In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aβ) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and ...neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aβ and mediates Aβ-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aβ. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aβ deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aβ deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing β-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aβ toxicity and would be a novel therapeutic target and biomarker for AD.
Background
IL‐25 has been proposed to play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to evaluate the association of IL‐25 with the ...Th2‐biased inflammatory profiles in CRSwNP.
Methods
Nasal polyp (NP) tissues and control uncinate process tissues were collected from 92 patients with CRSwNP, 20 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 16 normal control subjects. IL‐25 expression was examined using immunohistochemistry and immunofluorescence staining, flow cytometry, RT‐qPCR, and ELISA. The inflammatory profiles and clinical characteristics of 2 NP subtypes (IL‐25high and IL‐25low) were evaluated, and the effects of IL‐25 on Th2 cytokine production in cultured dispersed polyp cells were examined in vitro.
Results
The mRNA and protein levels of IL‐25 were significantly increased in the polyp tissues compared with the control uncinate process tissues. The IL‐25high subtype showed greater computed tomography scores, endoscopic scores, and Th2 response. Exposure to IL‐25 activated type 2 innate lymphoid cells and Th2 cells in NP simultaneously which further increased Th2 cytokine production in vitro.
Conclusions
Local IL‐25 plays a crucial role in promoting Th2‐biased inflammatory profiles in NP and may serve as a promising therapeutic target in CRSwNP patients.
Summary
We investigated the secular trends of the incidence and hospitalization cost of hip fracture in Tangshan, China. The incidence of hip fracture and the hospitalization cost were both ...increasing during the observation period.
Introduction
The present study aimed to determine sex-, age-, and fracture type-specific incidence and annual changes in hip fractures in Tangshan, China, between 2007 and 2018.
Methods
We analyzed annual hip fracture incidence using urban hospital data during 2007–2018 and calculated incidence rate/100,000 person years in each age group and sex. We assessed annual changes in incidence among people aged >60 years using linear-by-linear association tests and evaluated hospitalization costs with the Kruskal–Wallis test.
Results
During the study period, we observed an increasing proportion of hip fractures in people >60 years old from 14.2 to 22.79%. Crude hip fracture incidence increased markedly from 140.87 to 306.56/100,000 in women (
p
< 0.01) and from 124.83 to 167.19/100,000 in men (
p
< 0.01) in the age group >60 years. Type-specific analysis indicated significantly increased trends in incidence of cervical and trochanteric fractures among women and cervical fracture among men (
p
< 0.01). In people aged 36–60 years, the trend of hip fracture increased significantly in both sexes. The total and cervical-to-trochanteric ratio in men increased, with significant upward trends (
p
< 0.01). The proportion of cervical fracture was higher than that for trochanteric fracture in women, with stable levels from 2007 to 2018. Hospitalization costs for cervical and trochanteric fractures increased by 51.91% and 53.20%, respectively, during 2011–2018.
Conclusion
Tangshan will have an increasing burden on health care resources attributable to a considerable rise in hip fracture incidence and the older population. Further investigation of risk factors and subsequent implementation of effective measures to prevent hip fracture are needed.
The cross sections of the e+e–→$\phiη'$ process at center-of-mass energies from 3.508 to 4.951 GeV are measured with high precision using 26.1 fb–1 data collected with the BESIII detector operating ...at the BEPCII storage ring. The cross sections are of the order of a few picobarn and decrease as the center-of-mass energy increases as s–n/2 with n = 4.35 ± 0.14. This result is in agreement with the Nambu-Jona-Lasinio model prediction of n = 3.5 ± 0.9. In addition, the charmless decay $\psi$(3770)→$\phiη'$ is searched for by fitting the measured cross sections, yet no significant signal is observed. The upper limit of $\mathscr{B}$($\psi$(3770)→$\phiη'$) at the 90% confidence level is determined to be 2.3 × 10–5.
The deployment of effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to eradicate the coronavirus disease 2019 (COVID-19) pandemic. Many licensed ...vaccines confer protection by inducing long-lived plasma cells (LLPCs) and memory B cells (MBCs), cell types canonically generated during germinal center (GC) reactions. Here, we directly compared two vaccine platforms—mRNA vaccines and a recombinant protein formulated with an MF59-like adjuvant—looking for their abilities to quantitatively and qualitatively shape SARS-CoV-2-specific primary GC responses over time. We demonstrated that a single immunization with SARS-CoV-2 mRNA, but not with the recombinant protein vaccine, elicited potent SARS-CoV-2-specific GC B and T follicular helper (Tfh) cell responses as well as LLPCs and MBCs. Importantly, GC responses strongly correlated with neutralizing antibody production. mRNA vaccines more efficiently induced key regulators of the Tfh cell program and influenced the functional properties of Tfh cells. Overall, this study identifies SARS-CoV-2 mRNA vaccines as strong candidates for promoting robust GC-derived immune responses.
