Bacillus Calmette - Guerin (BCG) is an immune regulator that can enhance hippocampal synaptic plasticity in rats; however, it is unclear whether it can improve synaptic function in a mouse model with ...Alzheimer's disease (AD). We hypothesized that BCG plays a protective role in AD mice and investigated its effect on dendritic morphology. The results obtained show that BCG immunization significantly increases dendritic complexity, as indicated by the increased number of dendritic intersections and branch points, as well as the increase in the fractal dimension. Furthermore, the number of primary neurites and dendritic length also increased following BCG immunization, which increased the number of spines and promoted maturation. IFN-γ and IL-4 levels increased, while TNF-α levels decreased following BCG immunization; expression levels of p-JAK2, P-STAT3, SYN, and PSD-95 also increased. Therefore, this study demonstrates that BCG immunization in APP/PS1 mice mitigated hippocampal dendritic spine pathology, especially after the third round of immunization. This effect could possibly be attributed to; changes in dendritic arborization and spine morphology or increases in SYN and PSD-95 expression levels. It could also be related to mechanisms of BCG-induced increases in IFN-γ or IL-4/JAK2/STAT3 levels.
BCG immunization in a mouse model for Alzheimer's disease significantly increased dendritic complexity, as indicated by an increase in the number of dendritic intersections and branch points, as well as an increase in the fractal dimension of hippocampal CA1 neurons.
The atomic-local environment of catalytically active sites plays an important role in tuning the activity of carbon-based metal-free electrocatalysts (C-MFECs). However, the rational regulation of ...the environment is always impeded by synthetic limitations and insufficient understanding of the formation mechanism of the catalytic sites. Herein, the possible cleavage mechanism of carbon nanotubes (CNTs) through the crossing points during ball-milling is proposed, resulting in abundant CNT tips those are more susceptible to be modified by heteroatoms, achieving precise modulation of the atomic environment at the tips. The obtained CNTs with N, S-rich tips (N,S-TCNTs) exhibit a wide potential window of 0.59 V along with H
O
selectivity for over 90.0%. Even using air as the O
source, the flow cell system with N,S-TCNTs catalyst attains high H
O
productivity up to 30.37 mol g
h
@350 mA cm
, superior to most reported C-MFECs. From a practical point of view, a solid electrolyzer based on N,S-TCNTs is further employed to realize the in-situ continuous generation of pure H
O
solution with high productivity (up to 4.35 mmol cm
h
@300 mA cm
; over 300 h). The CNTs with functionalized tips hold a great permission for practical applications, even beyond H
O
generation. This article is protected by copyright. All rights reserved.
Varieties of contrast agents have been developed for photoacoustic (PA) and ultrasound (US) imaging of cancers
in vivo
. However, access of traditional contrast agents into the sites of tumors has ...been principally through passive infiltration without any external force, preventing their deep penetration into the tissues of the tumors, and hindering the use of PA and US for deep tumor imaging. The concept of micro/nanomotors has been the focus of increasing attention as active theranostic agents due to their active movement in particular fluids, thereby conducting assigned tasks. Herein, US-propelled Janus mesoporous SiO
2
partially coated gold nanorods (Au NR-mSiO
2
) were fabricated for deep tumor NIR-II PA imaging and synergistic sonodynamic-gas therapy. Following US irradiation, 2,2-azobis2-(2-imidazolin-2-yl) propane dihydrochloride (AIPH) loaded in mSiO
2
(Au NR-mSiO
2
/AIPH) generated N
2
microbubbles with high efficiency to achieve nanomotor drive. Due to the deep penetration of US, the nanomotors exhibited a capability to travel deep within sites of tumors, providing enhanced PA/US imaging inside the tumors. Furthermore, the nanomotor based cancer therapy was demonstrated through synergistic N
2
gas and sonodynamic therapy. The US-propelled nanomotors demonstrated a novel strategy for the simultaneous PA/US dual imaging deep within tumor tissues and precise therapy of large tumors.
