Satellite cell-specific ablation of Cdon impairs integrin activation, FGF signalling, and muscle regeneration

Background: Perturbation in cell adhesion and growth factor signalling in satellite cells results in decreased muscle regenerative capacity. Cdon (also called Cdo) is a component of cell adhesion complexes implicated in myogenic differentiation, but its role in muscle regeneration remains to be determined. Methods: We generated inducible satellite cell-specific Cdon ablation in mice by utilizing a conditional Cdon allele and Pax7 CreERT2. To induce Cdon ablation, mice were intraperitoneally injected with tamoxifen (tmx). Using cardiotoxin-induced muscle injury, the effect of Cdon depletion on satellite cell function was examined by histochemistry, immunostaining, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Isolated myofibers or myoblasts were utilized to determine stem cell function and senescence. To determine pathways related to Cdon deletion, injured muscles were subjected to RNA sequencing analysis. Results: Satellite cell-specific Cdon ablation causes impaired muscle regeneration with fibrosis, likely attributable to decreased proliferation, and senescence, of satellite cells. Cultured Cdon-depleted myofibers exhibited 32 ± 9.6% of EdU-positive satellite cells compared with 58 ± 4.4% satellite cells in control myofibers (P < 0.05). About 32.5 ± 3.7% Cdon-ablated myoblasts were positive for senescence-associated β-galactosidase (SA-β-gal) while only 3.6 ± 0.5% of control satellite cells were positive (P < 0.001). Transcriptome analysis of muscles at post-injury Day 4 revealed alterations in genes related to mitogen-activated protein kinase signalling (P < 8.29 e−5) and extracellular matrix (P < 2.65 e−24). Consistent with this, Cdon-depleted tibialis anterior muscles had reduced phosphorylated extracellular signal-regulated kinase (p-ERK) protein levels and expression of ERK targets, such as Fos (0.23-fold) and Egr1 (0.31-fold), relative to mock-treated control muscles (P < 0.001). Cdon-depleted myoblasts exhibited impaired ERK activation in response to basic fibroblast growth factor. Cdon ablation resulted in decreased and/or mislocalized integrin β1 activation in satellite cells (weak or mislocalized integrin1 in tmx = 38.7 ± 1.9%, mock = 21.5 ± 6%, P < 0.05), previously linked with reduced fibroblast growth factor (FGF) responsiveness in aged satellite cells. In mechanistic studies, Cdon interacted with and regulated cell surface localization of FGFR1 and FGFR4, likely contributing to FGF responsiveness of satellite cells. Satellite cells from a progeria model, Zmpste24−/− myofibers, showed decreased Cdon levels (Cdon-positive cells in Zmpste24−/− = 63.3 ± 11%, wild type = 90 ± 7.7%, P < 0.05) and integrin β1 activation (weak or mislocalized integrin β1 in Zmpste24−/− = 64 ± 6.9%, wild type = 17.4 ± 5.9%, P < 0.01). Conclusions: Cdon deficiency in satellite cells causes impaired proliferation of satellite cells and muscle regeneration via aberrant integrin and FGFR signalling. © 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders1

In Vivo Expression of Reprogramming Factors Increases Hippocampal Neurogenesis and Synaptic Plasticity in Chronic Hypoxic-Ischemic Brain Injury

Neurogenesis and synaptic plasticity can be stimulated in vivo in the brain. In this study, we hypothesized that in vivo expression of reprogramming factors such as Klf4, Sox2, Oct4, and c-Myc would facilitate endogenous neurogenesis and functional recovery. CD-1® mice were induced at 1 week of age by unilaterally carotid artery ligation and exposure to hypoxia. At 6 weeks of age, mice were injected GFP only or both four reprogramming factors and GFP into lateral ventricle. Passive avoidance task and open field test were performed to evaluate neurobehavioral function. Neurogenesis and synaptic activity in the hippocampus were evaluated using immunohistochemistry, qRT-PCR, and/or western blot analyses. Whereas BrdU+GFAP+ cells in the subgranular zone of the hippocampus were not significantly different, the numbers of BrdU+βIII-tubulin+ and BrdU+NeuN+ cells were significantly higher in treatment group than control group. Expressions of synaptophysin and PSD-95 were also higher in treatment group than control group. Importantly, passive avoidance task and open field test showed improvement in long-term memory and decreased anxiety in treatment group. In conclusion, in vivo expression of reprogramming factors improved behavioral functions in chronic hypoxic-ischemic brain injury. The mechanisms underlying these repair processes included endogenous neurogenesis and synaptic plasticity in the hippocampus

