Smooth Muscle Cells-Expressed Bmal1 Regulates Vascular Calcification Independent of the Canonical Circadian Pathway.

Vascular calcification is a major cardiovascular issue that increases morbidity and mortality in diabetes patients. While dysregulation of the circadian master regulator Basic Helix-Loop-Helix ARNT-Like Protein 1 (Bmal1) in vascular smooth muscle cells (VSMC) under diabetic conditions has been suggested, its role in vascular calcification is unclear. In VSMC, Bmal1 was upregulated under high glucose treatment and in aortic tissues from a diabetic mouse model. RNA sequencing from isolated VSMC between Bmal1 deletion and wildtype mice indicated Bmal1's pro-calcification role. Indeed, reduced levels of the osteogenic master regulator, Runt-Related Transcription Factor 2 (Runx2), were found in Bmal1 deletion VSMC under diabetic conditions. Alizarin red staining showed reduced calcification in Bmal1 deletion VSMC in vitro and vascular rings ex vivo . Furthermore, in a diabetic mouse model, SMC-Bmal1 deletion showed reduced calcium deposition in aortas. Collectively, diabetes-upregulated circadian regulator Bmal1 in VSMC contributes to vascular calcification. Maintaining normal circadian regulation may improve vascular health in diabetes.

Ribonuclease 4 functions as an intestinal antimicrobial protein to maintain gut microbiota and metabolite homeostasis.

Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.

Personalization Characteristics and Evaluation of Gamified Exercise for Middle-Aged and Older People: A Scoping Review.

Many studies have shown that personalized exergames have a positive effect on promoting regular and proper exercise. However, there is no consensus on the design characteristics and evaluation of exergames. This systematic review of published research literature aimed to explore the general characteristics, personalization characteristics, and evaluation of personalized exergames for middle-aged and older people. We screened published studies in the Web of Science, Scopus, PubMed, ACM, and IEEE Xplore databases, extracted data, and performed a thematic analysis according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist. Three main themes and nine subthemes were generated from 24 included papers. Moreover, a personalization model (FACTS) and evaluation system (PMSS) of exergames were developed. Personalized exergames had potential positive effects on motivating middle-aged and older people to exercise and improve their health, particularly physical, mental, and social health. However, more fine-grained studies on personalized exergames are necessary in the future.

Edge and Interface Resistances Create Distinct Trade-Offs When Optimizing the Microstructure of Printed van der Waals Thin-Film Transistors.

Inks based on two-dimensional (2D) materials could be used to tune the properties of printed electronics while maintaining compatibility with scalable manufacturing processes. However, a very wide range of performances have been reported in printed thin-film transistors in which the 2D channel material exhibits considerable variation in microstructure. The lack of quantitative physics-based relationships between film microstructure and transistor performance limits the codesign of exfoliation, sorting, and printing processes to inefficient empirical approaches. To rationally guide the development of 2D inks and related processing, we report a gate-dependent resistor network model that establishes distinct microstructure-performance relationships created by near-edge and intersheet resistances in printed van der Waals thin-film transistors. The model is calibrated by analyzing electrical output characteristics of model transistors consisting of overlapping 2D nanosheets with varied thicknesses that are mechanically exfoliated and transferred. Kelvin probe force microscopy analysis on the model transistors leads to the discovery that the nanosheet edges, not the intersheet resistance, limit transport due to their impact on charge carrier depletion and scattering. Our model suggests that when transport in a 2D material network is limited by the near-edge resistance, the optimum nanosheet thickness is dictated by a trade-off between charged impurity screening and gate screening, and the film mobilities are more sensitive to variations in printed nanosheet density. Removal of edge states can enable the realization of higher mobilities with thinner nanosheets due to reduced junction resistances and reduced gate screening. Our analysis of the influence of nanosheet edges on the effective film mobility not only examines the prospects of extant exfoliation methods to achieve the optimum microstructure but also provides important perspectives on processes that are essential to maximizing printed film performance.

All-Printed Ultrahigh-Responsivity MoS2 Nanosheet Photodetectors Enabled by Megasonic Exfoliation.

Printed 2D materials, derived from solution-processed inks, offer scalable and cost-effective routes to mechanically flexible optoelectronics. With micrometer-scale control and broad processing latitude, aerosol-jet printing (AJP) is of particular interest for all-printed circuits and systems. Here, AJP is utilized to achieve ultrahigh-responsivity photodetectors consisting of well-aligned, percolating networks of semiconducting MoS2 nanosheets and graphene electrodes on flexible polyimide substrates. Ultrathin (≈1.2 nm thick) and high-aspect-ratio (≈1 µm lateral size) MoS2 nanosheets are obtained by electrochemical intercalation followed by megasonic atomization during AJP, which not only aerosolizes the inks but also further exfoliates the nanosheets. The incorporation of the high-boiling-point solvent terpineol into the MoS2 ink is critical for achieving a highly aligned and flat thin-film morphology following AJP as confirmed by grazing-incidence wide-angle X-ray scattering and atomic force microscopy. Following AJP, curing is achieved with photonic annealing, which yields quasi-ohmic contacts and photoactive channels with responsivities exceeding 103  A W-1 that outperform previously reported all-printed visible-light photodetectors by over three orders of magnitude. Megasonic exfoliation coupled with properly designed AJP ink formulations enables the superlative optoelectronic properties of ultrathin MoS2 nanosheets to be preserved and exploited for the scalable additive manufacturing of mechanically flexible optoelectronics.

Photoelectrochemical Properties and Behavior of α-SnWO4 Photoanodes Synthesized by Hydrothermal Conversion of WO3 Films.

Metal oxides with moderate band gaps are desired for efficient production of hydrogen from sunlight and water via photoelectrochemical (PEC) water splitting. Here, we report an α-SnWO4 photoanode synthesized by hydrothermal conversion of WO3 films that achieves photon to current conversion at wavelengths up to 700 nm (1.78 eV). This photoanode is promising for overall PEC water-splitting because the flat-band potential and voltage of photocurrent onset are more negative than the potential of hydrogen evolution. Furthermore, the photoanode utilizes a large portion of the solar spectrum. However, the photocurrent density reaches only a small fraction of that which is theoretically possible. Density functional theory based thermodynamic and electronic structure calculations were performed to elucidate the nature and impact of defects in α-SnWO4 prepared by this synthetic route, from which hole localization at Sn-at-W antisite defects was determined to be a likely cause for the poor photocurrent. Measurements further showed that the photocurrent decreases over time due to surface oxidation, which was suppressed by improving the kinetics of hole transfer at the semiconductor/electrolyte interface. Alternative synthetic methods and the addition of protective coatings and/or oxygen evolution catalysts are suggested to improve the PEC performance and stability of this promising α-SnWO4 material.