Modeling insights to navigate limitations in bipolar membranes
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PTN activity in quiescent neural stem cells mediates Shank3 overexpression-induced manic behavior
Mania is a complex psychiatric disease characterized by hyperactivity, elevated mood and reduced anxiety. Despite extensive studies on the mechanism of the manic episodes, the molecular targets that control manic pathogenesis remain largely unclear. Here, through single-cell RNA sequencing (scRNA-seq) analysis, we show aberrant adult neurogenesis due to increased numbers of quiescent neural stem cells (qNSC) in a manic mouse model with Shank3 overexpression. Particularly, we found that the excessive Pleiotrophin (PTN), released by dysregulated qNSCs, is a key factor contributing to the manic-like phenotypes in Shank3-overexpressing mouse models. Pharmacological and molecular inhibition of PTN in qNSCs rescued aberrant neurogenesis and effectively alleviated the manic-like social deficits observed in Shank3-overexpressing mice. Taken together, our findings present an approach for modulating PTN activity in qNSCs, proposing it as a promising therapeutic target for manic development.
Bipolar electrochemistry-driven wireless drug loading and energy harvesting in conductive hybrid hydrogels
Bipolar electrochemistry enables wireless and spatially controlled redox reactions on (semi)conductive objects immersed in an electrolyte. Here, we investigate advanced bipolar electrochemistry applications using flexible bipolar electrodes coated with hybrid films of conductive polymer poly(3,4-ethylenedioxythiophene) and alginate hydrogels. These coatings allow for the wireless creation of reversible redox and chemical gradients, providing targeted drug loading and energy harvesting opportunities. We use cyclic voltammetry, electrochemical impedance spectroscopy, Raman microscopy, and X-ray photoelectron spectroscopy to characterize distinct redox regions within the bipolar electrode. The wireless and selective loading of a model drug, fluorescein, into the hydrogel, demonstrated control over drug distribution, suggesting an alternative to conventional uniform doping techniques. Furthermore, cutting the gradient-encoded bipolar electrode and closing an external circuit between the halves, enables energy recovery through a concentration cell mechanism. Our findings illustrate the potential of bipolar electrochemistry in creating versatile platforms that bridge materials science, electrochemistry, and bioelectronics for innovative biomedical and energy applications.
Circular RNAs in neurological conditions – computational identification, functional validation, and potential clinical applications
Non-coding RNAs (ncRNAs) have gained significant attention in recent years due to advancements in biotechnology, particularly high-throughput total RNA sequencing. These developments have led to new understandings of non-coding biology, revealing that approximately 80% of non-coding regions in the genome possesses biochemical functionality. Among ncRNAs, circular RNAs (circRNAs), first identified in 1976, have emerged as a prominent research field. CircRNAs are abundant in most human cell types, evolutionary conserved, highly stable, and formed by back-splicing events which generate covalently closed ends. Notably, circRNAs exhibit high expression levels in neural tissue and perform diverse biochemical functions, including acting as molecular sponges for microRNAs, interacting with RNA-binding proteins to regulate their availability and activity, modulating transcription and splicing, and even translating into functional peptides in some cases. Recent advancements in computational and experimental methods have enhanced our ability to identify and validate circRNAs, providing valuable insights into their biological roles. This review focuses on recent developments in circRNA research as they related to neuropsychiatric and neurodegenerative conditions. We also explore their potential applications in clinical diagnostics, therapeutics, and future research directions. CircRNAs remain a relatively underexplored area of non-coding biology, particularly in the context of neurological disorders. However, emerging evidence supports their role as critical players in the etiology and molecular mechanisms of conditions such as schizophrenia, bipolar disorder, major depressive disorder, Alzheimer’s disease, and Parkinson’s disease. These findings suggest that circRNAs may provide a novel framework contributing to the molecular dysfunctions underpinning these complex neurological conditions.
Modeling the impact of structure and coverage on the reactivity of realistic heterogeneous catalysts
Adsorbates often cover the surfaces of catalysts densely as they carry out reactions, dynamically altering their structure and reactivity. Understanding adsorbate-induced phenomena and harnessing them in our broader quest for improved catalysts is a substantial challenge that is only beginning to be addressed. Here we chart a path toward a deeper understanding of such phenomena by focusing on emerging in silico modeling methodologies, which will increasingly incorporate machine learning techniques. We first examine how adsorption on catalyst surfaces can lead to local and even global structural changes spanning entire nanoparticles, and how this affects their reactivity. We then evaluate current efforts and the remaining challenges in developing robust and predictive simulations for modeling such behavior. Last, we provide our perspectives in four critical areas—integration of artificial intelligence, building robust catalysis informatics infrastructure, synergism with experimental characterization, and adaptive modeling frameworks—that we believe can help surmount the remaining challenges in rationally designing catalysts in light of these complex phenomena.
Polycystin-1 regulates tendon-derived mesenchymal stem cells fate and matrix organization in heterotopic ossification
Mechanical stress modulates bone formation and organization of the extracellular matrix (ECM), the interaction of which affects heterotopic ossification (HO). However, the mechanically sensitive cell populations in HO and the underlying mechanism remain elusive. Here, we show that the mechanical protein Polysyctin-1 (PC1, Pkd1) regulates CTSK lineage tendon-derived mesenchymal stem cell (TDMSC) fate and ECM organization, thus affecting HO progression. First, we revealed that CTSK lineage TDMSCs are the major source of osteoblasts and fibroblasts in HO and are responsive to mechanical cues via single-cell RNA sequencing analysis and experiments with a lineage tracing mouse model. Moreover, we showed that PC1 mediates the mechanosignal transduction of CTSK lineage TDMSCs to regulate osteogenic and fibrogenic differentiation and alters the ECM architecture by facilitating TAZ nuclear translocation. Conditional gene depletion of Pkd1 or Taz in CTSK lineage cells and pharmaceutical intervention in the PC1-TAZ axis disrupt osteogenesis, fibrogenesis and ECM organization, and consequently attenuate HO progression. These findings suggest that mechanically sensitive CTSK-lineage TDMSCs contribute to heterotopic ossification through PC1-TAZ signaling axis mediated cell fate determination and ECM organization.
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