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Alzheimer’s Disease (AD), characterized by deficits in memory and cognition and by behavioral impairment, is a progressive neurodegenerative disorder that influences more than 47 million people worldwide. Currently, no available drug is able to stop AD progression. Therefore, novel therapeutic strategies need to be investigated.
We analyzed the RNA sequencing data (RNA-seq) derived from the Gene Expression Omnibus (GEO) database to identify the differentially expressed mRNAs in AD. The AD mouse model Tg2576 was used to verify the effects of IGF-2. The Morris Water Maze was administered to test the role of IGF-2 in memory consolidation. In addition, we quantified cell apoptosis by the TUNEL assay. The levels of amyloid plaques and the levels of Aβ40 and Aβ42 in the hippocampus were also determined by immunohistochemistry and ELISA, respectively.
RNA-seq analysis revealed that IGF-2 was remarkably reduced in AD. The expression of the upstream genes PI3K and AKT and the downstream gene CREB in the PI3K signaling pathway was significantly increased in the hippocampus of Tg2576 mice cells treated with IGF-2. The Morris water maze test showed that IGF-2 improved memory consolidation in Tg2576 mice. The activity of caspase-3 was decreased in Tg2576 mice treated with IGF-2. Amyloid plaques in the hippocampus were reduced, and the levels of Aβ40 and Aβ42 were decreased. The above effects of IGF-2 on AD were blocked when the PI3K signaling pathway inhibitor wortmannin was added.
IGF-2 attenuates memory decline, oxidative stress, cell apoptosis and amyloid plaques in the AD mouse model Tg2576 by activating the PI3K/AKT/CREB signaling pathway.
Late-life depression has become an important public health problem. Available evidence suggests that late-life depression is associated with all-cause and cardiovascular mortality among older adults living in the community, although the associations have not been comprehensively reviewed and quantified.
To estimate the pooled association of late-life depression with all-cause and cardiovascular mortality among community-dwelling older adults.
We conducted a systematic review and meta-analysis of prospective cohort studies that examine the associations of late-life depression with all-cause and cardiovascular mortality in community settings.
A total of 61 prospective cohort studies from 53 cohorts with 198 589 participants were included in the systematic review and meta-analysis. A total of 49 cohorts reported all-cause mortality and 15 cohorts reported cardiovascular mortality. Late-life depression was associated with increased risk of all-cause (risk ratio 1.34; 95% CI 1.27, 1.42) and cardiovascular mortality (risk ratio 1.31; 95% CI 1.20, 1.43). There was heterogeneity in results across studies and the magnitude of associations differed by age, gender, study location, follow-up duration and methods used to assess depression. The associations existed in different subgroups by age, gender, regions of studies, follow-up periods and assessment methods of late-life depression.
Late-life depression is associated with higher risk of both all-cause and cardiovascular mortality among community-dwelling elderly people. Future studies need to test the effectiveness of preventing depression among older adults as a way of reducing mortality in this population. Optimal treatment of late-life depression and its impact on mortality require further investigation.
Coal has fueled China's rapid growth in recent decades, but it also severely pollutes the air and causes many health issues. The magnitude of the health damage caused by air pollution depends on the location of emission sources. In this paper, we look into the spatial distribution of coal-fired power plants, which are the major emission sources in China, and investigate the determining factors behind the distribution. We find that the driving factors are economic development and expansion of electricity grid coverage; the latter factor plays a key role in provinces that are less developed but have abundant coal resources. This suggests a way to reduce health damages caused by air pollution without harming the economy: attracting coal-fired plants to less populated areas by developing trans-province electricity trade and grid coverage.
The mass-balance of Muztag Ata No. 15 (MZ15) glacier in the eastern Pamir is reconstructed between 1980 and 2012 using an energy-based mass-balance model. The results show that this glacier has been characterized by obvious interannual mass-balance changes during 1980–2012 with a slightly positive mass balance during 1998–2012. Precipitation in the ablation season is a primary driver of these mass-balance fluctuations. Distinct changes in the mass-balance of MZ15 glacier between 1980–1997 and 1998–2012 are thought to be associated with changes in the regionally averaged meridional wind speed and corresponding precipitation in the ablation season. The negative and positive mass-balance phases during 1980–1997 and 1998–2012, respectively, were associated with northerly and southerly wind anomalies in the eastern Pamir and their corresponding decreasing and increasing precipitation. These changes in circulation appear to be linked to the mid-latitude climate. Finally, contrary to the variation of most glaciers on the Tibetan Plateau, glaciers in the Karakoram-western Kunlun-eastern Pamir appear to have retreated more slowly over the past 10 years than during the 1970s-2000. This contrasting trend may be caused by different changes in snowfall and different topography factors in different regions under warming and increased precipitation.
