Matrix Formation Research Articles

The p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop mediates vasoactive intestinal peptide effects on osteoarthritis chondrocytes.

Loss and dysfunction of articular chondrocytes, which disrupt the homeostasis of extracellular matrix formation and breakdown, promote the onset of osteoarthritis (OA). Targeting inflammatory pathways is an important therapeutic strategy for OA. Vasoactive intestinal peptide (VIP) is an immunosuppressive neuropeptide with potent anti-inflammatory effects; however, its role and mechanism in OA remain unclear. In this study, microarray expression profiling from the Gene Expression Omnibus database and integrative bioinformatics analyses were performed to identify differentially expressed lncRNAs in OA samples. qRT-PCR validation of the top ten different expressed lncRNAs indicated that the expression level of intergenic non-protein coding RNA 2203 (LINC02203, also named LOC727924) was the highest in OA cartilage compared to normal cartilage. Hence, the LOC727924 function was further investigated. LOC727924 was upregulated in OA chondrocytes, with a dominant sub-localization in the cytoplasm. In OA chondrocytes, LOC727924 knockdown boosted cell viability, suppressed cell apoptosis, reactive oxygen species (ROS) accumulation, increased aggrecan and collagen II, decreased matrix metallopeptidase (MMP)-3/13 and ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4/5 levels, and reduced the levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). LOC727924 could interact with the microRNA 26a (miR-26a)/ karyopherin subunit alpha 3 (KPNA3) axis by competitively targeting miR-26a for KPNA3 binding, therefore down-regulating miR-26a and upregulating KPNA3; in OA chondrocytes, miR-26a inhibition partially abolished LOC727924 knockdown effects on chondrocytes. miR-26a inhibited the nuclear translocation of p65 through targeting KPNA3 and p65 transcriptionally activated LOC727924, forming a p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop to modulate OA chondrocyte phenotypes. In vitro, VIP improved OA chondrocyte proliferation and functions, down-regulated LOC727924, KPNA3, and p65 expression, and upregulated miR-26a expression; in vivo, VIP ameliorated destabilization of the medial meniscus (DMM)-induced damages on the mouse knee joint, down-regulated KPNA3, inhibited the nuclear translocation of p65. In conclusion, the p65-LOC727924-miR-26a/KPNA3-p65 regulatory loop modulates OA chondrocyte apoptosis, ROS accumulation, extracellular matrix (ECM) deposition, and inflammatory response in vitro and OA development in vivo, being one of the mechanisms mediating VIP ameliorating OA.

Knockout of the Cardiac Transcription Factor NKX2-5 Results in Stem Cell-Derived Cardiac Cells with Typical Purkinje Cell-like Signal Transduction and Extracellular Matrix Formation.

The human heart controls blood flow, and therewith enables the adequate supply of oxygen and nutrients to the body. The correct function of the heart is coordinated by the interplay of different cardiac cell types. Thereby, one can distinguish between cells of the working myocardium, the pace-making cells in the sinoatrial node (SAN) and the conduction system cells in the AV-node, the His-bundle or the Purkinje fibres. Tissue-engineering approaches aim to generate hiPSC-derived cardiac tissues for disease modelling and therapeutic usage with a significant improvement in the differentiation quality of myocardium and pace-making cells. The differentiation of cells with cardiac conduction system properties is still challenging, and the produced cell mass and quality is poor. Here, we describe the generation of cardiac cells with properties of the cardiac conduction system, called conduction system-like cells (CSLC). As a primary approach, we introduced a CrispR-Cas9-directed knockout of the NKX2-5 gene in hiPSC. NKX2-5-deficient hiPSC showed altered connexin expression patterns characteristic for the cardiac conduction system with strong connexin 40 and connexin 43 expression and suppressed connexin 45 expression. Application of differentiation protocols for ventricular- or SAN-like cells could not reverse this connexin expression pattern, indicating a stable regulation by NKX2-5 on connexin expression. The contraction behaviour of the hiPSC-derived CSLCs was compared to hiPSC-derived ventricular- and SAN-like cells. We found that the contraction speed of CSLCs resembled the expected contraction rate of human conduction system cells. Overall contraction was reduced in differentiated cells derived from NKX2-5 knockout hiPSC. Comparative transcriptomic data suggest a specification of the cardiac subtype of CSLC that is distinctly different from ventricular or pacemaker-like cells with reduced myocardial gene expression and enhanced extracellular matrix formation for improved electrical insulation. In summary, knockout of NKX2-5 in hiPSC leads to enhanced differentiation of cells with cardiac conduction system features, including connexin expression and contraction behaviour.

