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.Interfacial separation of soft, often viscoelastic, materials typically cause the onset of instabilities, such as cavitation and fingering. These instabilities complicate the pathways for interfacial separation, and hence hinder the quantitative characterization of bulk and interfacial contributions to soft material adhesion. To overcome these challenges, we developed a method termed pressurized interfacial failure (PIF), in which the interfacial separation is controlled by applying a positive pressure at the contact interface between a rigid, annular probe and a thin adhesive. We conducted experiments on model and commercially-available acrylic adhesives. Surprisingly, all the materials studied here fail by an inside-out growth of an interfacial cavity and show similar trends in the interrelationship between the cavity radius, applied pressure and change of contact force. In contrast, the force-displacement relationships of the same materials measured by conventional tack tests vary significantly. Accordingly, we conclude that the PIF method allows for controlling the interfacial failure mechanism. Furthermore, we have applied a linear elastic fracture mechanics framework and conducted finite element analysis to develop analytical models to calculate the critical energy release rate for interfacial separation, Gc. For model acrylic adhesives and commercially available adhesives, the values of Gc are similar to values determined by sphere-probe tack tests. Collectively, the herein introduced PIF method and analysis work provide a new foundation for quantitatively decoupling the interfacial and bulk contributions to soft polymer adhesion.To mimic biological tissues with high toughness such as cartilage, it is highly desired to fabricate stable and tough hydrogels with intricate shapes to act as a structural support. Extrusion-based 3D printing is a promising method to fabricate 3D scaffolds with various architectures; however, printing tough hydrogel structures with high fidelity and resolution is still a challenge. In this work, we adopt the fast sol-to-gel transition of κ-carrageenan in the solution of acrylamide upon cooling to fix the printed scaffolds and polymerize the precursor solution to form the second network. read more The printed constructs of κ-carrageenan/polyacrylamide double-network gels are toughened by soaking in an aqueous solution of zirconyl chloride to form coordination complexes between the Zr4+ ions and sulfate groups of κ-carrageenan. The obtained hydrogels are stable in water and possess good mechanical properties, with a tensile breaking stress of 1-2 MPa, breaking strain of 100-150%, and Young's modulus of 4-10 MPa. The printed grid can hold 150 times its own weight. link2 3D printed constructs with a high aspect ratio and shape fidelity are obtained by optimizing the printing parameters. Furthermore, a biomimetic strategy is applied to construct a hydrogel composite by filling the printed tough hydrogel scaffold with a cell-laden fibrin hydrogel as the soft substance. Chondrocytes in the hydrogel composite maintain high viability after cyclic compression, demonstrating the load-bearing capacity of the tough scaffold and favorable microenvironment for cells provided by the embedded soft fibrin gel. We envision that this printing strategy for hydrogel constructs with high toughness and good stability, as well as the method to form tough-soft hydrogel composites, can be extended to other systems to develop structural elements and scaffolds towards applications in biomedical devices and tissue engineering.Bacterial infections and antibiotic resistance have become a global healthcare crisis. Herein, we designed and synthesized a series of cationic amphiphilic dendrons with cationic dendrons and hydrophobic alkyl chains for potential antibacterial applications. Our results showed that the antimicrobial activities of the cationic amphiphilic dendrons were highly dependent upon the length of the hydrophobic alkyl chain, whereas the number of cationic charges was less important. Among these cationic amphiphilic dendrons, a prime candidate was identified, which possessed excellent antimicrobial activity against various pathogens (minimum inhibitory concentrations of 9, 3, and 3 μg mL-1 for Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus, respectively). Scanning electron microscopy and fluorescence microscopy analyses showed that it could disrupt the integrity of a pathogen's membrane, leading to cell lysis and death. In addition, in vitro bacteria-killing kinetics showed that it had rapid bactericidal efficiency. It also had excellent antimicrobial activities against MRSA in vivo and promoted wound healing. In general, the synthesized cationic amphiphilic dendrons, which exhibited rapid and broad-spectrum bactericidal activity, may have great potential in antimicrobial applications.Atherosclerosis is a global disease with an extremely high morbidity and fatality rate, so it is necessary to develop effective treatments to reduce its impact. In this work, we successfully prepared a multifunctional drug-loaded nano-delivery system with pH-responsive, CD44-targeted, and chemical-photothermal synergistic treatment. Dendritic mesoporous silica nanoparticles capped with copper sulfide (CuS) were synthesized via an oil-water biphase stratification reaction system; these served as the carrier material and encapsulated the anticoagulant drug heparin (Hep). The pH-sensitive Schiff base bond was used as a gatekeeper and targeting agent to modify hyaluronic acid (HA) on the surface of the nanocarrier. HA coating endowed the nanocomposite with the ability to respond to pH and target CD44-positive inflammatory macrophages. Based on this multifunctional nanocomposite, we achieved precise drug delivery, controlled drug release, and chemical-photothermal synergistic treatment of atherosclerosis. The in vitro drug release results showed that the nanocarriers exhibited excellent