A Biologically Muscle-Inspired Polyurethane with Super-Tough,Thermal Reparable and Self-Healing Capabilities for Stretchable Electronics

Polymeric elastomers play an increasingly important role in the development of stretchable electronics. A highly demanded elastic matrix is preferred to own not only excellent mechanical properties, but also additional features like high toughness and fast self-healing. Here, a polyurethane (DA-PU) is synthesized with donor and acceptor groups alternately distributed along the main chain to achieve both intra-chain and inter-chain donor-acceptor self-assembly, which endow the polyurethane with toughness, self-healing, and, more interestingly, thermal repair, like human muscle. In detail, DA-PU exhibits an amazing mechanical performance with elongation at break of 1900% and toughness of 175.9 MJ m⁻³. Moreover, it shows remarkable anti-fatigue and anti-stress relaxation properties as manifested by cyclic tensile and stress relaxation tests, respectively. Even in case of large strain deformation or long-time stretch, it can almost completely restore to original length by thermal repair at 60 °C in 60 s. The self-healing speed of DA-PU is gradually enhanced with the increasing temperature, and can be 1.0–6.15 µm min⁻¹ from 60 to 80 °C. At last, a stretchable and self-healable capacitive sensor is constructed and evaluated to prove that DA-PU matrix can ensure the stability of electronics even after critical deformation and cut off.     

Translesion Synthesis or Repair by Specialized DNA Polymerases Limits Excessive Genomic Instability upon Replication Stress

DNA can experience “replication stress”, an important source of genome instability, induced by various external or endogenous impediments that slow down or stall DNA synthesis. While genome instability is largely documented to favor both tumor formation and heterogeneity, as well as drug resistance, conversely, excessive instability appears to suppress tumorigenesis and is associated with improved prognosis. These findings support the view that karyotypic diversity, necessary to adapt to selective pressures, may be limited in tumors so as to reduce the risk of excessive instability. This review aims to highlight the contribution of specialized DNA polymerases in limiting extreme genetic instability by allowing DNA replication to occur even in the presence of DNA damage, to either avoid broken forks or favor their repair after collapse. These mechanisms and their key regulators Rad18 and Polθ not only offer diversity and evolutionary advantage by increasing mutagenic events, but also provide cancer cells with a way to escape anti-cancer therapies that target replication forks.     

Engineering Bioactive M2 Macrophage-Polarized Anti-Inflammatory,Antioxidant, and Antibacterial Scaffolds for Rapid Angiogenesis and Diabetic Wound Repair

Diabetic wound healing still faces great challenges due to the excessive inflammation, easy infection, and impaired angiogenesis in wound beds. The immunoregulation of macrophages polarization toward M2 phenotype that facilitates the transition from inflammation to proliferation phase has been proved to be an effective way to improve diabetic wound healing. Herein, an M2 phenotype-enabled anti-inflammatory, antioxidant, and antibacterial conductive hydrogel scaffolds (GDFE) for producing rapid angiogenesis and diabetic wound repair are reported. The GDFE scaffolds are fabricated facilely through the dynamic crosslinking between polypeptide and polydopamine and graphene oxide. The GDFE scaffolds possess thermosensitivity, self-healing behavior, injectability, broad-spectrum antibacterial activity, antioxidant and anti-inflammatory ability, and electronic conductivity. GDFE effectively activates the polarization of macrophages toward M2 phenotype and significantly promotes the proliferation of dermal fibroblasts, the migration, and in vitro angiogenesis of endothelial cells through paracrine mechanisms. The in vivo results from a full-thickness diabetic wound model demonstrate that GDFE can rapidly promote the diabetic wound repair and skin regeneration, through fast anti-inflammation and angiogenesis and M2 macrophage polarization. This study provides highly efficient strategy for treating diabetic wound repair through designing the M2 polarization-enabled anti-inflammatory, antioxidant, and antibacterial bioactive materials.     

火电机组一次调频性能实时监测系统

为了实时监测和评价火电机组一次调频性能，开发了火电机组一次调频性能实测监测系统。该系统具有一次调频参数异动感知、一次调频性能量化预测及自适应校正等关键功能。某机组的实际应用表明，该系统能够实现火电机组一次调频关键参数的实时监测和调频性能的准确预测。     

Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency

Endoplasmic reticulum (ER) stress response is an adaptive program to cope with cellular stress that disturbs the function and homeostasis of ER, which commonly occurs during cancer progression to late stage. Late-stage cancers, mostly requiring chemotherapy, often develop treatment resistance. Chemoresistance has been linked to ER stress response; however, most of the evidence has come from studies that correlate the expression of stress markers with poor prognosis or demonstrate proapoptosis by the knockdown of stress-responsive genes. Since ER stress in cancers usually persists and is essentially not induced by genetic manipulations, we used low doses of ER stress inducers at levels that allowed cell adaptation to occur in order to investigate the effect of stress response on chemoresistance. We found that prolonged tolerable ER stress promotes mesenchymal–epithelial transition, slows cell-cycle progression, and delays the S-phase exit. Consequently, cisplatin-induced apoptosis was significantly decreased in stress-adapted cells, implying their acquisition of cisplatin resistance. Molecularly, we found that proliferating cell nuclear antigen (PCNA) ubiquitination and the expression of polymerase η, the main polymerase responsible for translesion synthesis across cisplatin-DNA damage, were up-regulated in ER stress-adaptive cells, and their enhanced cisplatin resistance was abrogated by the knockout of polymerase η. We also found that a fraction of p53 in stress-adapted cells was translocated to the nucleus, and that these cells exhibited a significant decline in the level of cisplatin-DNA damage. Consistently, we showed that the nuclear p53 coincided with strong positivity of glucose-related protein 78 (GRP78) on immunostaining of clinical biopsies, and the cisplatin-based chemotherapy was less effective for patients with high levels of ER stress. Taken together, this study uncovers that adaptation to ER stress enhances DNA repair and damage tolerance, with which stressed cells gain resistance to chemotherapeutics.     