DNA-Based Hydrogels with Multidrug Sequential Release for Promoting Diabetic Wound Regeneration.

Diabetic wound (DW) regeneration is highly challenging due to persistent bacterial infection, excessive production of reactive oxygen species (ROS), prolonged inflammatory response, and insufficient angiogenesis. Ideal management requires the integration and sequential release of bactericidal, antioxidative, anti-inflammatory, and angiogenic agents during DW repair. Here, we develop a DNA-based multidrug hydrogel, termed Agilegel, to promote the efficient healing of DW. Hierarchically structured Agilegel can precisely control the sequential release of vascular endothelial growth factor-alpha (VEGF-α), silver nanoclusters (AgNCs), and interleukin-10 (IL-10) through covalent bonds in its primary structure (phosphate backbone), noncovalent bonds in its secondary structure (base pairs), and physical encapsulation in its advanced structure (pores), respectively. We demonstrate that Agilegel can effectively eliminate bacterial infection through AgNCs and mitigate ROS production through DNA scaffolds. Moreover, during the inflammatory phase, Agilegel promotes the polarization of macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype using IL-10. Subsequently, Agilegel stimulates cell proliferation, angiogenesis, and extracellular matrix formation through the action of VEGF-α, thereby accelerating the closure of DW. Our results indicate that DNA hydrogels confer the capacity to regulate the sequential release of drugs, enabling them to effectively manage the phased intervention of multiple drugs in the treatment of complex diseases within physiological environments.

An in-Situ Study of the Transformation of Hybrid Layered Hydroxides into Metallic Nanocomposites with Interest in Energy Storage Systems

The high increase of energy demand in recent decade and the necessity of reduce the fossil fuel consumption have triggered the interest of the scientific community in the search of 'green' alternatives. Due to the characteristic intermittence of solar and wind technologies, there is a huge effort on the development energy storage systems. Among them hybrid capacitors (HCs) are promising systems due its high energy and power density values, in comparison with Li-ion batteries, that make them ideal for industrial and automobile applications. Battery-like materials such as nanocomposites (NCs) based on metallic nanoparticles (working as pseudo-capacitor based in redox reactions) with a carbon matrix (working as electric double layer capacitors) are key HCs systems itself. These NCs exhibits a notorious enhancement on their electrochemical performance by applying an external magnetic field. [1] Typically, NCs are obtained by the thermal decomposition of hybrid materials under inert atmosphere, as it has been demonstrated for the case of layered double hydroxides (LDHs), layered hydroxides (α-LHs) and metal organic frameworks (MOFs). [1-3] However, there is a lack of information in terms how the thermal transformation takes places.In this work, we present for the first-time an in-situ study about the transformation of hybrid layered hydroxides into NCs. For that, synchrotron measurements of X-ray absorption spectroscopy (XAS) and powder X-ray diffraction (PXRD) are performed for different hybrid layered hydroxides to follow the transformation in terms of oxidation state and crystallinity. These hybrid layered hydroxides will variate on: (i) the layered hydroxide structure and the anion-layer interactions (LDHs vs α-LHs + electrostatic vs covalent), (ii) the cation nature, and (iii) the identity of the organic linkers, to name a few. For instance, in the case of α-LHs, while the LHs structure defines the thermal decomposition, and the organic molecule length controls the quality and quantity of the final carbon matrix at the NCs.[4] Interestingly, in function of the amount of carbon present on the organic molecule, the oxidation state and the formation of the carbon matrix on the final material are conditioned, which imply that there is a minimum amount of carbon to obtain the NCs. In the other hand, for the previous NCs obtained, the electrochemical characterization is performed in pouch cells, applying an external magnetic field throughout the galvanostatic cycles. This assembly prevents the loss of material along the time and during the process, where it is evidenced how the magnetic field improves the electrochemical performance with an increase in the specific capacity of the NCs. In overall, this work introduces fundamental knowledge on the rational design of hybrid layered hydroxides and the subsequent nanocomposites and its performance in energy storage systems.

