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Acoustic metamaterials based on out‐of‐plane actuation can flexibly reconfigure arrayed unit cells on demand, to shape sound fields for applications such as beam formation or holography. However, implementing active reconfiguration on the millimeter‐scale is challenging, due to the lack of suitable actuation methods. Besides electronic complexity, current methods suffer from limited actuation range (sub‐millimeter), and discrete steps inhibit smooth sound modulation. Here, a novel fluid‐driven approach for continuous out‐of‐plane actuation is presented. A three dimensionally (3D)‐printed fluidic chip is integrated with an elastomeric membrane, and selective inflation of membrane sections actuates acoustic reflector unit cells according to their shape and position. The compact device enables displacements >5 mm without coupling mechanisms or external power. It is experimentally demonstrate single‐channel and multi‐channel prototypes, including an ultrasonic metasurface built for controllable acoustic focusing at five different locations. The fluidic chips are monolithically printed via digital light processing without internal support material, and the membranes are fabricated by accessible and cost‐effective spacer‐based fabrication. The methods are reproducible and eliminate complex processes (e.g., adhesion of layers) commonly associated with multi‐layered micro/milli fluidic devices. The outlined approaches and concepts in this work can be applied beyond the field of metamaterials, such as for visual displays, or tactile devices. [ABSTRACT FROM AUTHOR]

UnlabelledMice deficient in small heterodimer partner (SHP) are protected from diet-induced hepatic steatosis resulting from increased fatty acid oxidation and decreased lipogenesis. The decreased lipogenesis appears to be a direct consequence of very low expression of peroxisome proliferator-activated receptor gamma 2 (PPAR-γ2), a potent lipogenic transcription factor, in the SHP(-/-) liver. The current study focused on the identification of a SHP-dependent regulatory cascade that controls PPAR-γ2 gene expression, thereby regulating hepatic fat accumulation. Illumina BeadChip array (Illumina, Inc., San Diego, CA) and real-time polymerase chain reaction were used to identify genes responsible for the linkage between SHP and PPAR-γ2 using hepatic RNAs isolated from SHP(-/-) and SHP-overexpressing mice. The initial efforts identify that hairy and enhancer of split 6 (Hes6), a novel transcriptional repressor, is an important mediator of the regulation of PPAR-γ2 transcription by SHP. The Hes6 promoter is specifically activated by the retinoic acid receptor (RAR) in response to its natural agonist ligand, all-trans retinoic acid (atRA), and is repressed by SHP. Hes6 subsequently represses hepatocyte nuclear factor 4 alpha (HNF-4α)-activated PPAR-γ2 gene expression by direct inhibition of HNF-4α transcriptional activity. Furthermore, we provide evidences that atRA treatment or adenovirus-mediated RAR-α overexpression significantly reduced hepatic fat accumulation in obese mouse models, as observed in earlier studies, and the beneficial effect is achieved by the proposed transcriptional cascade.ConclusionsOur study describes a novel transcriptional regulatory cascade controlling hepatic lipid metabolism that identifies retinoic acid signaling as a new therapeutic approach to nonalcoholic fatty liver diseases.

High‐quality acousto‐holographic patterns and images, integral to applications like 3D displays, acoustophoresis, and midair haptics, require precise distribution of ultrasound waves to achieve. Essential tools for this task are spatial sound modulators (SSMs), which control constituent elements to enable dynamic distribution of sound pressure. However, current ultrasonic SSMs face limitations due to high costs and the intricate actuation of numerous small, closely spaced units. This study introduces "segmented SSMs," novel devices that combine traditional acoustic metasurface pixel units into custom‐shaped segmented elements. These segmented SSMs reduce actuation costs and complexity while retaining pressure distribution quality. This approach includes a custom phase agglomeration algorithm (PAA), that offers a hierarchy of potential segmentation solutions for user selection. An SSM fabrication method is detailed using off‐the‐shelf 3D printers and bespoke control electronics, completing an end‐to‐end methodology from conception to realization. This approach is validated with two prototype SSM devices that focus sound waves and levitate polystyrene beads using dynamic segmented elements. Further enhancements to the technique are explored through hybrid SSM devices with both static and dynamic elements. The pipeline facilitates efficient SSM construction across diverse applications and invites the inception of future devices with varying sizes, uses, and actuation mechanisms. [ABSTRACT FROM AUTHOR]

In many mammalian species, the intestinal epithelium undergoes major changes that allow a dietary transition from mother's milk to the adult diet at the end of the suckling period. These complex developmental changes are the result of a genetic programme intrinsic to the gut tube, but its regulators have not been identified. Here we show that transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp1) is highly expressed in the developing and postnatal intestinal epithelium until the suckling to weaning transition. Intestine-specific deletion of Blimp1 results in growth retardation and excessive neonatal mortality. Mutant mice lack all of the typical epithelial features of the suckling period and are born with features of an adult-like intestine. We conclude that the suckling to weaning transition is regulated by a single transcriptional repressor that delays epithelial maturation.

Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR) is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO) to the Apc(Min/+) mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+) mice exhibited no change in polyp number, size or localization compared to Apc(Min/+). To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis.

In gastric cancer, a new epigenetic mechanism of tumour suppressor loss has been suggested where the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is responsible for loss of expression of RUNX3. This is consistent with EZH2 upregulation in multiple cancer types being associated with poor prognosis. We investigated whether EZH2 influences the expression of RUNX3 in colorectal cancer (CRC) and whether this is independent of methylation. We determined protein and messenger RNA (mRNA) levels of EZH2 and RUNX3 and assessed RUNX3 methylation with methylation-specific polymerase chain reaction using 72 human CRCs and 8 CRC cell lines. We assessed the effect of efficient RNA interference-mediated knockdown of EZH2 on RUNX3 levels, cell viability and H3K27 trimethylation of the RUNX3 promoter using chromatin immunoprecipitation. Despite higher levels of EZH2 and lower levels of RUNX3 in CRC specimens in general, no inverse correlation between EZH2 and RUNX3 in paired samples was found arguing against a major role for histone methylation in silencing RUNX3 in CRC. Conversely, downregulation of RUNX3 mRNA in the same tumours was associated with RUNX3 DNA methylation (P < 0.05). In cell lines, knockdown of EZH2 removed the repressive chromatin marks from RUNX3 but did not result in RUNX3 re-expression. However, it prevented the re-silencing of RUNX3 after the removal of demethylating agents. In conclusion, DNA methylation is primarily responsible for the transcriptional silencing of RUNX3 in CRC, but EZH2 and histone methylation are necessary for its methylation-dependent re-silencing after the removal of demethylating agents. These results would predict that inhibitors of EZH2 and histone methylation would enhance the effects of demethylating agents in cancer therapy.