The Deacetylase HDAC6 Mediates Endogenous Neuritic Tau Pathology

The initiating events that promote tau mislocalization and pathology in Alzheimer's disease (AD) are not well defined, partly because of the lack of endogenous models that recapitulate tau dysfunction. We exposed wild-type neurons to a neuroinflammatory trigger and examined the effect on endogenous tau. We found that tau re-localized and accumulated within pathological neuritic foci, or beads, comprised of mostly hypo-phosphorylated, acetylated, and oligomeric tau. These structures were detected in aged wild-type mice and were enhanced in response to neuroinflammation in vivo, highlighting a previously undescribed endogenous age-related tau pathology. Strikingly, deletion or inhibition of the cytoplasmic shuttling factor HDAC6 suppressed neuritic tau bead formation in neurons and mice. Using mass spectrometry-based profiling, we identified a single neuroinflammatory factor, the metalloproteinase MMP-9, as a mediator of neuritic tau beading. Thus, our study uncovers a link between neuroinflammation and neuritic tau beading as a potential early-stage pathogenic mechanism in AD

Color center formation in alpha-Al2O3 induced by high energy heavy ions

Single crystals of alpha-alumina were irradiated at room temperature with 1.157 (GeVFe)-Fe-56, 1.755 (GeVXe)-Xe-136 and 2.636 (GeVU)-U-238 ions to fluences range from 8.7 x 10(9) to 6 x 10(12) ions/cm(2). Virgin and irradiated samples were investigated by ultraviolet visible absorption measurements. The investigation reveals the presence of various color centers (F, F+, F-2(2+), F-2(+) and F-2 centers) appearing in the irradiated samples. It is found that the ratio of peak absorbance of F-2 to F centers increases with the increase of the atomic numbers of the incident ions from Fe, Xe to U ions, so do the absorbance ratio of F-2(2+) to F+ centers and of large defect cluster to F centers, indicating that larger defect clusters are preferred to be produced under heavier ion irradiation. Largest color center production cross-section was found for the U ion irradiation. The number density of single anion vacancy scales better with the energy deposition through processes of nuclear stopping, indicating that the nuclear energy loss processes determines the production of F-type defects in heavy ion irradiated alpha-alumina

Side-Chain Engineering of Aggregation-Induced Emission Molecules for Boosting Cancer Phototheranostics

The ingenious construction of versatile cancer phototheranostic agents involving FLI, PDT, and PTT concurrently has attracted great interest. By virtue of the plentiful freely rotated moieties and the inherent twisted structure, AIEgens have been proven a perfect template for development of phototheranostic system. The systematic regulation of the energy consumption pathways through altering the molecular structure of AIEgens based on side-chain engineering is of great significance for the simultaneous pursuit of controllable fluorescence, photodynamic and photothermal properties, but has rarely been reported. Herein, an AIE-active multifunctional phototheranostic system was reported through intentional control the side-chain structure. Bearing the longest alkyl chain, all of those three energy dissipation pathways were retained controllably. In vitro and in vivo evaluations verified that TBFT2 nanoparticles performed well in terms of FLI-guided PDT and PTT synergistic cancer therapy. This study provides a new insight into the exploration of superior versatile phototheranostics through side-chain engineering

A study of the suppression of the high-temperature helium embrittlement in an oxide-particle dispersion strengthened alloy

In this paper, an investigation on the micro-structure of an Fe-base oxide-dispersion-strengthened (ODS) alloy irradiated with high-energy Ne-20 ions to different doses at a temperature around 0.5T(m) (T-m is the melting point of the alloy) is presented. Investigation with the transmission electron microscopy found that the accelerated growth of voids at grain-boundaries, which is usually a concern in conventional Fe-base alloys under conditions of inert-gas implantation, was not observed in the ODS alloy irradiated even to the highest dose (12000 at.ppm Ne). The reason is ascribed to the enhanced recombination of point defects and strong trapping of Ne atoms at the interfaces of the nano-scale oxide particles in grains. The study showed that ODS alloys have good resistance to the high-temperature inter-granular embrittlement due to inert-gas accumulation, exhibiting prominence of application in harsh situations of considerable helium production at elevated temperatures like in a fusion reactor.NSAF Joint Foundation of China 1037603

A study of the suppression of the high-temperature helium embrittlement in an oxide-particle dispersion strengthened alloy

In this paper, an investigation on the micro-structure of an Fe-base oxide-dispersion-strengthened (ODS) alloy irradiated with high-energy Ne-20 ions to different doses at a temperature around 0.5T(m) (T-m is the melting point of the alloy) is presented. Investigation with the transmission electron microscopy found that the accelerated growth of voids at grain-boundaries, which is usually a concern in conventional Fe-base alloys under conditions of inert-gas implantation, was not observed in the ODS alloy irradiated even to the highest dose (12000 at.ppm Ne). The reason is ascribed to the enhanced recombination of point defects and strong trapping of Ne atoms at the interfaces of the nano-scale oxide particles in grains. The study showed that ODS alloys have good resistance to the high-temperature inter-granular embrittlement due to inert-gas accumulation, exhibiting prominence of application in harsh situations of considerable helium production at elevated temperatures like in a fusion reactor.NSAF Joint Foundation of China 1037603

Pillar[5]arene-Modified Gold Nanorods as Nanocarriers for Multi-Modal Imaging-Guided Synergistic Photodynamic-Photothermal Therapy

Supramolecular approaches have opened up vast possibilities in the construction of versatile functional materials, especially those with stimuli-responsiveness and integrated functionalities of multi-modal diagnosis and synergistic therapeutics. In this study, a hybrid theranostic nanosystem named TTPY-PyÌCP5@AuNR is constructed via facile host-guest interactions, where TTPY-Py is a photosensitizer with aggregation-induced emission and CP5@AuNR represents the carboxylatopillar[5]arene (CP5)-modified Au nanorods. TTPY-PyÌCP5@AuNR integrates the respective advantages of TTPY-Py and CP5@AuNR such as the high performance of reactive oxygen species (ROS) generation and photothermal conversion, and meanwhile shows fluorescence responses to both temperature and pH stimuli due to the non-covalent interactions. The successful modification of CP5 macrocycles on AuNRs surfaces can eliminate the cytotoxicity of AuNRs and enable them to serve as the nanocarrier of TTPY-Py for further theranostic application. Significantly, both in vitro and in vivo evaluations demonstrate that this supramolecular nanotheranostic system possesses multiple phototheranostic modalities including intensive fluorescence imaging (FLI), photoacoustic imaging (PAI), efficient photodynamic therapy (PDT), and photothermal therapy (PTT), indicating its great potentials for FLI-PAI imaging-guided synergistic PDT-PTT therapy. Besides, TTPY-Py can be released from the nanocarriers upon activating by the acidic environment of lysosomes and then specifically light up mitochondria. This study brings up a new strategy into the design of versatile nanotheranostics for accurate tumor imaging and cancer therapies