Astrocytes modulate brain phosphate homeostasis via polarized distribution of phosphate uptake transporter PiT2 and exporter XPR1.

Aberrant inorganic phosphate (Pi) homeostasis causes brain calcification and aggravates neurodegeneration, but the underlying mechanism remains unclear. Here, we found that primary familial brain calcification (PFBC)-associated Pi transporter genes Pit2 and Xpr1 were highly expressed in astrocytes, with importer PiT2 distributed over the entire astrocyte processes and exporter XPR1 localized to astrocyte end-feet on blood vessels. This polarized PiT2 and XPR1 distribution endowed astrocyte with Pi transport capacity competent for brain Pi homeostasis, which was disrupted in mice with astrocyte-specific knockout (KO) of either Pit2 or Xpr1. Moreover, we found that Pi uptake by PiT2, and its facilitation by PFBC-associated galactosidase MYORG, were required for the high Pi transport capacity of astrocytes. Finally, brain calcification was suppressed by astrocyte-specific PiT2 re-expression in Pit2-KO mice. Thus, astrocyte-mediated Pi transport is pivotal for brain Pi homeostasis, and elevating astrocytic Pi transporter function represents a potential therapeutic strategy for reducing brain calcification.

Association of homocysteine with ankylosing spondylitis: a systematic review and meta-analysis.

BACKGROUND: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. METHODS: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. RESULTS: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = - 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. CONCLUSION: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. TRIAL REGISTRATION: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426 .

Association of homocysteine with ankylosing spondylitis: a systematic review and meta-analysis

Abstract Background: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.(AU)

Uniform yolk-shell structured Si-C nanoparticles as a high performance anode material for the Li-ion battery.

Silicon (Si) is a promising candidate as an anode material for lithium-ion batteries. However, its application is hindered by poor cycling stability and rate-capability due to structural degradation, resulting from large volume changes during cyclic charging and discharging. In this paper, we report that uniform-sized Si@void@C nanoparticles can be prepared by magnesiothermic reduction of SiO2@void@C. Si nanoparticles are in hollow carbon shells with a large void space between the carbon shell and particles. Thus, each Si particle can expand freely within the well-designed void space without destroying the outer carbon shell, and benefit the solid-electrolyte interphase film stabilization on the carbon shell. The new material shows a high capacity of 1598 mA h g-1 at a current density of 1 A g-1, a long cycle life of 1500 cycles with 85% capacity retention, and a high Coulombic efficiency of 99.6% as well, and might be a promising Si-based anode material for Li-ion battery applications.

A Bioinspired Functionalization of Polypropylene Separator for Lithium-Sulfur Battery.

Lithium-sulfur batteries have received intensive attention, due to their high specific capacity, but the shuttle effect of soluble polysulfide results in a decrease in capacity. In response to this issue, we develop a novel tannic acid and Au nanoparticle functionalized separator. The tannic acid and gold nanoparticles were modified onto commercial polypropylene separator through a two-step solution process. Due to a large number of phenolic hydroxyl groups contained in the modified layer and the strong polarity of the gold nanoparticles, the soluble polysulfide generated during battery cycling is well stabilized on the cathode side, slowing down the capacity fade brought by the shuttle effect. In addition, the modification effectively improves the electrolyte affinity of the separator. As a result of these benefits, the novel separator exhibits improved battery performance compared to the pristine polypropylene separator.

Nanoporous-Gold-Based Hybrid Cantilevered Actuator Dealloyed and Driven by A Modified Rotary Triboelectric Nanogenerator.

We firstly designed an electrochemical system for dealloying to synthesize nanoporous gold (NPG) and also driving the novel NPG based actuator by utilizing a modified rotary triboelectric nanogenerator (TENG). Compared to the previous reported TENG whose outputs decline due to temperature rising resulting from electrodes friction, the modified TENG with a cooling system has stable output current and voltage increased by 14% and 20%, respectively. The novel cantilevered hybrid actuator characterised by light-weight (ca. 3 mg) and small volume (ca. 30 mm × 2 mm × 10 µm) is driven by a microcontroller modulated TENG with the displacement of 2.2 mm, which is about 10(6) times larger than that of traditional cantilever using planar surfaces. The energy conversion efficiencies defined as the energy consumed during dealloying and actuation compared with the output of TENG are 47% and 56.7%, respectively.

Facile synthesis and characterization of water soluble ZnSe/ZnS quantum dots for cellar imaging.

Strong fluorescence and low cytotoxicity ZnSe/ZnS quantum dots (QDs) were synthesized by a facile aqueous phase route. It overcame the defects such as instability and low quantum yield of the quantum dots synthesized by early aqueous phase route. L-Glutathione (GSH) and 3-mercaptopropaonic acid (MPA) were used as mixture stabilizers to synthesize high quality ZnSe/ZnS QDs. The samples were characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectrometry (XPS) and their optical properties were investigated by using UV-vis spectrophotometer, fluorescence spectrophotometer (FL), IR spectrophotometer and confocal laser scanning microscope. The synthesized ZnSe/ZnS QDs illuminated blue fluorescence under ultraviolet lamp. Its water-soluble property is excellent and the fluorescence intensity of ZnSe/ZnS QDs almost did not change after 4 months at room temperature. The average diameter of ZnSe/ZnS nanocrystals is about 3 nm and quantum yield (QY) could reach to 70.6% after repeat determination. Low cytotoxicity was ensured by investigated SCG7901 and RAW264.7 cells. In comparison with cadmium based nanocrystals, ZnSe/ZnS QDs posed low cytotoxicity. The cells viability remained 96.7% when the QDs concentration was increased to 10 µmol/L. The results in vitro indicate that ZnSe/ZnS QDs-based probes have good stability, low toxicity and biocompatibility for fluorescence imaging in cancer model system.

Engineered redox-responsive PEG detachment mechanism in PEGylated nano-graphene oxide for intracellular drug delivery.

In biomedical applications, polyethylene glycol (PEG) functionalization has been a major approach to modify nanocarriers such as nano-graphene oxide for particular biological requirements. However, incorporation of a PEG shell poses a significant diffusion barrier that adversely affects the release of the loaded drugs. This study addresses this critical issue by employing a redox-responsive PEG detachment mechanism. A PEGylated nano-graphene oxide (NGO-SS-mPEG) with redox-responsive detachable PEG shell is developed that can rapidly release an encapsulated payload at tumor-relevant glutathione (GSH) levels. The PEG shell grafted onto NGO sheets gives the nanocomposite high physiological solubility and stability in circulation. It can selectively detach from NGO upon intracellular GSH stimulation. The surface-engineered structures are shown to accelerate the release of doxorubicin hydrochloride (DXR) from NGO-SS-mPEG 1.55 times faster than in the absence of GSH. Confocal microscopy shows clear evidence of NGO-SS-mPEG endocytosis in HeLa cells, mainly accumulated in cytoplasm. Furthermore, upon internalization of DXR-loaded NGO with a disulfide-linked PEG shell into HeLa cells, DXR is effectively released in the presence of an elevated GSH reducing environment, as observed in confocal microscopy and flow cytometric experiments. Importantly, inhibition of cell proliferation is directly correlated with increased intracellular GSH concentrations due to rapid DXR release.

Self-assembling nanomicelles of a novel camptothecin prodrug engineered with a redox-responsive release mechanism.

A novel amphiphilic camptothecin prodrug that spontaneously arranges into nanomicelles which preferentially release the cytotoxic drug under tumor-relevant reductive conditions is designed.