A Semi‐Crystalline Polymer Semiconductor with Thin Film Stretchability Exceeding 200%

Abstract Despite the emerging scientific interest in polymer‐based stretchable electronics, the trade‐off between the crystallinity and stretchability of intrinsically stretchable polymer semiconductors—charge‐carrier mobility increases as crystallinity increases while stretchability decreases—hinders the development of high‐performance stretchable electronics. Herein, a highly stretchable polymer semiconductor is reported that shows concurrently improved thin film crystallinity and stretchability upon thermal annealing. The polymer thin films annealed at temperatures higher than their crystallization temperatures exhibit substantially improved thin film stretchability (> 200%) and hole mobility (≥ 0.2 cm2 V−1 s−1). The simultaneous enhancement of the crystallinity and stretchability is attributed to the thermally‐assisted structural phase transition that allows the formation of edge‐on crystallites and reinforces interchain noncovalent interactions. These results provide new insights into how the current crystallinity–stretchability limitation can be overcome. Furthermore, the results will facilitate the design of high‐mobility stretchable polymer semiconductors for high‐performance stretchable electronics

Large Transconductance of Electrochemical Transistors Based on Fluorinated Donor-Acceptor Conjugated Polymers

Organic electrochemical transistors (OECTs) have enor-mous potential for use in biosignal amplifiers, analyte sensors, and neuromorphic electronics owing to their exceptionally large trans-conductance. However, it is challenging to simultaneously achieve high charge carrier mobility and volumetric capacitance, the two most important figures of merit in OECTs. Herein, a method of achieving high-performance OECT with donor-acceptor conjugated copolymers by introducing fluorine units is proposed. A series of cyclopentadithiophene- benzothiadiazole (CDT-BT) copolymers for use in high-performance OECTs with enhanced charge carrier mobility (from 0.65 to 1.73 cm2 center dot V-1 center dot s-1) and extended volumetric capacitance (from 44.8 to 57.6 F center dot cm-3) by fluorine substitution is achieved. The increase in the volumetric capacitance of the fluorinated polymers is attributed to either an increase in the volume at which ions can enter the film or a decrease in the effective distance between the ions and polymer backbones. The fluorine substitution increases the backbone planarity of the CDT-BT copolymers, enabling more efficient charge carrier transport. The fluorination strategy of this work suggests the more versatile use of conjugated polymers for high-performance OECTs

Utilizing a Siloxane-Modified Organic Semiconductor for Photoelectrochemical Water Splitting

Weexplore the potential of employing diketopyrrolopyrrole (DPP)based pi-conjugated OSs as a hole transport layer material inheteroatom-doped hematite (Ti-Fe2O3/Ge-Fe2O3) photoanodes for efficient photoelectrochemicalwater splitting. The siloxane-modified pi-conjugated polymer(P-Si) with a high carrier mobility and crystallinity revealedgreat potential to extract holes by forming a built-in potential withhematite photoanodes while showing high stability in an alkaline electrolytefor photoelectrochemical water oxidation. Because of the easy holeextraction and subsequent fast hole transport property of the P-Si interlayer between NiFe-(OH)( x ) and Ge-doped porous Fe2O3(Ge-PH), NiFe-(OH)( x )/P-Si/Ge-PH showed a 1.8-fold increasein photocurrent density (4.57 mA cm(-2) at 1.23 V-RHE) with a cathodic shift of the onset potential (0.735 V-RHE) and good stability for 65 h compared to Ge-PH. This studydemonstrates the successful use of inherently unstable pi-conjugatedOSs as a hole extracting/transport medium in a photoanode, addressingthe intrinsic recombination issues of hematite for efficient and stablewater splitting