Recycling of PFSA-Based Membranes and Their Re-Application in PEM Fuel Cells

The commercialization of PEM fuel cells offers a promising opportunity to overcome our dependence on fossil fuels and provides an attractive alternative for automotive and stationary power applications.[1] However, PEMFCs are still costly in production, with the main cost factor due to the fabrication of the perfluorosulfonic acid (PFSA)-based proton exchange membrane and the noble metal catalysts.[2,3] Recycling of these components could increase the economic attractiveness of PEMFCs. However, while the high resistance of the ionomer membrane to thermal and chemical degradation is favorable for their use in fuel cells, it also makes membrane recycling a major challenge.Here, we present a newly developed recycling strategy to recover PFSA-based membranes after operation by a hydrothermal treatment. Both short side chain (SSC) and long side chain (LSC) ionomers with EWs of 800 and 1000 were investigated. In contrast to previously published methods, we were able to recover the PFSA ionomer by using water instead of high-boiling organic solvents, such as DMF or DMSO.[4,5] The recycled membranes were obtained from the recycled PFSA ionomer solution by doctor-blading. They were investigated by in-situ Raman techniques for studying the water uptake and analyzed by IR and small-angle X-ray scattering (SAXS) techniques to get a more detailed insight into their morphology. In single cell tests at standard (80 °C) and enhanced (up to 130 °C) PEMFC operating temperatures, the recycled membranes showed an increased cell performance as compared to the pristine 3M-800EW membrane. Solid-state NMR measurements confirmed that no chemical changes in the membrane occurred due to the heat-treatment process.We assume that the observed performance boost can be attributed to an increased water uptake and retention. Furthermore, a change in the polymer matrix formation may be responsible for the observed behavior, which led to an expanded water filled channel structure, where water can accumulate to facilitate proton diffusion as H3O+ through the channels. To confirm this assumption, the morphology of the recycled membranes will be investigated by in situ SAXS measurements at different temperatures and degrees of hydration.[1] I. Staffell, D. Scamman, A. Velazquez Abad, P. Balcombe, P. E. Dodds, P. Ekins, N. Shah, K. R. Ward, Energy Environ. Sci. 2019, 12, 463–491.[2] J. Fan, M. Chen, Z. Zhao, Z. Zhang, S. Ye, S. Xu, H. Wang, H. Li, Nat. Energy 2021, 6, 475–486.[3] D. Papageorgopoulos, Fuel Cell R&D Overview. 2019 Annual Merit Review and Peer Evaluation Meeting, 2019.[4] Q. Xu, X. Chen, S. Wang, C. Guo, Y. Niu, R. Zuo, Z. Yang, Y. Zhou, C. Xu, Energies 2022, 15, 8717.[5] H. F. Xu, X. Wang, Z. G. Shao, I. M. Hsing, J. Appl. Electrochem. 2002, 32, 1337–1340.

Polymer Tablet Matrix Systems for the Controlled Release of Dry Betula pendula Leaf Extract.

The aim of the study was to develop polymer matrix tablets with modified release of dry Betula pendula leaf extract and to investigate basic parameters influencing the drug release pattern. To fully assess the statistical significance of the influence of the individual factors in the tablet formulation development as well as the combination of them, Tukey's tests and a complete 33 factor analysis of variance (ANOVA) were applied. The following three factors were studied at three levels (low, medium and high): influence of the hydrophobic/hydrophilic polymer ratio Ethylcellulose (EC)/Hydroxypropyl methylcellulose (HPMC) (40/60, 25/75 and 10/90), influence of HPMC molecular weight (500 kDa, 750 kDa and 1150 kDa), and influence of the compression force applied (1 t, 1.5 t and 2 t). The effect of these varied parameters on the drug release parameter t80 was evaluated statistically. Twenty-seven tablet models were formulated, including all possible combinations of the variables. The obtained drug release profiles demonstrated that a 25/75 (EC/HPMC) ratio was the most suitable for prolonging the release process. Increasing the molecular weight of HMPC from 500 kDa to 750-1150 kDa and applying higher compression force significantly influenced the studied t80 values and caused sustained drug release (t80 up to 7.97 h). The combination of the hydrophilic HPMC polymer with the hydrophobic EC can result in the formation of a promising drug-carrying matrix, offering effective control of the drug release process.