Paradoxical arguments and mixed empirical evidence coexist in the current literature concerning the relationship between team familiarity and team innovation. To resolve this contradiction, we apply habitual routines theory to propose that team familiarity and team innovation have an inverted U-shaped relationship. Using a data set of 68,933 R&D teams in the electrical engineering industry, our results support a nonlinear relationship between team familiarity and team innovation, and suggest that the best innovative performance is produced by moderately familiar teams. Furthermore, we find that external learning can moderate this curvilinear relationship. Theoretical contributions and future implications are discussed.
The neuropsychological origins of negative syndrome of schizophrenia remain elusive. Evidence from behavioural studies, which utilised emotion-inducing pictures to elicit motivated behaviour generally reported that that schizophrenia patients experienced similar affective experience as healthy individuals but failed to translate emotional salience to motivated behaviour, a phenomenon called emotion–behaviour decoupling. However, a few studies have examined emotion–behaviour decoupling in non-psychotic high-risk populations, who are relatively unaffected by medication effects.
In this study, we examined the nature and extent of emotion–behaviour decoupling in in three independent samples (65 schizophrenia patients v. 63 controls; 40 unaffected relatives v. 45 controls; and 32 individuals with social anhedonia v. 32 controls). We administered an experimental task to examine their affective experience and its coupling with behaviour, using emotion-inducing slides, and allowed participants to alter stimulus exposure using button-pressing to seek pleasure or avoid aversion.
Schizophrenia patients reported similar affective experiences as their controls, while their unaffected relatives and individuals with high levels of social anhedonia exhibited attenuated affective experiences, in particular in the arousal aspect. Compared with their respective control groups, all of the three groups showed emotion–behaviour decoupling.
Our findings support that both genetically and behaviourally high-risk groups exhibit emotion–behaviour decoupling. The familial association apparently supports its role as a putative trait marker for schizophrenia.
We report on the radiative transfer process and optical properties of sea ice in the thermal infrared (TIR) band, presenting two new linear kernel driver models (Relative Emissivity Distribution Function, REDF) that describe TIR emission characteristics of smooth and rough ice. In order to test the models and determine the necessary coefficients, in situ measurements from the Bohai Sea were carried out during the 2011/12 and 2012/13 boreal winters. The results show that the relative emissivity of smooth sea ice decreases along with increasing viewing zenith angle, and the shape of the relative emissivity curve is similar to that of an ideal plane. Affected by parameters such as roughness and surface temperature distribution, the anisotropy of relative emissivity of sea ice with a high degree of roughness is stronger relative to the cosine emitter. The model coefficients were also obtained using a robust regression method based on the measured data. The presented models are more practical than the numerical radiative transfer model and can be used for multi-angular TIR remote sensing.
It is important to fabricate iron-based nitride/conductive material composite to obtain good catalytic performance. In this work, Fe2N nanoparticles with diameter of approximately 30 nm have been successfully dispersed on the surface of nitrogen-doped graphite oxide (NrGO) by a facile sol–gel method and further ammonia atmosphere treatment. XPS, XRD, Raman, and TEM proved that Fe2N nanoparticles are well monodispersed, and nitrogen atoms are doped in NrGO. The composite possessed two merits, that is, the more catalytic active site in Fe2N nanoparticles due to the well monodispersion, and fast electron transfer due to the nitrogen dope in rGO. With the proper ratio, the composite exhibited brilliant catalytic activity and durability in acidic media. It possesses overpotential of 94 mV to approach 10 mA/cm2, a small Tefel slope of 49 mV/dec, and maintains the good electrocatalytic activity for 10 h. Cyclic voltammetry and electrochemical impedance spectroscopy indicated that the electrocatalyst possessed high catalytic active area and fast electron transfer. Our work may provide a new avenue for the preparation of low-cost iron-based nitride/NrGO composite for highly efficient electrochemical hydrogen evolution.
