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α-Synuclein (α-syn) can form oligomers, protofibrils, and fibrils, which are associated with the pathogenesis of Parkinson's disease and other synucleinopathies. Both the lipid peroxidation product 4-oxo-2-nonenal (ONE) and agitation can induce aggregation of α-syn and phosphorylated α-syn. Thus, clarification of the characteristics of different α-syn species could help to select suitable aggregates for diagnosis and elucidate the pathogenesis of diseases. Here, we characterized ONE-induced wild-type (WT) α-syn aggregates (OW), ONE-induced phosphorylated α-syn (p-α-syn) aggregates (OP), agitation-induced α-syn preformed fibrils (PFF), and agitation-induced p-α-syn preformed fibrils (pPFF). Thioflavin T (ThT) dying demonstrated that OW and OP had fewer fibrils than the PFF and pPFF. Transmission electron microscopy revealed that the lengths of PFF and pPFF were similar, but the diameters differed. OW and OP had more compact structures than PFF and pPFF. Aggregation of p-α-syn was significantly faster than WT α-syn. Furthermore, OW and OP were more sodium dodecyl sulfate-stable and proteinase K-resistant, suggesting greater stability and compactness, while aggregates of PFF and pPFF were more sensitive to proteinase K treatment. Both ONE- and agitation-induced aggregates were cytotoxic when added exogenously to SH-SY5Y cells with increasing incubation times, but the agitation-induced aggregates caused cell toxicity in a shorter time and more p-α-syn inclusions. Similarly, p-proteins were more cytotoxic than non-p-proteins. Finally, all four aggregates were used as standard antigens to establish sandwich enzyme-linked immunosorbent assay (ELISA). The results showed that the recognition efficiency of OW and OP was more sensitive than that of PFF and pPFF. The OW- and OP-specific ELISA for detection of p-α-syn and α-syn in plasma samples of Thy1-α-syn transgenic mice showed that the content of aggregates could reflect the extent of disease. ONE and agitation induced the formation of α-syn aggregates with distinct biophysical properties and biomedical applications. [ABSTRACT FROM AUTHOR]

Aims: The etiology of Parkinson's disease (PD) is complex and the mechanism is unclear. It has become a top priority to find common factors that induce and affect PD pathology. We explored the key role of hypoxia in promoting the pathological propagation of α‐synuclein (α‐syn) and the progression of PD. Methods: We performed PD modeling by conducting intracranial stereotaxic surgery in the unilateral striatum of mice. We then measured protein aggregation in vitro. The rotarod and pole tests were employed next to measure the damage of the phenotype. Pathological deposition and autophagy were also observed by immunofluorescence staining and protein levels measured by western blotting. Results: We demonstrated that short‐term hypoxia activated phosphorylated (p)‐α‐syn in mice. We confirmed that p‐α‐syn was more readily formed aggregates than α‐syn in vitro. Furthermore, we found that hypoxia promoted the activation and propagation of endogenous α‐syn, contributing to the earlier degeneration of dopaminergic neurons in the substantia nigra and the deposition of p‐α‐syn in our animal model. Finally, autophagy inhibition contributed to the above pathologies. Conclusion: Hypoxia was shown to accelerate the pathological progression and damage phenotype in PD model mice. The results provided a promising research target for determining common interventions for PD in the future. [ABSTRACT FROM AUTHOR]