Cyclic strain of poly (methyl methacrylate) surfaces triggered the pathogenicity of Candida albicans

Candida albicans is an opportunistic yeast and the primary etiological factor in oral candidiasis and denture stomatitis. The pathogenesis of C. albicans could be triggered by several variables, including environmental, nutritional, and biomaterial surface cues. Specifically, biomaterial interactions are driven by different surface properties, including wettability, stiffness, and roughness. Dental biomaterials experience repetitive (cyclic) stresses from chewing and biomechanical movements. Pathogenic biofilms are formed over these biomaterial surfaces under cyclic strain. This study investigated the effect of the cyclic strain (deformation) of biomaterial surfaces on the virulence of Candida albicans. Candida biofilms were grown over Poly (methyl methacrylate) (PMMA) surfaces subjected to static (no strain) and cyclic strain with different levels (ε˜x=0.1 and 0.2%). To evaluate the biomaterial-biofilm interactions, the biofilm characteristics, yeast-to-hyphae transition, and the expression of virulent genes were measured. Results showed the biofilm biomass and metabolic activity to be significantly higher when Candida adhered to surfaces subjected to cyclic strain compared to static surfaces. Examination of the yeast-to-hyphae transition showed pseudo-hyphae cells (pathogenic) in cyclically strained biomaterial surfaces, whereas static surfaces showed spherical yeast cells (commensal). RNA sequencing was used to determine and compare the transcriptome profiles of cyclically strained and static surfaces. Genes and transcription factors associated with cell adhesion (CSH1, PGA10, and RBT5), biofilm formation (EFG1), and secretion of extracellular matrix (ECM) (CRH1, ADH5, GCA1, and GCA2) were significantly upregulated in the cyclically strained biomaterial surfaces compared to static ones. Genes and transcription factors associated with virulence (UME6 and HGC1) and the secretion of extracellular enzymes (LIP, PLB, and SAP families) were also significantly upregulated in the cyclically strained biomaterial surfaces compared to static. For the first time, this study reveals a biomaterial surface factor triggering the pathogenesis of Candida albicans, which is essential for understanding, controlling, and preventing oral infections. Statement of significanceFungal infections produced by Candida albicans are a significant contributor to various health conditions. Candida becomes pathogenic when certain environmental conditions change, including temperature, pH, nutrients, and CO2 levels. In addition, surface properties, including wettability, stiffness, and roughness, drive the interactions between Candida and biomaterials. Clinically, Candida adheres to biomaterials that are under repetitive deformation due to body movements. In this work, we revealed that when Candida adhered to biomaterial surfaces subjected to repetitive deformation, the microorganism becomes pathogenic by increasing the formation of biofilms and the expression of virulent factors related to hyphae formation and secretion of enzymes. Findings from this work could aid the development of new strategies for treating fungal infections in medical devices or implanted biomaterials.

Fine study of hierarchical interphase constructed by Ti3SiC2 and carbon nanotubes in SiCf/SiC composites

The interphase in silicon carbide fiber-reinforced silicon carbide ceramic matrix composites (SiCf/SiC) assumes a significant role in the mechanical properties exhibited at elevated temperatures. The strength, toughness, and chemical stability of a composite is frequently influenced by the optimization of its interphase. In this work, the MAX phase (Ti3SiC2) and carbon nanotubes (CNTs) were successively deposited on the SiCf using the molten salt method and chemical vapor deposition technique, respectively, to create a hierarchical structure. Transmission electron microscopy was employed to undertake a comprehensive investigation of the interfacial component in SiCf/SiC composites. The detailed study of interphases in SiCf/SiC composites has been conducted through the analysis of crystallization, the bonding natures, and the micromorphology, encompassing geometry and constituent characteristics. A bilayer consisting of TiC–Ti3SiC2/Ti5Si3 and a vertical array of carbon nanotubes (CNTs) with a length of 7 μm is fabricated on the surface of SiCf/Ti3SiC2-CNTs. The SiCf/Ti3SiC2/SiC and SiCf/Ti3SiC2-CNTs/SiC composites exhibit lamellar structures of Ti3SiC2, which indicates a further crystallization of Ti3SiC2 resulting from the formation of SiC matrix by PIP procedure. The interphase of SiCf/Ti3SiC2-CNTs/SiC composite may be categorized into four distinct layers: a TiC phase, a TiSi2 phase, a transition phase of TiSi2/TiC, and a Ti3SiC2 phase. This interphase structure is more intricate compared to the interphase structure observed in the SiCf/Ti3SiC2/SiC composite. This research indicates significant value for the future design and optimization of interfaces.

