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.
The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various ...industrial applications, from actuators and medical devices to high-precision instruments
. The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys
-including gum metals
and strain glass alloys
-may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation
. Recently, chemically complex alloys, such as 'high-entropy' alloys
, have attracted tremendous research interest owing to their promising properties
. In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10
) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported.
Animal groups are often composed of individuals with differences in their phenotypes (e.g. body size, personality, or internal nutritional state). Such differences in phenotypes between group mates ...can have significant consequences for the collective movement and behavior of a group. Here, we examined the effects of nutritional state and ecological context on the individual‐ and group‐level behaviors of groups of shoaling goldfish (Carassius auratus) across an open water environment, an environment with food, and an environment with food and refuge. Fish were randomly manipulated to be in one of three nutritional states (control: fasted for 24 h, fasting: fasted for 1 week, and digestion: 2 h after feeding) and comprised five group compositions: the all‐control (6 control fish), all‐fasting (6 fasted fish), all‐digestion (6 digesting fish), mixed con–fas (3 control fish and 3 fasted fish), and mixed con–dig treatment (3 control fish and 3 digesting fish). We found that compared to the control and fasted treatments, the fish in the digestion treatment had lower individual swimming speeds and nearest neighbor distances. However, group polarization was lower in the fasted treatment than in both the control and digestion treatments. For the two mixed treatments, individual and collective behaviors of the fish seemed to be intermediate in comparison to those of either the fasted or digestion treatments. Moreover, group‐level differences in collective behaviors were maintained across different contexts. All five treatments exhibited considerable context‐associated changes in collective behaviors, but behavioral repeatability was dependent on the nutritional state of the group composition. Our results suggest that nutritional state and ecological context influence both individual and collective behaviors and that fasting and digestion exert opposite effects on collective behaviors across ecological contexts.
Animal groups are often composed of individuals with differences in their phenotypes (e.g., body size, personality, or internal nutritional state). Such differences in phenotypes between group mates can have significant consequences for the collective movement and behavior of a group. Here, we examined the effects of nutritional state and ecological context on the individual‐ and group‐level behaviors of groups of shoaling goldfish (Carassius auratus) across an open water environment, an environment with food, and an environment with food and refuge. Our results suggest that nutritional state and ecological context influence both individual and collective behaviors, and that fasting and digestion exert opposite effects on collective behaviors across ecological contexts.
•The interaction effects of roadway and weather attributes on freeway crashes are investigated.•A Bayesian spatio-temporal model is proposed for the investigation.•The results indicate significant ...interactions between several roadway and weather attributes.•The proposed model outperforms a random effect model and a spatial model.
This study attempts to examine the main and interaction effects of roadway and weather conditions on crash incidence, using the comprehensive crash, traffic and weather data from the Kaiyang Freeway in China in 2014. The dependent variable is monthly crash count on a roadway segment (with homogeneous horizontal and vertical profiles). A Bayesian spatio-temporal model is proposed to measure the association between crash frequency and possible risk factors including traffic composition, presence of curve and slope, weather conditions, and their interactions. The proposed model can also accommodate the unstructured random effect, and spatio-temporal correlation and interactions. Results of parameter estimation indicate that the interactions between wind speed and slope, between precipitation and curve, and between visibility and slope are significantly correlated to the increase in the freeway crash risk, while the interaction between precipitation and slope is significantly correlated to the reduction in the freeway crash risk, respectively. These findings are indicative of the design and implementation of real-time traffic management and control measures, e.g. variable message sign, that could mitigate the crash risk under the adverse weather conditions.
The disposal of contaminated plants limits the use of phytoremediation. Therefore, the disposal of contaminated sunflower was investigated after determining the phytoremediation of heavy metals under ...an oil crop rotation of sunflower (Helianthus annuus L)–sesame (Sesamum indicum L.). In the field experiment, the extraction efficiency of sunflower-sesame rotation was 0.07% for lead (Pb); 1.37% for zinc (Zn); 1.10% for copper (Cu); and 6.12% for cadmium (Cd). Contaminated sunflower stems were pyrolyzed at different temperature. The biochar produced at 300 °C was extracted in a two-step process (acid-extraction from biochar and metals precipitation in alkaline condition). At pH = 1, 65.67% of the Cd and much potassium (K) were extracted. After acid-extraction, adjust the pH of filtrate to 10, metals were precipitated and then separated from the K-enriched solution. Therefore, pyrolysis can process contaminated residues, and the biochar extracts can be reutilized as fertilizer to off-site crop production. Thus, an oil crop-rotation system, in addition to creating economic benefits, can be used by local farmers in contaminated soils.
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•Sunflowers and sesames have high tolerance against metal toxicity.•Sunflower-sesame rotation is a cost-effective for phytoremediation of heavy metal.•Low temperature biochar is a better choice to remain heavy metals and nutrients.•Two-step method provided a new idea for the utilization of heavy metal rich biochar.•Nutrients in biochar extracts can be used as fertilizer to off-site crop production.
To explore the clinical characteristics and prognosis of the new coronavirus 2019-nCoV patients combined with cardiovascular disease (CVD).