Shelterin, a protective complex at telomeres, plays essential roles in cancer. In addition to maintain telomere integrity, shelterin functions in various survival pathways. However, the detailed mechanisms of shelterin regulation in cancer remain elusive. Here, we perform a comprehensive analysis of shelterin in 9125 tumor samples across 33 cancer types using multi-omic data from The Cancer Genome Atlas, and validate some findings in Chinese Glioma Genome Atlas and cancer cell lines from Cancer Cell Line Encyclopedia. In the genomic landscape, we identify the amplification of TRF1 and POT1, co-amplification/deletion of TRF2–RAP1–TPP1 as the dominant alteration events. Clustering analysis based on shelterin expression reveals three cancer clusters with different degree of genome instability. To measure overall shelterin activity in cancer, we derive a shelterin score based on shelterin expression. Pathway analysis shows shelterin is positively correlated with E2F targets, while is negatively correlated with p53 pathway. Importantly, shelterin links to tumor immunity and predicts response to PD-1 blockade immune therapy. In-depth miRNA analysis reveals a miRNA–shelterin interaction network, with p53 regulated miRNAs targeting multiple shelterin components. We also identify a significant amount of lncRNAs regulating shelterin expression. In addition, we find shelterin expression could be used to predict patient survival in 24 cancer types. Finally, by mining the connective map database, we discover a number of potential drugs that might target shelterin. In summary, this study provides broad molecular signatures for further functional and therapeutic studies of shelterin, and also represents a systemic approach to characterize key protein complex in cancer. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disease. The pathogenesis of PD is complicated and remains obscure, but growing evidence suggests the involvement of mitochondrial and lysosomal dysfunction. Mitophagy, the process of removing damaged mitochondria, is compromised in PD patients and models, and was found to be associated with accelerated neurodegeneration. Several PD-related proteins are known to participate in the regulation of mitophagy, including PINK1 and Parkin. In addition, mutations in several PD-related genes are known to cause mitochondrial defects and neurotoxicity by disturbing mitophagy, indicating that mitophagy is a critical component of PD pathogenesis. Therefore, it is crucial to understand how these genes are involved in mitochondrial quality control or mitophagy regulation in the study of PD pathogenesis and the development of novel treatment strategies. In this review, we will discuss the critical roles of mitophagy in PD pathogenesis, highlighting the potential therapeutic implications of mitophagy regulation. [ABSTRACT FROM AUTHOR]

A hybrid UV absorber (SiO2-H) was successfully synthesized by functionalizing nanosilica (SiO2) with 2,4-dihydroxybenzophenone and then was introduced onto the surface of cotton fabric by sequentially depositing in poly (diallyl dimethyl ammonium chloride) (PDDA) aqueous solution and SiO2-H suspension via layer-by-layer assembly method. The SiO2-H particles imparted excellent ultraviolet (UV) resistance property to the cotton fabric, while forming nano- and micro structure on the surface of cotton fabric, making the fabric superhydrophobic after the modification with hexadecyltrimethoxy silane (HDTMS). The surface morphology, wetting behavior, UV resistance and physical properties of cotton fabrics were studied. According to the results, the modified cotton fabric not only showed strong UV-resistant ability with Ultraviolet Protection Factor (UPF) value as high as 500, but also displayed superhydrophobicty with WCA of 153 ± 1°. Moreover, the durability of multifunctional surface was examined by laundering and abrasion tests. The modified fabrics still maintained hydrophobic property and excellent UV resistance after 300 abrasion or 20 laundering cycles, demonstrating outstanding durability. [ABSTRACT FROM AUTHOR]

PET non-woven fabrics and poly (ethylene glycol) dimethacrylate were added to strengthen tensile strength and chemical stability of PAN-MA separators. Besides, PET non-woven fabrics also act as the skeleton to sustain separators at high temperatures, and they can work at even 150 °C. Porous structures of PAN-MA separators are formed by phase inversion, and strengthened by PEGDMA which cross-link at high temperature without adding initiator. Effects of PEGDMA on tensile strength, porosity and ionic conductivity were studied and performances of separators modified by two kinds of molecular weight of PEGDMA were compared. As a result, a battery separator with ionic conductivity of 2.14 mS/cm, tensile strength of 26.7 MPa, porosity of 36.6% was obtained. [ABSTRACT FROM AUTHOR]

Polyethylene/paraffin oil blend sheets with different molecular weights of polyethylene were prepared by thermally induced phase separation. Isothermal and non-isothermal crystallization behaviors of blend sheets were investigated by differential scanning calorimetry (DSC). Isothermal DSC curves were analyzed by Avrami equation, whereas non-isothermal DSC curves were analyzed by Jeziorny method and Mo method. Effective activation energy (Δ E) of isothermal and non-isothermal crystallization was calculated by Friedman method. Under isothermal condition, value of n in Avrami equation hovered at 2.1, and lg Z increased with the decrease of crystallization temperature. lg Z and Δ E of blend sheets with a larger molecular weight of polyethylene was smaller than that of blend sheets with smaller molecular weight. Under non-isothermal condition, value of n obtained by Jeziorny method hovered at 2.4, close to n of isothermal condition. lg Z increased with the increase of cooling rate and decrease of molecular weight of polyethylene. Δ E of different blend sheets were close to each other. Crystal structures of blend sheets formed under non-isothermal condition were analyzed by X-ray diffraction (XRD) analysis. XRD analysis showed that molecular weight of polyethylene and cooling rate had slight influence on crystal structure and crystallinity of polyethylene/paraffin oil blend sheet. [ABSTRACT FROM AUTHOR]