Physicochemical Fundamentals of the Synthesis of a Cu@BN Composite Consisting of Nanosized Copper Enclosed in a Boron Nitride Matrix

The thermal reduction of the copper(II) complexes [CuII(N2H4)3][B10H10]·nH2O (I·nH2O) and [CuII(NH3)4][B10H10]·nH2O (II·nH2O) has been studied in an argon atmosphere at 900 °C. It has been found that the annealing of both compounds results in a Cu@BN boron-containing copper composite. It has been shown that this process leads to the formation of a boron nitride matrix doped with cubic copper(0) nanoparticles due to the copper(II)→copper(I)→copper(0) thermal reduction. The phase composition of annealing products I900 and II900 has been determined based on powder X-ray diffraction, IR spectroscopy and thermal analysis data. The morphology, average particle size and composition of the composite have been determined by TEM and high-resolution TEM + EDS. The average particle size has been found to be about 81 nm and 52 nm for samples I900 and II900, respectively. Comparison of the results obtained using physicochemical studies has shown the identity of the composition of the products of annealing I900 and II900. The electrical properties of a coating based on an I900 sample modified with Cu0→Cu2O in situ during deposition on a chip at 300 °C in air have been studied. As a result, with increasing temperature, an increase in the electrical conductivity characteristic of semiconductors has been observed.

Substrate and arrhythmia characterization using the multi-electrode Optrell mapping catheter for ventricular arrhythmia ablation-a single-center experience.

The use of a multi-electrode Optrell mapping catheter during ventricular tachycardia (VT) or premature ventricular complex (PVC) ablation procedures has not been widely reported. We aim to describe the feasibility and safety of using the Optrell multipolar mapping catheter (MPMC) to guide catheter ablation of VT and PVCs. We conducted a single-center, retrospective evaluation of patients who underwent VT or PVC ablation between June and November 2022 utilizing the MPMC. A total of 20 patients met the inclusion criteria (13 VT and 7 PVC ablations, 80% male, 61 ± 15years). High-density mapping was performed in the VT procedures with median 2753 points [IQR 1471-17,024] collected in the endocardium and 12,830 points [IQR 2319-30,010] in the epicardium. Operators noted challenges in manipulation of the MPMC in trabeculated endocardial regions or near valve apparatus. Late potentials (LPs) were detected in 11 cases, 7 of which had evidence of isochronal crowding demonstrated during late annotation mapping. Two patients who also underwent entrainment mapping had critical circuitry confirmed in regions of isochronal crowding. In the PVC group, high-density voltage and activation mapping was performed with a median 1058 points [IQR 534-3582] collected in the endocardium. This novel MPMC can be used safely and effectively to create high-density maps in LV endocardium or epicardium. Limitations of the catheter include a longer wait time for matrix formation prior to starting point collection and challenges in manipulation in certain regions.

Increased Levels of BAMBI Inhibit Canonical TGF-β Signaling in Chronic Wound Tissues.

Chronic wounds affect more than 2% of the population worldwide, with a significant burden on affected individuals, healthcare systems, and societies. A key regulator of the entire wound healing cascade is transforming growth factor beta (TGF-β), which regulates not only inflammation and extracellular matrix formation but also revascularization. This present work aimed at characterizing wound tissues obtained from acute and chronic wounds regarding angiogenesis, inflammation, as well as ECM formation and degradation, to identify common disturbances in the healing process. Serum and wound tissues from 38 patients (N = 20 acute and N = 18 chronic wounds) were analyzed. The patients' sera suggested a shift from VEGF/VEGFR to ANGPT/TIE2 signaling in the chronic wounds. However, this shift was not confirmed in the wound tissues. Instead, the chronic wound tissues showed increased levels of MMP9, a known activator of TGF-β. However, regulation of TGF-β target genes, such as CTGF, COL1A1, or IL-6, was absent in the chronic wounds. In wound tissues, all three TGF-β isoforms were expressed with increased levels of TGF-β1 and TGF-β3 and a reporter assay confirmed that the expressed TGF-β was activated. However, Western blots and immunostaining showed decreased canonical TGF-β signaling in the respective chronic wound tissues, suggesting the presence of a TGF-β inhibitor. As a potential regulatory mechanism, the TGF-β proteome profiler array suggested elevated levels of the TGF-β pseudo-receptor BAMBI. Also, tissue expression of BAMBI was significantly increased not only in chronic wounds (10.6-fold) but also in acute wounds that had become chronic (9.5-fold). In summary, our data indicate a possible regulatory role of BAMBI in the development of chronic wounds. The available few in vivo studies support our findings by postulating a therapeutic potential of BAMBI for controlling scar formation.

