Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut – namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor.

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Silica-based nanoparticles (NPs) pose great potential for medical and biological applications; however, their interactions with living cells have not been investigated in full. The objective of this study was to analyze the mechanical characteristics of mesenchymal stem cells when cultured in the presence of silica (Si) and silica-boron (SiB) nanoparticles. Cell stiffness was measured using atomic force microscopy; F-actin structure was evaluated using TRITC-phalloidin by confocal microscopy. The obtained data suggested that the cell stiffness increased within the following line: ‘Control’ - ‘Si’ - ‘SiB’ (either after 1-h cultivation or 24-h incubation). Moreover, the cell stiffness was found to be higher after 1-h cultivation as compared to 24-h cultivation. This result shows that there is a two-phase process of particle diffusion into cells and that the particles interact directly with the membrane and, further, with the submembranous cytoskeleton. Conversely, the intensity of phalloidin fluorescence dropped within the same line: Control - Si - SiB. It could be suggested that the effects of silica-based particles may result in structural reorganization of cortical cytoskeleton with subsequent stiffness increase and concomitant F-actin content decrease (for example, in recruitment of additional actin-binding proteins within membrane and regrouping of actin filaments).

High Intensity Focused Ultrasound (HIFU) is rapidly advancing as an alternative therapy for non-invasively treating specific cancers and other pathological tissues through thermal ablation. A new type of HIFU therapy – boiling histotripsy (BH) – aims at mechanical fractionation of into subcellular fragments, with a range of accompanying thermal effects that can be tuned from none to substantial depending on the requirements of the application. The degree of mechanical tissue damage induced by BH has been shown to depend on the tissue type, with collagenous structures being most resistant, and cellular structures being most sensitive. This has been reported for single BH lesions, but has not been replicated in large volumes. Such tissue selectivity effect has potential uses involving tissue decellularization for biofabrication technologies as well as mechanical ablation by BH while sparing critical structures. The goal of this study was to investigate tissue decellularization effect in larger, clinically relevant liquefied volumes of tissue, and to evaluate the accumulated thermal effect in the volumetric lesions under different exposure parameters. All BH exposures were performed with a 256-element 1.2 MHz array of a Magnetic Resonance Imaging –guided HIFU (MR-HIFU) clinical system (Sonalleve V1, Profound Medical Inc, Mississauga, Canada). The volumetric BH lesions were produced in degassed ex vivo bovine liver using 1–10-ms long pulses with in situ shock amplitudes of 75–100 MPa at the focus and pulse repetition frequencies (PRFs) of 1–10 Hz covering a range of effects from pure mechanical homogenization to thermal ablation. Multimodal analysis of the lesions was then performed, including microstructure (histological), ultrastructure (electron microscopy), and molecular (biochemistry) methods. Results show a range of tissue effects in terms of the degree of tissue selectivity and the amount of heat generated in large BH lesions, thereby demonstrating potential for treatments tailored to different clinical applications.