population reproduction number and prevalence is more pronounced when the initial viral load is lower.

Diabetic foot, a main complication of diabetes mellitus, renders the foot susceptible to infection, and may eventually lead to non-traumatic limb amputation due to the deterioration of diabetic foot ulcers (DFUs). Characterizing the pathogen spectrum and antibiotic susceptibility is critical for the effective treatment of DFUs. In the current study, the characteristics and antibiotic susceptibility of the pathogen spectrum were analyzed. Secretions from the DFUs of 102 patients were cultured, and dominant pathogens were identified by using test cards. Antibiotic susceptibility of dominant pathogens was assayed by the Kirby–Bauer assay. We found that the dominant pathogens varied with age, duration of diabetes, blood sugar control, and the initial cause of ulcers. Moreover, the dominant pathogens were susceptible to at least one antibiotic. However, the antibacterial efficacy of several commonly used antibiotics decreased from 2016 to 2019. Our study indicates that the identification of dominant pathogens and antibiotic susceptibility testing is essential for the treatment of DFUs with effective antibiotics, while the abuse of antibiotics should be strictly restrained to reduce the generation of antibiotic-resistant strains.

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such as α-synuclein in neurons. As one of the major intracellular degradation pathways, the autophagy-lysosome pathway plays an important role in eliminating these proteins. Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance of α-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease. Moreover, multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway. Thus, this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease. In this review, we briefly introduce the machinery of autophagy. Then, we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway. Finally, we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.