How a Game Theoretic Approach Can Minimize the Cost of Train Passenger Services: An Intermodal Competition between Rail and Road Transport

Game theory models provide very powerful tools for evaluating strategies that are beneficial to both rail and road operators competing for passengers on parallel routes. This study examines how game theory can help rail operators who are incurring losses on passenger transport to identify strategies that can minimise costs, using the methodology of dual linear programming to analyse strategies. In identifying the best strategies for minimising costs for the railway operator, the best strategies for maximising profits for the road operators are also identified. The game model is set up between two passenger transport operators (rail and road) and is based on the income earned by the road operators from passengers. This study illustrates the following: how the strategies of the two competitors (rail and road) are determined; the formation of the payoff matrix and the presentation of the mathematical problem for the two competitors; and the results and verification of the best strategies for both competitors. The Leonid Hurwicz criterion was used to verify the optimal strategies.

Chlorinated-based bioceramics incorporated in polycaprolactone membranes.

The development of bioactive membranes with bone repair properties is great interest in the field of tissue engineering. In this study, we aimed to fabricate and characterize a composite membrane composed of sol-gel synthesized bioceramics and electrospun polycaprolactone (PCL) fibers for bone tissue regeneration applications. The bioceramics were prepared using the sol-gel method with nitrate (N) and chloride (CL) as precursors. PCL and bioceramic solutions were electrospun to obtain ultrafine fiber mats. Raman spectroscopy, x-ray diffraction (XRD), Fourier Transform Infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM) were used to characterize the materials. The results showed that both chlorinated and non-chlorinated bioceramics contained NBOs (non-bridge bonds) and crystallized the α-wollastonite phase, with the chlorinated version doing so at lower temperatures. In vitro tests were performed to evaluate cytotoxicity, cell adhesion, and mineralized matrix formation on the membranes. The composite membranes showed improved cell viability and promoted mineralization nodules formation. This study presents a promising approach for the development of bioactive membranes for bone tissue engineering, with potential applications in bone regeneration therapies.

LncRNA H19-EZH2 interaction promotes liver fibrosis via reprogramming H3K27me3 profiles.

Liver fibrosis is a wound-healing process characterized by excess formation of extracellular matrix (ECM) from activated hepatic stellate cells (HSCs). Previous studies show that both EZH2, an epigenetic regulator that catalyzes lysine 27 trimethylation on histone 3 (H3K27me3), and long non-coding RNA H19 are highly correlated with fibrogenesis. In the current study, we investigated the underlying mechanisms. Various models of liver fibrosis including Mdr2-/-, bile duct ligation (BDL) and CCl4 mice were adapted. We found that EZH2 was markedly upregulated and correlated with H19 and fibrotic markers expression in these models. Administration of EZH2 inhibitor 3-DZNeP caused significant protective effects in these models. Furthermore, treatment with 3-DZNeP or GSK126 significantly inhibited primary HSC activation and proliferation in TGF-β-treated HSCs and H19-overexpreesing LX2 cells in vivo. Using RNA-pull down assay combined with RNA immunoprecipitation, we demonstrated that H19 could directly bind to EZH2. Integrated analysis of RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) further revealed that H19 regulated the reprogramming of EZH2-mediated H3K27me3 profiles, which epigenetically promoted several pathways favoring HSCs activation and proliferation, including epithelial-mesenchymal transition and Wnt/β-catenin signaling. In conclusion, highly expressed H19 in chronic liver diseases promotes fibrogenesis by reprogramming EZH2-mediated epigenetic regulation of HSCs activation. Targeting the H19-EZH2 interaction may serve as a novel therapeutic approach for liver fibrosis.