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•Two novel BTT-based hydrazone-linked COFs are constructed for the first time.•Conjugated BTT broadens the light absorption and enhances the carrier transfer.•Electron-rich BTT builds ...strong built-in electric field within the COFs.•H2 evolution rate reaches 17.27 mmol g-1h−1, a record for hydrazone-linked COFs.•Noble metal-free CO2 photoreduction to CO rate reaches 774.3 μmol g-1h−1.
Hydrazone-linked COFs have shown promising potential in photocatalysis, but still face problems of limited visible-lightabsorption and inefficient photocarrier separation/transportation. Herein, electron-rich and conjugated benzotrithiophene (BTT) is introduced into the aldehyde monomer to get two novel BTT-based hydrazone-linked COFs (BTT-Hz-1, −2). Systematical experiments and theoretical calculations show that comparing with the benzene aldehyde-based COFs (TFB-Hz-1, −2), conjugated structure of BTT broadens the visible-light absorption range and improves the transfer efficiency of the photocarriers; electron-rich structure of BTT constructs strong built-in electric field within the COFs, therefore promotes theseparationofphotocarriers. As a result, BTT-Hz-1 shows a recorded photocatalytic H2 evolution rate for hydrazone-linked COFs of 17.27 mmol g-1h−1, 22 times than that of TFB-Hz-1, and also reveals noble metal-free CO2 photoreduction property with CO evolution rate of 774.3 μmol g-1h−1. This work presents the importance of electronic structure modulation to the COF-based photocatalysis, and opens a new avenue to improve the photocatalysis performance of hydrazone-linked COFs.
Density functional theory (DFT) calculations have been implemented to investigate the helium trapping effect in multi-vacancies, and the stability and energetics of HenVm complexes (n = 0–6, ...m = 0–4). The existence of Cr inhibits the capture of helium atoms in multiple vacancies to some extent. A stronger helium self-trapping aggregation than that in pure iron was found in Fe–Cr alloys. In the early stage of nucleation, the HenVm complexes with higher density in Fe–Cr alloys provide more annihilation sites for the irradiation induced recombination of Frankel pairs, and have higher irradiation swelling resistance than pure iron. A new mechanism has been found that the possibility of the formation of helium-vacancy complexes depends on the helium atoms (n) or vacancies (m). Our simulation results corroborate that when the n/m ratio tends to increase, there is spontaneous emission of helium atoms or self-interstitial atoms (SIAs), and it is difficult to grow helium-vacancy-type complexes in Fe–Cr alloys, which provides necessary information for explaining complex experimental phenomena.
•The existence of Cr inhibits the capture of helium atoms in multiple vacancies.•A stronger helium self-trapping aggregation was found in Fe–Cr alloys.•Fe–Cr alloys have better irradiation swelling resistance.•It is difficult to grow helium-vacancy-type complexes in Fe–Cr alloys.
Gliomas are the most common malignant brain tumors. High-grade gliomas, represented by glioblastoma multiforme (GBM), have a poor prognosis and are prone to recurrence. The standard treatment ...strategy is tumor removal combined with radiotherapy and chemotherapy, such as temozolomide (TMZ). However, even after conventional treatment, they still have a high recurrence rate, resulting in an increasing demand for effective anti-glioma drugs. Drug repurposing is a method of reusing drugs that have already been widely approved for new indication. It has the advantages of reduced research cost, safety, and increased efficiency. Disulfiram (DSF), originally approved for alcohol dependence, has been repurposed for adjuvant chemotherapy in glioma. This article reviews the drug repurposing method and the progress of research on disulfiram reuse for glioma treatment.
PTEN is a dual-specificity phosphatase that is frequently mutated in human cancer, and its deficiency in cancer has been associated with therapy resistance and poor survival. Although the intrinsic ...tumour-suppressor function of PTEN has been well established, evidence of its role in the tumour immune microenvironment is lacking. Here, we show that chemotherapy-induced antitumour immune responses and tumour suppression rely on myeloid-cell PTEN, which is essential for chemotherapy-induced activation of the NLRP3 inflammasome and antitumour immunity. PTEN directly interacts with and dephosphorylates NLRP3 to enable NLRP3-ASC interaction, inflammasome assembly and activation. Importantly, supplementation of IL-1β restores chemotherapy sensitivity in mouse myeloid cells with a PTEN deficiency. Clinically, chemotherapy-induced IL-1β production and antitumour immunity in patients with cancer is correlated with PTEN expression in myeloid cells, but not tumour cells. Our results demonstrate that myeloid PTEN can determine chemotherapy responsiveness by promoting NLRP3-dependent antitumour immunity and suggest that myeloid PTEN might be a potential biomarker to predict chemotherapy responses.
