Summary Intervertebral disc (IVD) degeneration is a complicated process that involves both age-related change and tissue damage caused by multiple stresses. In a degenerative IVD, cellular senescence ...accumulates and is associated with reduced proliferation, compromised self-repair, increased inflammatory response, and enhanced catabolic metabolism. In this review, we decipher the senescence mechanism of IVD degeneration (IVDD) by interpreting how aging coordinates with age-related, microenvironment-derived stresses in promoting disc cell senescence and accelerating IVDD. After chronic and prolonged replication, cell senescence may occur as a natural part of the disc aging process, but can potentially be accelerated by growth factor deficiency, oxidative accumulation, and inflammatory irritation. While acute disc injury, excessive mechanical overloading, diabetes, and chronic tobacco smoking contribute to the amplification of senescence-inducing stresses, the avascular nature of IVD impairs the immune-clearance of the senescent disc cells, which accumulate in cell clusters, demonstrate inflammatory and catabolic phenotypes, deteriorate disc microenvironment, and accelerate IVDD. Anti-senescence strategies, including telomerase transduction, supply of growth factors, and blocking cell cycle inhibitors, have been shown to be feasible in rescuing disc cells from early senescence, but their efficiency for disc regeneration requires more in vivo validations. Guidelines dedicated to avoiding or alleviating senescence-inducing stresses might decelerate cellular senescence and benefit patients with IVD degenerative diseases.
Summary
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economically significant pathogen that has adversely affected China's swine industry. Currently, a novel type 2 PRRSV, ...called the NADC30‐like strain, is epidemic in numerous provinces of China, and commercial vaccines provide limited protection for infected animals. The extensive recombination phenomenon among NADC30‐like PRRSVs is identified as a unique molecular characteristic of the virus. However, our understanding of how recombination influences NADC30‐like PRRSVs is largely inadequate. In this study, we analysed the genetic characteristics of a recombinant NADC30‐like PRRSV (SC‐d) and examined its pathogenicity compared with a non‐recombinant NADC30‐like PRRSV (SD‐A19) and a highly pathogenic PRRSV (HuN4). SC‐d has three discontinuous deletions in nsp2, consistent with NADC30 isolated from the United States in 2008. Furthermore, we identified four recombination breakpoints in the SC‐d genome, which separated the SC‐d genome into four regions (regions A, B, C and D). Regions A and C are closely related to the JXA1‐like strain, one of the earliest Chinese HP‐PRRSV strains, and regions B and D are closely related to the NADC30 strain. Moreover, SC‐d inoculated piglets exhibited a persistent fever, moderate weight loss, mild thymus atrophy and obvious microscopic lung lesions. In summary, the recombinant NADC30‐like PRRSV SC‐d strain displayed a higher pathogenicity than the non‐recombinant NADC30‐like PRRSV SD‐A19 strain; however, the pathogenicity of the NADC30‐like PRRSV SC‐d was lower compared with the HP‐PRRSV HuN4 strain in piglets. Our findings demonstrate that recombination is responsible for the enormous genetic diversity and pathogenicity variance of the NADC30‐like PRRSV in China. This study provides a theoretical basis for developing a more reasonable PRRSV control and prevention strategy.
We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (mχ) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on ...time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in mχ are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σχNSI at 90% confidence level are derived as 2×10−32∼7×10−35 cm2 for TI analysis at mχ∼50–180 MeV/c2, and 3×10−32∼9×10−38 cm2 for AM analysis at mχ∼75 MeV/c2–3.0 GeV/c2.
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.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
This study is the first in a series of papers that aim to develop high-resolution emission databases for different anthropogenic sources in China. Here we focus on on-road transportation. Because of ...the increasing impact of on-road transportation on regional air quality, developing an accurate and high-resolution vehicle emission inventory is important for both the research community and air quality management. This work proposes a new inventory methodology to improve the spatial and temporal accuracy and resolution of vehicle emissions in China. We calculate, for the first time, the monthly vehicle emissions for 2008 in 2364 counties (an administrative unit one level lower than city) by developing a set of approaches to estimate vehicle stock and monthly emission factors at county-level, and technology distribution at provincial level. We then introduce allocation weights for the vehicle kilometers traveled to assign the county-level emissions onto 0.05° × 0.05° grids based on the China Digital Road-network Map (CDRM). The new methodology overcomes the common shortcomings of previous inventory methods, including neglecting the geographical differences between key parameters and using surrogates that are weakly related to vehicle activities to allocate vehicle emissions. The new method has great advantages over previous methods in depicting the spatial distribution characteristics of vehicle activities and emissions. This work provides a better understanding of the spatial representation of vehicle emissions in China and can benefit both air quality modeling and management with improved spatial accuracy.
We present results on light weakly interacting massive particle (WIMP) searches with annual modulation (AM) analysis on data from a 1-kg mass p-type point-contact germanium detector of the CDEX-1B ...experiment at the China Jinping Underground Laboratory. Datasets with a total live time of 3.2 yr within a 4.2-yr span are analyzed with analysis threshold of 250 eVee. Limits on WIMP-nucleus (χ-N) spin-independent cross sections as function of WIMP mass (m_{χ}) at 90% confidence level (C.L.) are derived using the dark matter halo model. Within the context of the standard halo model, the 90% C.L. allowed regions implied by the DAMA/LIBRA and CoGeNT AM-based analysis are excluded at >99.99% and 98% C.L., respectively. These results correspond to the best sensitivity at m_{χ}<6 GeV/c^{2} among WIMP AM measurements to date.
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.
Guangzhou, one of China's megacities, is beset with frequent occurrence of high-concentration ozone events. In this study, online instruments were used to simultaneously monitor ozone, nitrogen ...oxides (NOx) and volatile organic compounds (VOCs) at GPACS (the Guangzhou Panyu Atmospheric Composition Station) of the China Meteorological Administration, from June 2011 to May 2012, in order to determine their characteristics, the effect of VOCs on ozone photochemical production and the relationship between VOC / NOx ratio and ozone formation. The results showed that during the observation period, the seasonal variation of ozone concentration was lower in spring and winter compared to summer and autumn, which is opposite that for VOCs and NOx. In terms of VOCs, aromatics had the largest ozone formation potential, among which toluene, xylenes, ethylbenzene, 1,2,4-trimethylbenzene and 1,3,5-trimethylbenzene were the most important species, with a total contribution of about 44%. As the VOC / NOx ratios were very high during high-concentration ozone events that occur all year round, we speculate ozone production was likely to be NOx-limited regime (12:00-16:00 LT) in Guangzhou. Further investigation based on numerical models is needed in the future to obtain more detailed and robust conclusions.
Thermal energy storage is a necessary technology for the application of renewable energy and low-grade thermal energy. Chemical heat storage has been proved to be a feasible and promising method to ...store thermal energy. As compared to other thermal energy storage methods, chemical heat storage exhibits high energy storage density as well as feasibility for long-duration energy storage. In this paper, the basic principle of the chemical heat storage is firstly elaborated. Then the selection criteria of the chemical reaction are given. The aim of this review is to provide an insight into the promising candidate reactions for chemical heat storage application. The associated reversible chemical reactions available for thermal energy storage systems are summarized. Ongoing research and development studies illustrate that chemical heat storage is a very favorable option for the different application when diverse promising candidate reactions are selected. As working temperature is one of the key parameters for thermal energy storage systems, emphasis is given to the judgment of application temperature range for chemical heat storage. The determination of applicative temperature range of reversible chemical reactions is discussed. Besides, the challenge and prospect of the chemical heat storage technology are analyzed in the paper.
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