M1/M2 Macrophage Skewing is Related to Reduction in Types I, V, and VI Collagens with Aging in Sun-Exposed Human Skin

Sun-exposed, aged human skin is fragile because of collagen fragmentation and loss. We recently reported that the balance of M1 and M2 macrophages is associated with chronic inflammation and related inflammaging in sun-exposed human skin. In this study, we analyzed its role in the maintenance of collagen matrix formation by performing histological analyses of human facial skin. In addition, RNA sequencing, protein assays, and functional assays revealed the details of the mechanism. The number of M2 macrophages was positively correlated with the abundance of type I collagen, whereas the M1/M2 ratio was negatively correlated with the abundance of type V and VI collagen, which are the essential minor collagens required for collagen assembly in the skin; however, there was no correlation with type III collagen. Furthermore, M2 macrophages induced the expression of the proteins required for the assembly of collagen fibrils, suggesting that the M1/M2 balance controls not only the quantity but also the quality of the collagen matrix. Indeed, M1 macrophages induced abnormal collagen fibrils consisting of types I, V, and VI collagens. Our results demonstrate the relationship between the M1/M2 balance and the dysregulation of collagen homeostasis in photoaged skin and suggest the possible involvement of macrophages in skin photoaging.

Investigation of the wear resistance of in-situ Al-Ti composites fabricated by mechanical alloying and hot extrusion

ABSTRACT In this research, the wear behaviour of Al-20%Ti composites, fabricated by mechanical alloying and hot extrusion at different conditions, was investigated using the pin-on-disc method. A high-energy vibratory mill was applied to produce the nanocomposite (Al-20Ti-4hrV) and nanocrystalline (NC) Al samples, while a low-energy planetary mill was used to produce the other composites (Al-20Ti-20hrP and Al-20Ti-60hrP). To examine the microstructure and worn surface of specimens, optical microscopy and scanning electron microscopy were performed. To estimate the mechanical properties of the samples, their density and Brinell hardness were measured. The use of a high-energy vibratory mill caused the formation of an ultrafine aluminium matrix with in-situ nanometric intermetallic particles in the Al-20Ti-4hrV sample. As a result, the highest relative density and hardness and the best wear resistance were obtained in the Al-20Ti-4hrV sample. The application of the low-energy planetary mill led to the formation of flaky particles; accordingly, low relative density, poor mechanical properties and wear resistance in Al-20Ti-20hrP and Al-20Ti-60hrP samples were observed. The dominant wear mechanisms for Al-20Ti-4hrV and NC Al samples were identified as microploughing, adhesion and oxidation in the mild wear regime, whereas those of the Al-20Ti-20hrP and Al-20Ti-60hrP samples were mainly adhesion wear mechanism and inconsiderable delamination in the mild wear regime. The highest hardness and wear resistance were obtained for the nanocomposite sample owing to nanometric Al3Ti reinforcement, nanocrystalline Al matrix and good adhesion between particles and the matrix. This study confirmed that the nanocomposite production method presented in this research is suitable for wear-resistance applications.

TNF-α, IL-1B and IL-6 affect the differentiation ability of dental pulp stem cells

BackgroundThis in vitro study examined the effect of the inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6) on osteogenic, chondrogenic, and adipogenic differentiation of dental pulp stem cells (DPSCs) which have significant relevance in future regenerative therapies.MethodsDPSCs were isolated from the impacted third molar dental pulp and determined with flow cytometry analysis. DPSCs were divided into into 5 main groups with 3 subdivisions for each group making a total of 15 groups. Experimental groups were stimulated with TNF-α, IL-1β, IL-6, and a combination of all three to undergo osteogenic, chondrogenic, and adipogenic differentiation protocols. Next, the differentiation of each group was examined with different staining procedures under a light microscope. Histological analysis of osteogenic, chondrogenic, and adipogenic differentiated pellets was assessed using a modified Bern score. Statistical significance determined using one-way analysis of variance, and correlations were assessed using Pearson’s test (two-tailed).ResultsStimulation with inflammatory cytokines significantly inhibited the osteogenic, chondrogenic and adipogenic differentiation of DPSCs in terms of matrix and cell formation resulting in weak staining than the unstimulated groups with inflammatory cytokines. On contrary, the unstimulated groups of MSCs have shown to be highly proliferative ability in terms of osteogenic, chondrogenic, and adipogenic differentiation.ConclusionsDPSCs have high osteogenic, chondrogenic, and adipogenic differentiation capabilities. Pretreatment with inflammatory cytokines decreases the differentiation ability in vitro, thus inhibiting tissue formation.