Effects of Z-value on physicochemical and biological properties of β-SiAlONs ceramics

This study evaluated the effects of different Z-values on the physical, chemical, and biological properties of β-SiAlON ceramics. Increasing the Z-value of the β-Si₃N₄ solid solution's main phase resulted in the replacement of Si–N bonds with Al–O bonds. The number of columnar crystals decreased, bulk density increased, and porosity decreased, thus transforming the fine-particle microstructure of β-Si₃N₄ into the columnar structure of β-SiAlON. The compressive strength increased, which facilitated sintering at 1500 °C without sintering auxiliaries. H⁺ and OH⁻ ions in deionized water broke the covalent bonds on the β-SiAlON surface, thereby forming new Si–OH, Al–OH, and N–H bonds on the β-SiAlON surface and producing SiO₄⁴⁻, AlO₂⁻, and NH₄⁺ groups in the solution. Increasing the soaking time changed the compositions of ionized H⁺ and OH⁻ ions, thus increasing the pH. MC3T3-E1 cells were cultured on the β-SiAlON surface, and it was observed that the increase in the Z-value of β-SiAlON had no influence on cell adhesion and spreading, but it may slightly suppress cell proliferation at high Z-values. At low Z-values, the low AlO₂⁻ concentration helps promote osteogenic differentiation and mineralized nodule formation. Thus, β-SiAlON ceramics possess excellent physical, chemical, and biological properties and are considered excellent bone-repairing materials.     

Structural insights into peptide self-assembly using photo-induced crosslinking experiments and discontinuous molecular dynamics

Determining the structure of the (oligomeric) intermediates that form during the self-assembly of amyloidogenic peptides is challenging because of their heterogeneous and dynamic nature. Thus, there is need for methodology to analyze the underlying molecular structure of these transient species. In this work, a combination of fluorescence quenching, photo-induced crosslinking (PIC) and molecular dynamics simulation was used to study the assembly of a synthetic amyloid-forming peptide, Aβ_16-22. A PIC amino acid containing a trifluormethyldiazirine (TFMD) group—Fmoc(TFMD)Phe—was incorporated into the sequence (Aβ*_16–22). Electrospray ionization ion-mobility spectrometry mass-spectrometry (ESI-IMS-MS) analysis of the PIC products confirmed that Aβ*_16–22 forms assemblies with the monomers arranged as anti-parallel, in-register β-strands at all time points during the aggregation assay. The assembly process was also monitored separately using fluorescence quenching to profile the fibril assembly reaction. The molecular picture resulting from discontinuous molecule dynamics simulations showed that Aβ_16-22 assembles through a single-step nucleation into a β-sheet fibril in agreement with these experimental observations. This study provides detailed structural insights into the Aβ_16-22 self-assembly processes, paving the way to explore the self-assembly mechanism of larger, more complex peptides, including those whose aggregation is responsible for human disease.     

Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways

The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.     

Practical Application of the Probabilistic‐Statistical Model of the Suspension Separation in Hydrocyclones

An effective practical approach that allows not only a significant reduction in the scope of practical experiments in the course of studying suspension separation processes in hydrocyclones, but also makes it possible to assess the intensity of random components of the processes and define the interrelation between such components and hydrodynamics of flows in a hydrocyclone is presented. Within the frames of the developed probabilistic‐statistical model of suspension separation in hydrocyclones on the basis of statistical self‐similarity properties, a relationship was found between determined and random components of the processes. This allowed transitioning from three‐parameter probability density functions for suspension particles in hydrocyclones to two‐parameter functions; thus significantly improving the efficiency of practical application of the developed model.     

Magnetic Assembly of a Multifunctional Guidance Conduit for Peripheral Nerve Repair

Nerve growth conduits are designed to support and promote axon regeneration following nerve injuries. Multifunctionalized conduits with combined physical and chemical cues, are a promising avenue aimed at overcoming current therapeutic barriers. However, the efficacious assembly of conduits that promote neuronal growth remains a challenge. Here, a biomimetic regenerative gel is developed, that integrates physical and chemical cues in a biocompatible “one pot reaction” strategy. The collagen gel is enriched with magnetic nanoparticles coated with nerve growth factor (NGF). Then, through a remote magnetic actuation, highly aligned fibrillar gel structure embedded with anisotropically distributed coated nanoparticles, combining multiple regenerating strategies, is obtained. The effects of the multifunctional gels are examined in vitro, and in vivo in a 10-mm rat sciatic nerve injury model. The magneto-based therapeutic conduits demonstrate oriented and directed axonal growth, and improve nerve regeneration in vivo. The study of multifunctional guidance scaffolds that can be implemented efficiently and remotely provides the foundation to a novel therapeutic approach to overcome current medical obstacles for nerve injuries.