drug-controlled release properties, and could release drugs in the weakly acidic microenvironment of atherosclerotic inflammation. Cytotoxicity and cell uptake experiments indicated that nanocarriers had low cytotoxicity against RAW 264.7 cells. Modification of HA to nanocarriers can be effectively internalized by RAW 264.7 cells stimulated by lipopolysaccharide (LPS). Combining CuS photothermal treatment with anti-atherosclerosis chemotherapy showed better effects than single treatment in vitro and in vivo. In summary, our research proved that H-CuS@DMSN-NC-HA has broad application prospects in anti-atherosclerosis.Since the degree of particle dispersion can determine the physical properties of polymer nanocomposites (PNCs), plenty of studies have focused on the intrinsic parameters of PNCs such as the concentration/size/chemistry of nanoparticles/polymers relevant to the particle microstructure. While the consideration of these parameters is based on PNCs being in their equilibrium states, PNCs can be kinetically trapped in a nonequilibrium state during the multiple steps of processing. In other words, processing conditions can contribute more significantly to particle dispersion and the properties of PNCs beyond the effects of the intrinsic parameters. Hence, a systematic understanding of the nonequilibrium behaviour of PNCs is required to achieve the desired properties. In this work, we prepared concentrated suspensions with two different preparation pathways. The two different pathways yield different polymer conformations particularly near the particle surface despite the same composition of particles/polymers as the systems are trapped in a nonequilibrium state. Accordingly, the particle microstructures are also greatly changed by the preparation pathway. We found that even in the presence of solvents, these preparation pathway-dependent nonequilibrium effects on particle microstructures persist after several months of aging and ultimately determine the long-term stability of the particle dispersion.The increasing threat of nuclear terrorism or radiological accident has made high throughput radiation biodosimetry a requisite for the immediate response for triage. Owing to detection of subtle alterations in biological pathways before the onset of clinical conditions, metabolomics has become an important tool for studying biomarkers and the related mechanisms for radiation induced damage. link3 Here, we have attempted to combine two detection techniques, LC-MS and 1H NMR spectroscopy, to obtain a comprehensive metabolite profile of urine at 24 h following lethal (7.5 Gy) and sub-lethal (5 Gy) irradiation in mice. Integrated data analytics using multiblock-OPLSDA (MB-OPLSDA), correlation networking and pathway analysis was used to identify metabolic disturbances associated with radiation exposure. MB-OPLSDA revealed better clustering and separation of irradiated groups compared with controls without overfitting (p-value of CV-ANOVA 1.5 × 10-3). Metabolites identified through MB-OPLSDA, namely, taurine, creatine, citrate and 2-oxoglutarate, were found to be dose independent markers and further support and validate our earlier findings as potential radiation injury biomarkers. Integrated analysis resulted in the enhanced coverage of metabolites and better correlation networking in energy, taurine, gut flora, L-carnitine and nucleotide metabolism observed post irradiation in urine. Our study thus emphasizes the major advantage of using the two detection techniques along with integrated analysis for better detection and comprehensive understanding of disturbed metabolites in biological pathways.Radial superlattices are nanostructured materials obtained by rolling up thin solid films into spiral-like tubular structures. The formation of these "high-order" superlattices from two-dimensional crystals or ultrathin films is expected to result in a transition of transport characteristics from two-dimensional to one-dimensional. Here, we show that a transport hallmark of radial superlattices is the appearance of magnetoconductance modulations in the presence of externally applied axial magnetic fields. This phenomenon critically relies on electronic interlayer tunneling processes that activate an unconventional Aharonov-Bohm-like effect. Using a combination of density functional theory calculations and low-energy continuum models, we determine the electronic states of a paradigmatic single-material radial superlattice - a two-winding carbon nanoscroll - and indeed show momentum-dependent oscillations of the magnetic states in the axial configuration, which we demonstrate to be entirely due to hopping between the two windings of the spiral-shaped scroll.MELAS (mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes) is a progressive neurodegenerative disease caused by pathogenic mitochondrial DNA variants. The pathogenic mechanism of MELAS remains enigmatic due to the exceptional clinical heterogeneity and the obscure genotype-phenotype correlation among MELAS patients. To gain insights into the pathogenic signature of MELAS, we designed a comprehensive strategy integrating proteomics and metabolomics in patient-derived dermal fibroblasts harboring the ultra-rare MELAS pathogenic variant m.14453G>A, specifically affecting the mitochondrial respiratory complex I. Global proteomics was achieved by data-dependent acquisition (DDA) and verified by data-independent acquisition (DIA) using both Spectronaut and the recently launched MaxDIA platforms. Comprehensive metabolite coverage was achieved for both polar and nonpolar metabolites in both reverse phase and HILIC LC-MS/MS analyses. Our proof-of-principle MELAS study with multi-omics integration revealed OXPHOS dysregulation with a predominant deficiency of complex I subunits, as well as alterations in key bioenergetic pathways, glycolysis, tricarboxylic acid cycle, and fatty acid β-oxidation.
Read More: https://www.selleckchem.com/products/pf-06424439.html
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