Airy beams exhibit intriguing properties such as nonspreading, self-bending, and self-healing and have attracted considerable recent interest because of their many potential applications in ...photonics, such as to beam focusing, light-sheet microscopy, and biomedical imaging. However, previous approaches to generate Airy beams using photonic structures have suffered from severe chromatic problems arising from strong frequency dispersion of the scatterers. Here, we design and fabricate a metasurface composed of silicon posts for the frequency range 0.4–0.8 THz in transmission mode, and we experimentally demonstrate achromatic Airy beams exhibiting autofocusing properties. We further show numerically that a generated achromatic Airy-beam-based metalens exhibits self-healing properties that are immune to scattering by particles and that it also possesses a larger depth of focus than a traditional metalens. Our results pave the way to the realization of flat photonic devices for applications to noninvasive biomedical imaging and light-sheet microscopy, and we provide a numerical demonstration of a device protocol.
Bisphenol-A (BPA) is known to be a potent endocrine disrupter. Evidence is emerging that estrogen exerts a rapid influence on hippocampal synaptic plasticity and the dendritic spine density, which ...requires activation of NMDA receptors. In the present study, we investigated the effects of BPA (ranging from 1 to 1000
nM), focusing on the rapid dynamic changes in dendritic filopodia and the expressions of estrogen receptor (ER) β and NMDA receptor, as well as the phosphorylation of NMDA receptor subunit NR2B in the cultured hippocampal neurons. A specific ER antagonist ICI 182,780 was used to examine the potential involvement of ERs. The results demonstrated that exposure to BPA (ranging from 10 to 1000
nM) for 30
min rapidly enhanced the motility and the density of dendritic filopodia in the cultured hippocampal neurons, as well as the phosphorylation of NR2B (pNR2B), though the expressions of NMDA receptor subunits NR1, NR2B, and ERβ were not changed. The antagonist of ERs completely inhibited the BPA-induced increases in the filopodial motility and the number of filopodia extending from dendrites. The increased pNR2B induced by BPA (100
nM) was also completely eliminated. Furthermore, BPA attenuated the effects of 17β-estradiol (17β-E
2) on the dendritic filopodia outgrowth and the expression of pNR2B when BPA was co-treated with 17β-E
2. The present results suggest that BPA, like 17β-E
2, rapidly results in the enhanced motility and density of dendritic filopodia in the cultured hippocampal neurons with the concomitant activation of NMDA receptor subunit NR2B via an ER-mediated signaling pathway. Meanwhile, BPA suppressed the enhancement effects of 17β-E
2 when it coexists with 17β-E
2. These results provided important evidence suggesting the neurotoxicity of the low levels of BPA during the early postnatal development of the brain.
During the Mid-Miocene Climatic Optimum MMCO, ~14 to 17 million years (Ma) ago, global temperatures were similar to predicted temperatures for the coming century. Limited megathermal paleoclimatic ...and fossil data are known from this period, despite its potential as an analog for future climate conditions. Here, we report a rich middle Miocene rainforest biome, the Zhangpu biota (~14.7 Ma ago), based on material preserved in amber and associated sedimentary rocks from southeastern China. The record shows that the mid-Miocene rainforest reached at least 24.2°N and was more widespread than previously estimated. Our results not only highlight the role of tropical rainforests acting as evolutionary museums for biodiversity at the generic level but also suggest that the MMCO probably strongly shaped the East Asian biota via the northern expansion of the megathermal rainforest biome. The Zhangpu biota provides an ideal snapshot for biodiversity redistribution during global warming.
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