Disrupting FKF1 homodimerization increases FT transcript levels in the evening by enhancing CO stabilization

In Arabidopsis (Arabidopsis thaliana), the blue-light photoreceptor FKF1 (FLAVIN-BINDING, KELCH REPEAT, F-BOX 1) plays a key role in inducing the expression of FLOWERING LOCUS T (FT), encoding the main florigenic signal in plants, in the late afternoon under long-day conditions (LDs) by forming dimers with FT regulators. Although structural studies have unveiled a variant of FKF1 (FKF1 I160R) that disrupts homodimer formation in vitro, the mechanism by which disrupted FKF1 homodimer formation regulates flowering time remains elusive. In this study, we determined that the attenuation of FKF1 homodimer formation enhances FT expression in the evening by promoting the increased stability of CONSTANS (CO), a primary activator of FT, in the afternoon, thereby contributing to early flowering. In contrast to wild-type FKF1, introducing the FKF1 I160R variant into the fkf1 mutant led to increased FT expression under LDs. In addition, the FKF1 I160R variant exhibited diminished dimerization with FKF1, while its interaction with GIGANTEA (GI), a modulator of FKF1 function, was enhanced under LDs. Furthermore, the FKF1 I160R variant increased the level of CO in the afternoon under LDs by enhancing its binding to COP1, an E3 ubiquitin ligase responsible for CO degradation. These findings suggest that the regulation of FKF1 homodimerization and heterodimerization allows plants to finely adjust FT expression levels around dusk by modulating its interactions with GI and COP1.Y

Fluorescence-based immunosensor using three-dimensional CNT network structure for sensitive and reproducible detection of oral squamous cell carcinoma biomarker

A hierarchical three-dimensional network of carbon nanotubes on Si pillar substrate (3DN-CNTs) was developed for the accurate detection of oral squamous cell carcinoma (OSCC) in clinical saliva samples. The 3DN-CNTs were uniformly coated with a layer of aluminum oxides to enhance structural stability during biomarker detection. Cytokeratin-19 antigen (Cyfra 21-1) was utilized as a model biomarker of OSCC for fluorescence-based immunosensor using 3DN-CNTs (3DN-CNTs sensor). The 3DN-CNTs sensor enhances the sensitivity of Cyfra 21-1 detection by increasing the density of immobilized antibody through high surface area of 3DN-CNTs and enhancing the accessibility of biomolecules through the ordered pathway of hierarchical structure. The reliable detection limit for sensing of Cyfra 21-1 was estimated as in the level of 0.5 ng/mL and the quantitative estimation of Cyfra 21-1 was analyzed by 4-parameter logistic (4-PL) model for curve-fitting analysis. Clinical applicability of 3DN-CNTs sensor was evaluated through correlation with the commercially available electrochemiluminescence (ECL) detection system in the hospital. The assay results of the two systems for clinical saliva samples showed a good linear correlation. The 3DN-CNTs sensor offers great potential for accurate diagnosis of OSCC using Cyfra 21-1 biomarker in clinical fluids.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore

Chemically Engineered Au–Ag Plasmonic Nanostructures to Realize Large Area and Flexible Metamaterials

We developed a simple and systematic method to fabricate optically tunable and thermally and chemically stable Au–Ag nanocrystal-based plasmonic metamaterials. An Ag nanocrystal-based metamaterial with desirable optical properties was fabricated via nanoimprinting and ligand-exchange process. Its optical properties were controlled by selectively substituting Ag atoms with Au atoms through a spontaneous galvanic replacement reaction. The developed Au–Ag-based metamaterials provide excellent tunable plasmonic properties required for various applications in the visible and near-infrared regions by controlling the Au–Ag composition according to the conditions of the galvanic displacement. Furthermore, their thermal and chemical stabilities significantly improved because of the protective Au thin layer on the surface. Using this developed process, chemically and thermally stable and flexible plasmonic metamaterials were successfully fabricated on a flexible polyester terephthalate substrate