Aryl Hydrocarbon Receptor Activation Coordinates Mouse Small Intestinal Epithelial Cell Programming.

In the face of mechanical, chemical, microbial, and immunologic pressure, intestinal homeostasis is maintained through balanced cellular turnover, proliferation, differentiation, and self-renewal. Here, we present evidence supporting the role of the aryl hydrocarbon receptor (AHR) in the adaptive reprogramming of small intestinal gene expression, leading to altered proliferation, lineage commitment, and remodeling of the cellular repertoire that comprises the intestinal epithelium to promote intestinal resilience. Ahr gene/protein expression and transcriptional activity exhibit marked proximalHI to distalLO and cryptHI to villiLO gradients. Genetic ablation of Ahr impairs commitment/differentiation of the secretory Paneth and goblet cell lineages and associated mucin production, restricts expression of secretory/enterocyte differentiation markers, and increases crypt-associated proliferation and villi-associated enterocyte luminal exfoliation. Ahr-/- mice display a decrease in intestinal barrier function. Ahr+/+ mice that maintain a diet devoid of AHR ligands intestinally phenocopy Ahr-/- mice. In contrast, Ahr+/+ mice exposed to AHR ligands reverse these phenotypes. Ligand-induced AHR transcriptional activity positively correlates with gene expression (Math1, Klf4, Tff3) associated with differentiation of the goblet cell secretory lineage. Math1 was identified as a direct target gene of AHR, a transcription factor critical to the development of goblet cells. These data suggest that dietary cues, relayed through the transcriptional activity of AHR, can reshape the cellular repertoire of the gastrointestinal tract.

Methods of ex vivo analysis of tissue status in vascularized composite allografts.

Vascularized composite allotransplantation can improve quality of life and restore functionality. However, the complex tissue composition of vascularized composite allografts (VCAs) presents unique clinical challenges that increase the likelihood of transplant rejection. Under prolonged static cold storage, highly damage-susceptible tissues such as muscle and nerve undergo irreversible degradation that may render allografts non-functional. Skin-containing VCA elicits an immunogenic response that increases the risk of recipient allograft rejection. The development of quantitative metrics to evaluate VCAs prior to and following transplantation are key to mitigating allograft rejection. Correspondingly, a broad range of bioanalytical methods have emerged to assess the progression of VCA rejection and characterize transplantation outcomes. To consolidate the current range of relevant technologies and expand on potential for development, methods to evaluate ex vivo VCA status are herein reviewed and comparatively assessed. The use of implantable physiological status monitoring biochips, non-invasive bioimpedance monitoring to assess edema, and deep learning algorithms to fuse disparate inputs to stratify VCAs are identified.

Real-Time Monitoring Using Multiplexed Multi-Electrode Bioelectrical Impedance Spectroscopy for the Stratification of Vascularized Composite Allografts: A Perspective on Predictive Analytics.

Vascularized composite allotransplantation addresses injuries to complex anatomical structures such as the face, hand, and abdominal wall. Prolonged static cold storage of vascularized composite allografts (VCA) incurs damage and imposes transportation limits to their viability and availability. Tissue ischemia, the major clinical indication, is strongly correlated with negative transplantation outcomes. Machine perfusion and normothermia can extend preservation times. This perspective introduces multiplexed multi-electrode bioimpedance spectroscopy (MMBIS), an established bioanalytical method to quantify the interaction of the electrical current with tissue components, capable of measuring tissue edema, as a quantitative, noninvasive, real-time, continuous monitoring technique to provide crucially needed assessment of graft preservation efficacy and viability. MMBIS must be developed, and appropriate models explored to address the highly complex multi-tissue structures and time-temperature changes of VCA. Combined with artificial intelligence (AI), MMBIS can serve to stratify allografts for improvement in transplantation outcomes.

LIDAR Assist Spatial Sensing for the Visually Impaired and Performance Analysis.

Echolocation enables people with impaired or no vision to comprehend the surrounding spatial information through the reflected sound. However, this technique often requires substantial training, and the accuracy of echolocation is subject to various conditions. Furthermore, the individuals who practice this sensing method must simultaneously generate the sound and process the received audio information. This paper proposes and evaluates a proof-of-concept light detection and ranging (LIDAR) assist spatial sensing (LASS) system, which intends to overcome these restrictions by obtaining the spatial information of the user's surroundings through a LIDAR sensor and translating the spatial information into the stereo sound of various pitches. The stereo sound of relative pitch represents the information regarding objects' angular orientation and horizontal distance, respectively, thus granting visually impaired users an enhanced spatial perception of his or her surrounding areas and potential obstacles. This paper is divided into two phases: Phase I is to engineer the hardware and software of the LASS system and Phase II focuses on the system efficacy study. The study, approved by the Penn State Institutional Review Board, included 18 student volunteers, who were recruited through the Penn State Department of Psychology Subject Pool. This paper demonstrates that the blindfolded individuals equipped with the LASS system are able to quantitatively identify the surrounding obstacles, differentiate their relative distance, and distinguish the angular location of multiple objects with minimal training.