Background— A variety of studies carried out using either human subjects or laboratory animals suggest that vitamin D and its analogues possess important beneficial activity in the cardiovascular system. Using Cre-Lox technology we have selectively deleted receptor (VDR) gene cardiac myocyte an effort to better understand role regulating structure function. Methods Results— Targeted deletion exon 4 coding sequence VDR resulted increase size left ventricular weight/body weight versus controls...

In various mammalian species, including humans, water restriction leads to an acute increase in urinary sodium excretion. This process, known as dehydration natriuresis, helps prevent further accentuation of hypernatremia and the accompanying rise extracellular tonicity. Serum- glucocorticoid-inducible kinase (Sgk1), which is expressed renal medulla, regulated by However, mechanism its regulation physiological role hypertonicity-induced SGK1 gene expression remain unclear. Here, we...

The liganded vitamin D receptor (VDR) is thought to play an important role in controlling cardiac function. Specifically, this system has been implicated as playing antihypertrophic the heart. Despite this, studies of VDR heart have limited number and scope. In present study, we used a combination real-time polymerase chain reaction, Western blot analysis, immunofluorescence, transient transfection analysis document presence functional both myocytes fibroblasts heart, well intact ventricular...

Self-amplifying RNA (saRNA) vaccines are highly advantageous, as they result in enhanced protein expression compared to mRNA (mRNA), thus minimizing the required dose. However, previous delivery strategies were optimized for siRNA or and do not necessarily deliver saRNA efficiently due structural differences of these RNAs, motivating development platforms. Here, we engineer a bioreducible, linear, cationic polymer called "pABOL" show that increasing its molecular weight enhances both vitro...

The recently discovered CRISPR-Cas gene editing system and its derivatives have found numerous applications in fundamental biology research pharmaceutical sciences. need for precise external control over the regulatory events has driven development of inducible systems. While most light-controllable systems are based on protein engineering, we developed an alternative synthetic approach modification crRNA/tracrRNA duplex (guide RNA or gRNA) with photocaging groups, preventing gRNA from...

Abstract The development of near‐infrared light responsive conductive polymers provides a useful theranostic platform for malignant tumors by maximizing spatial resolution with deep tissue penetration diagnosis and photothermal therapy. Herein, the self‐assembly ultrathin 2D polypyrrole nanosheets utilizing dopamine as capping agent monolayer octadecylamine template is demonstrated. polypyrrole‐polydopamine nanostructure has tunable size distribution which shows strong absorption in first...

Abstract The unique electrochemical properties of the conductive polymer poly(3,4‐ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) make it an attractive material for use in neural tissue engineering applications. However, inadequate mechanical properties, and difficulties processing lack biodegradability have hindered progress this field. Here, functionality PEDOT:PSS is improved by incorporating 3,4‐ethylenedioxythiophene (EDOT) oligomers, synthesized using a novel end‐capping...

3D organoids are widely used as tractable in vitro models capable of elucidating aspects human development and disease. However, the manual low-throughput culture methods, coupled with a low reproducibility geometric heterogeneity, restrict scope application organoid research. Combining expertise from stem cell biology bioengineering offers promising approach to address some these limitations. Here, melt electrospinning writing is generate tuneable grid scaffolds that can guide...

The future of genetic medicine hinges on successful intracellular delivery nucleic acid-based therapeutics. While significant effort has concentrated developing nanocarriers to improve the aspects, scant attention been paid synthetic process poorly controlled nanocomplex formation. Proposed here is a reliable system better control complexation process, and thus physical properties nanocomplexes, through microfluidics-assisted confinement (MAC) in picoliter droplets. We show that these...

Transdifferentiation, where differentiated cells are reprogrammed into another lineage without going through an intermediate proliferative stem cell-like stage, is the next frontier of regenerative medicine. Wernig et al. first described direct conversion fibroblasts functional induced neuronal (iNs). Subsequent reports transdifferentiation clinically relevant subtypes have further endorsed prospect autologous cell therapy for neurodegenerative disorders. So far, all published protocols rely...

Successful intracellular delivery of nucleic acid therapeutics relies on multiaspect optimization, one which is formulation. While there has been ample innovation chemical design polymeric gene carriers, the same cannot be said for physical processing polymer-DNA nanocomplexes (polyplexes). Conventional synthesis polyplexes by bulk mixing depends operators' experience. The poorly controlled process may also lead to batch-to-batch variation and consequent irreproducibility. Here, we...

Shape-controlled synthesis of nanomaterials through a simple, continuous, and low-cost method is essential to research toward practical applications. Hydrodynamic focusing, with its advantages simplicity, low-cost, precise control over reaction conditions, has been used for nanomaterial synthesis. While most studies have focused on improving the uniformity size control, few addressed potential tuning shape synthesized nanomaterials. Here we demonstrate facile synthesize hybrid materials by...

As the designs of polymer systems used to deliver nucleic acids continue evolve, it is becoming increasingly apparent that basic bulk manufacturing techniques past will be insufficient produce polymer-nucleic acid nanocomplexes possess uniformity, stability and potency required for their successful clinical translation widespread commercialization. Traditional bulk-prepared products are often physicochemically heterogeneous may vary significantly from one batch next. Here we show preparation...

Skeletal muscle cells contain hundreds of myonuclei within a shared cytoplasm, presenting unique challenges for regulating gene expression. Certain transcriptional programs (e.g., postsynaptic machinery) are segregated to specialized domains, while others contractile proteins) do not show spatial confinement. Furthermore, local stimuli, such as denervation, can induce responses that propagated along the cells. Regulated transport nuclear proteins transcription factors) between represents...

Liver X receptors (LXRs) and their ligands are potent regulators of midbrain dopaminergic (mDA) neurogenesis differentiation. However, the molecular mechanisms by which LXRs control these functions remain to be elucidated. Here, we perform a combined transcriptome chromatin immunoprecipitation sequencing (ChIP-seq) analysis cells after LXR activation, followed bioinformatic elucidate transcriptional networks controlling mDA neurogenesis. Our results identify basic helix-loop-helix...

Abstract Non‐viral vectors represent versatile and immunologically safer alternatives for nucleic acid delivery. Nanoneedles high‐aspect ratio nanostructures are unconventional but interesting delivery systems, in which is mediated by surface interactions. Herein, nanoneedles synergistically combined with polysaccharide‐polyplex nanofilms enhanced transfection efficiency observed, compared to polyplexes suspension. Different polyplex‐polyelectrolyte nanofilm combinations assessed it found...

Using high-throughput screening, we were able to identify topographies that can significantly improve the efficiency of nonviral neuronal reprogramming.