A retrospective analysis was performed on 112 COVID-19 ...patients with CVD admitted to the western district of Union Hospital in Wuhan, from January 20, 2020 to February 15, 2020. They were divided into critical group (ICU,
=16) and general group (
=96) according to the severity of the disease and patients were followed up to the clinical endpoint. The observation indicators included total blood count, C-reactive protein (CRP), arterial blood gas analysis, myocardial injury markers, coagulation function, liver and kidney function, electrolyte, procalcitonin (PCT), B-type natriuretic peptide (BNP), blood lipid, pulmonary CT and pathogen detection.
Compared with the general group, the lymphocyte count (0.74 (0.34, 0.94)×10
/L vs. 0.99 (0.71, 1.29)×10
/L,
=0.03) was extremely lower in the critical group, CRP (106.98 (81.57, 135.76) mg/L vs. 34.34 (9.55,76.54) mg/L,
<0.001) and PCT (0.20 (0.15,0.48) μg/L vs. 0.11 (0.06,0.20) μg/L,
<0.001) were significantly higher in the critical group. The BMI of the critical group was significantly higher than that of the general group (25.5 (23.0, 27.5) kg/m
vs. 22.0 (20.0, 24.0) kg/m
,
=0.003). Patients were further divided into non-survivor group (17, 15.18%) group and survivor group (95, 84.82%). Among the non-survivors, there were 88.24% (15/17) patients with BMI> 25.0 kg/m
, which was significantly higher than that of survivors (18.95% (18/95),
<0.001). Compared with the survived patients, oxygenation index (130 (102, 415) vs. 434 (410, 444),
<0.001) was significantly lower and lactic acid (1.70 (1.30, 3.00) mmol/L vs. 1.20 (1.10, 1.60) mmol/L,
<0.001) was significantly higher in the non-survivors. There was no significant difference in the proportion of ACEI/ARB medication between the critical group and the general group or between non-survivors and survivors (all
>0.05).
COVID-19 patients combined with CVD are associated with a higher risk of mortality. Critical patients are characterized with lower lymphocyte counts. Higher BMI are more often seen in critical patients and non-survivor. ACEI/ARB use does not affect the morbidity and mortality of COVID-19 combined with CVD. Aggravating causes of death include fulminant inflammation, lactic acid accumulation and thrombotic events.
This paper reviews the recent research and development of clay-based polymer nanocomposites. Clay minerals, due to their unique layered structure, rich intercalation chemistry and availability at low ...cost, are promising nanoparticle reinforcements for polymers to manufacture low-cost, lightweight and high performance nanocomposites. We introduce briefly the structure, properties and surface modification of clay minerals, followed by the processing and characterization techniques of polymer nanocomposites. The enhanced and novel properties of such nanocomposites are then discussed, including mechanical, thermal, barrier, electrical conductivity, biodegradability among others. In addition, their available commercial and potential applications in automotive, packaging, coating and pigment, electrical materials, and in particular biomedical fields are highlighted. Finally, the challenges for the future are discussed in terms of processing, characterization and the mechanisms governing the behaviour of these advanced materials.
The standard diagnosis of rotavirus gastroenteritis is based on the demonstration of rotavirus antigen in stools using an enzyme immunoassay (EIA). In this study, a one-step quantitative RT-PCR ...(Q-PCR) was used for sensitive detection of rotavirus in diarrheal stools. The primers and TaqMan probe for the Q-PCR were selected from a highly conserved region of the non-structural protein 3 (NSP3) of rotavirus. After validation, the test was applied to study rotavirus EIA positive (
N
=
25) and EIA negative (
N
=
143) stool specimens from cases of acute gastroenteritis of all degrees of severity in a prospective follow-up cohort of infants from 2 months to 2 years of age. Q-PCR detected all 25 EIA positive rotavirus antigens and seven additional cases that were rotavirus EIA negative, i.e. 28% more rotavirus positive cases than identified by EIA. It is concluded that Q-PCR using primers targeted at NSP3 is a rapid and sensitive method for diagnosing acute rotavirus gastroenteritis.
Polymer nanocomposites offer a wide range of promising applications because of their much enhanced properties arising from the reinforcement of nanoparticles. However, further development of such ...nanomaterials depends on the fundamental understanding of their hierarchical structures and behaviors which requires multiscale modeling and simulation strategies to provide seamless coupling among various length and time scales. In this review, we first introduce some computational methods that have been applied to polymer nanocomposites, covering from molecular scale (e.g., molecular dynamics, Monte Carlo), microscale (e.g., Brownian dynamics, dissipative particle dynamics, lattice Boltzmann, time-dependent Ginzburg–Landau method, dynamic density functional theory method) to mesoscale and macroscale (e.g., micromechanics, equivalent-continuum and self-similar approaches, finite element method). Then, we discuss in some detail their applications to various aspects of polymer nanocomposites, including the thermodynamics and kinetics of formation, molecular structure and dynamics, morphology, processing behaviors, and mechanical properties. Finally, we address the importance of multiscale simulation strategies in the understanding and predictive capabilities of polymer nanocomposites in which few studies have been reported. The present review aims to summarize the recent advances in the fundamental understanding of polymer nanocomposites reinforced by nanofillers (e.g., spherical nanoparticles, nanotubes, clay platelets) and stimulate further research in this area.
Highlights • We built a APP/PS1/nestin-GFP triple transgenic mouse model of Alzheimer’s disease. • The two main areas where neurogenesis was seen are the DG-SGZ and LV-SVZ. • AD temporally impairs ...hippocampal neurogenesis.