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•SARS-CoV-2 mRNA vaccines elicit potent GC B cell responses•GC responses are associated with a robust development of neutralizing antibodies•SARS-CoV-2 mRNA vaccines promote antigen-specific Tfh cells•Key elements of the Tfh cell program are modulated by SARS-CoV-2 mRNA vaccines
Herein, Lederer et al. show a nucleic-acid-based vaccine platform for SARS-CoV-2 that potently induces germinal center (GC) responses. GCs are microanatomical sites harboring the formation of high-quality, protective antibody responses. Such vaccine platforms can be promising candidates to mitigate the COVID-19 pandemic.
The super τ-charm facility (STCF) is an electron−positron collider proposed by the Chinese particle physics community. It is designed to operate in a center-of-mass energy range from 2 to 7 GeV with ...a peak luminosity of 0.5 × 10 35 cm −2·s −1 or higher. The STCF will produce a data sample about a factor of 100 larger than that of the present τ-charm factory - the BEPCII, providing a unique platform for exploring the asymmetry of matter-antimatter (charge-parity violation), in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions, as well as searching for exotic hadrons and physics beyond the Standard Model. The STCF project in China is under development with an extensive R&D program. This document presents the physics opportunities at the STCF, describes conceptual designs of the STCF detector system, and discusses future plans for detector R&D and physics case studies.
Aims: To identify and compare microbiota in Chinese liquor Daqu, which were produced in the different regions using different production process.
Methods and Results: The DNA exacted from Daqu ...samples was used as a template for PCR with universal primers of 16S rRNA, 26S rRNA and 18S rRNA, respectively. The amplicons were analysed using denaturing gradient gel electrophoresis (DGGE). It was observed that the bacterial DGGE profile indicated high diversity and predominance of lactic acid bacteria. The results showed that Saccharomycopsis fibuligera and Pichia anomal were dominant yeast species and that several non‐Saccharomyces yeasts including Hanseniaspora guilliermondii, Debaryomyces hansenii, Issatchenkia orientalis and Trichosporon asahii were also detected. As for fungal DGGE, Aspergillus oryzae and Absidia blakesleeana were the most common species amongst different samples. Based on the DGGE analysis, a few differences in community structure were found between Daqu samples.
Conclusions: A variety of bacteria, yeast and moulds were identified in Daqu samples, in addition to the present knowledge obtained mainly through the traditional culture‐dependent methods. Moreover, production temperature played a more decisive role on the formation of micro‐organism composition in Daqu than geographical region.
Significance and Impact of the Study: PCR–DGGE technique was used in this study to fully observe and asses all microbial community (including bacteria, yeast and mould) in Chinese liquor Daqu for the first time and proved to be effective in profiling Daqu microbial diversity.
We have clearly discriminated the single-, bilayer-, and multiple-layer graphene (<10 layers) on Si substrate with a 285 nm SiO2 capping layer by using contrast spectra, which were generated from the ...reflection light of a white light source. Calculations based on Fresnel's law are in excellent agreement with the experimental results (deviation 2%). The contrast image shows the reliability and efficiency of this new technique. The contrast spectrum is a fast, nondestructive, easy to be carried out, and unambiguous way to identify the numbers of layers of graphene sheet. We provide two easy-to-use methods to determine the number of graphene layers based on contrast spectra: a graphic method and an analytical method. We also show that the refractive index of graphene is different from that of graphite. The results are compared with those obtained using Raman spectroscopy.
Abstract
Ion Cyclotron Range of Frequencies (ICRF) heating and Neutral Beam Injection (NBI) can have synergy due to the acceleration of NBI beam ions by ICRF wave fields at their harmonics. To ...understand the influence of ICRF-NBI synergy on fast ion distribution and plasma performance, dedicated experiments and TRANSP simulations have been carried out on EAST. The simulation results are consistent with the experimental results. They show that the ICRF-NBI synergy not only accelerates the NBI beam ions with energy lower than 80 keV to energy larger than 300 keV, but also generates fusion neutrons with energy larger than 3 MeV. Moreover, ICRF-NBI synergy improves the plasma performance by increasing the poloidal beta, plasma stored energy, core ion temperature, total neutron yield and kinetic pressure. In a typical H-mode plasma with 1.0 MW NBI and 1.5 MW ICRF power, it was observed that ICRF-NBI synergy increases the poloidal beta, plasma stored energy, core ion temperature and neutron yield by ∼35%, 33%, 22% and 80%, respectively. Various parameter scans show that the ICRF-NBI synergetic effects can be enhanced by decreasing the minority ion concentration or the distance between the harmonic resonance and magnetic axis, or by increasing the ICRF heating power or NBI beam energy. Consequently, this leads to a generation of fast ions with higher energy. For instance, the maximum energy of the fast ion tail increases from 300 to 600 keV as n(H) decreases from 5% to 0.1%.
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