Diatom adhesive trail proteins acquired by horizontal gene transfer from bacteria serve as primers for marine biofilm formation.

Biofilm-forming benthic diatoms are key primary producers in coastal habitats, where they frequently dominate sunlit intertidal substrata. The development of gliding motility in raphid diatoms was a key molecular adaptation that contributed to their evolutionary success. However, the structure-function correlation between diatom adhesives utilized for gliding and their relationship to the extracellular matrix that constitutes the diatom biofilm is unknown. Here, we have used proteomics, immunolocalization, comparative genomics, phylogenetics and structural homology analysis to investigate the evolutionary history and function of diatom adhesive proteins. Our study identified eight proteins from the adhesive trails of Craspedostauros australis, of which four form a new protein family called Trailins that contain an enigmatic Choice-of-Anchor A (CAA) domain, which was acquired through horizontal gene transfer from bacteria. Notably, the CAA-domain shares a striking structural similarity with one of the most widespread domains found in ice-binding proteins (IPR021884). Our work offers new insights into the molecular basis for diatom biofilm formation, shedding light on the function and evolution of diatom adhesive proteins. This discovery suggests that there is a transition in the composition of biomolecules required for initial surface colonization and those utilized for 3D biofilm matrix formation.

In situ tailoring of Ag-doped-TiO2/TPMP/cotton nanocomposite with UV-protective, self-sterilizing and flame-retardant performance for advanced technical textiles

Herein, we present a novel approach to the development of a multifunctional, UV-protective, photocatalytic, antimicrobial and flame-retardant nanocomposite fabric surface. Using a sol–gel/hydrothermal approach, a phosphorus-based flame-retardant 3-(trihydroxysilyl)propyl methylphosphonate (TPMP) in combination with Ag-doped TiO2 was applied to the surface of cotton fibers for the first time, using an aqueous AgNO3 solution as the dopant. The modified cotton fabrics were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy-dispersive X-ray analysis (EDS) and X-ray diffraction spectroscopy (XRD) to confirm the successful application of Ag-TiO2 and TPMP on the cotton fabric by analyzing the surface morphology, chemical composition, chemical bonding and crystal structure. The functional properties of the modified cotton fabric were determined by measuring the UV protection factor (UPF), burning behavior and thermo-oxidative stability, as well as antibacterial activity against Escherichia coli and Staphylococcus aureus. The results show the formation of a unique nanocomposite matrix of TPMP–polysiloxane on the surface of cotton fibers with well-distributed Ag-TiO2. The formation of TiO2/Ag2O particles on the surface of cellulose fibers was also confirmed. The synergism between all components of the nanocomposite resulted in excellent UV protection in the UVA and UVB region, with a UPF of 50+, self-sterilizing activity against both tested bacteria and enhanced thermo-oxidative stability. Therefore, the novel approach proposed herein is promising for the development of multifunctional, protective surfaces for advanced technical textiles.

Exploration of advanced computer technology to address analytical and noise improvement issues in machine learning

Computer-based visual recognition technology combined with deep learning enables accurate image matching through interactive, multi-level comparison. Currently, popular search methods such as RNN, Faster RNN, etc. are used in computer vision to compute image information by performing hierarchical comparison of image objects. In today’s machine learning is used to construct training curves to predict corresponding results, but the accuracy rate will cause some data distortion due to overformation. Therefore, to solve the problem of interference is now physical, the abandonment method is developed to extract certain neurons and reduce the number of feature values. In this study, a visual image recognition framework is designed that uses advanced computer technology to mark and compare images, and to mark and eliminate blurred images. The experimental method successfully improves the prediction of accuracy after a judgment error by comparing the results of training with the results of deep learning verification. The accuracy of matrix formation and result prediction can reach 0.9812 without eliminating the image produced by the light-emitting elements. We remove noisy images based on the same sampling information. After re-training and re-predicting, the accuracy can reach 0.9847.