Increased amino acids in the dysbiotic gut influences susceptibility to Clostridioides difficile infection in mice and humans.

Conductive hydrogels are emerging as promising materials for electronic implants owing to their favorable mechanical and electrical properties. Poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels are particularly attractive, but their preparation often requires toxic additives. Here, we introduced a nutritive sweetener, d -sorbitol, as a nontoxic additive to create soft and stretchable PEDOT:PSS conductive hydrogels. These hydrogels exhibit mechanical properties comparable with biological tissues, reducing adverse immune responses. The hydrogels can be patterned on elastic substrates using a simple, low-cost micromolding technique to fabricate soft and stretchable implantable devices for electrical stimulation and recording. The hydrogel electrodes show much lower electrochemical impedance and higher charge storage and injection capacity compared to platinum electrodes. In addition, the properties of hydrogels and devices remain stable after long-term storage and exposure to extreme conditions. We demonstrate the use of soft hydrogel-based electronic devices for effective electrical stimulation and high-quality electrical recordings in live animal models.

Worldwide rates of Western-diet-induced obesity epidemics are growing dramatically. Being linked with numerous comorbidities and complications, including cardiovascular disease, type 2 diabetes, cancer, chronic inflammation, and osteoarthritis (OA), obesity represents one of the most threatening challenges for modern healthcare. Mouse models are an invaluable tool for investigating the effects of diets and their bioactive components against high fat diet (HFD)-induced obesity and its comorbidities. During recent years, very high fat diets (VHFDs), providing 58–60% kcal fat, have become a popular alternative to more traditional HFDs, providing 40–45% total kcal fat, due to the faster induction of obesity and stronger metabolic responses. This project aims to investigate if the 60% fat VHFD is suitable to evaluate the protective effects of curcumin in diet-induced obesity and osteoarthritis. B6 male mice, prone to diet-induced metabolic dysfunction, were supplemented with VHFD without or with curcumin for 13 weeks. Under these experimental conditions, feeding mice a VHFD for 13 weeks did not result in expected robust manifestations of the targeted pathophysiologic conditions. Supplementing the diet with curcumin, in turn, protected the animals against obesity without significant changes in white adipocyte size, glucose clearance, and knee cartilage integrity. Additional research is needed to optimize diet composition, curcumin dosage, and duration of dietary interventions to establish the VHFD-induced obesity for evaluating the effects of curcumin on metabolic dysfunctions related to obesity and osteoarthritis.

A wide range of viruses cause neurological manifestations in their hosts. Infection by neurotropic viruses as well as the resulting immune response can irreversibly disrupt the complex structural and functional architecture of the brain, depending in part on host genetic background. The interaction between host genetic background, neurological response to viral infection, and subsequent clinical manifestations remains poorly understood. In the present study, we used the genetically diverse Collaborative Cross (CC) mouse resource to better understand how differences in genetic background drive clinical signs and neuropathological manifestations of acute Theiler’s murine encephalomyelitis virus (TMEV) infection. For the first time, we characterized variations of TMEV viral tropism and load based on host genetic background, and correlated viral load with microglial/macrophage activation. For five CC strains (CC002, CC023, CC027, CC057, and CC078) infected with TMEV, we compared clinical signs, lesion distribution, microglial/macrophage response, expression, and distribution of TMEV mRNA, and identified genetic loci relevant to the early acute (4 days post-infection [dpi]) and late acute (14 dpi) timepoints. We examined brain pathology to determine possible causes of strain-specific differences in clinical signs, and found that fields CA1 and CA2 of the hippocampal formation were especially targeted by TMEV across all strains. Using Iba-1 immunolabeling, we identified and characterized strain- and timepoint-specific variation in microglial/macrophage reactivity in the hippocampal formation. Because viral clearance can influence disease outcome, we used RNA in situ hybridization to quantify viral load and TMEV mRNA distribution at both timepoints. TMEV mRNA expression was broadly distributed in the hippocampal formation at 4 dpi in all strains but varied between radiating and clustered distribution depending on the CC strain. We found a positive correlation between microglial/macrophage reactivity and TMEV mRNA expression at 4 dpi. At 14 dpi, we observed a dramatic reduction in TMEV mRNA expression, and localization to the medial portion of field CA1 and field CA2. To better understand how host genetic background can influence pathological outcomes, we identified quantitative trait loci associated with frequency of lesions in a particular brain region and with microglial/macrophage reactivity. These QTL were located near several loci of interest: lysosomal trafficking regulator (Lyst) and nidogen 1 (Nid1), and transmembrane protein 106 B (Tmem106b). Together, these results provide a novel understanding about the influences of genetic variation on the acute neuropathological and immunopathological environment and viral load, which collectively lead to variable disease outcomes. Our findings reveal possible avenues for future investigation which may lead to more effective intervention strategies and treatment regimens.