Tungstate based phosphors have efficient absorption in the UV region and can be used for UV-pumped light emitting. For novel and effective materials and synthesis methods in this system, a series of Eu3+ and Tb3+ co-doped NaY(WO4)2 phosphors have been synthesized via the molten salt method. The powder X-ray diffraction (PXRD) patterns, scanning electronic microscope (SEM), and photoluminescent spectra have been characterized for the prepared samples. The results show the flux (NaCl) not only decreases the reaction temperature (700–900 °C) than the normal solid state synthesis (∼1000 °C), but also controls the morphology of the products. The shape and size of products can be changed simply and effectively by the reaction conditions, such as temperature and heating time. It is also found that the emission colors of the samples can be tuned from red to green by simply adjusting the doping concentrations of Eu3+ and Tb3+ ions under the same wave length excitation, which has potential applications for multi-color display and illumination as a single-component phosphor.
Although there has been considerable computer-aided conceptual design research, most of the proposed approaches are domain specific and can merely achieve conceptual design of energy flows-processing systems. Therefore, this research is devoted to the development of a general (i.e., domain-independent) and knowledge-based methodology that can search in a wide multidisciplinary solution space for suitable solution principles for desired material-flow processing functions without designers' biases toward familiar solution principles. It first proposes an ontology-based approach for representing desired material-flow processing functions in a formal and unambiguous manner. Then a rule-based approach is proposed to represent the functional knowledge of a known solution principle in a general and flexible manner. Thereafter, a simulation-based retrieval approach is developed, which can search for suitable solution principles for desired material-flow processing functions. The proposed approaches have been implemented as a computer-aided conceptual design system for test. The conceptual design of a coin-sorting device demonstrates that our functional representation methodology can make the proposed computer-aided conceptual design system to effectively and precisely retrieve suitable solution principles for a desired material-flow processing function.
Novel mixed micelle was successfully fabricated by the synergistic self-assembly of poly(methacrylate isobutyl polyhedral oligomeric silsesquioxane (POSS)-co-N-isopropylacrylamide-co-oligo(ethylene glycol)methyl ether methacrylate-co-acrylic acid) (P(methacrylate isobutyl (MAPOSS)-co-NIPAM-co-OEGMA-co-AA)) and poly(methacrylate isobutyl POSS-co-N-isopropylacrylamide-co-oligo(ethylene glycol) methyl ether methacrylate-co-2-vinylpyridine) (P(MAPOSS-co-NIPAM-co-OEGMA-co-2VP)). Dynamic light scattering (DLS) and transmission electron microscopy characterizations demonstrate that the formation of mixed micelles is driven by electrostatic interaction. The formation of the mixed micelles was further implied by a simple fluorescence resonance energy transfer based technique. The mixed micelle possesses the biggest size at pH = 7.0, which is attributed to the strongest electrostatic interaction between the two kinds of micelles. The zeta potential under different pH was detected to further investigate the surface charges corroborating the discussions. DLS and UV-vis indicate that the lower critical solution temperature (LCST) is pH dependent. The mixed micelles reach the highest LCST at pH 7.0. The LCST of the mixed micelle can be tuned by adjusting the volume ratio of the two kinds of micelles as well. Moreover, the thermo-responsive behavior of the mixed micelle is absolutely reversible.
Most long QT syndrome patients are associated with genetic mutations. We aimed to investigate the clinical and biochemical characteristics and look for genotype-based preventive implications in Chinese long QT syndrome patients.
Methods and results
We identified two missense mutations of the KCNQ1 gene in two independent Chinese families, including a previously reported mutation R380S in the C-terminus and a novel mutation W305L in the P-loop domain of the Kv7.1 channel, respectively. The proband with R380S was an 11-year-old girl who suffered a prolonged corrected QT interval of 660 ms, recurrent syncope, and sudden cardiac death, whose father was an asymptomatic carrier. The mutation W305L was detected in a 36-year-old woman with long QT syndrome and her immediate family members including the proband’s younger sister with an unexplained syncope, her son, and her elder daughter without symptoms. Metoprolol appeared to be effective in preventing arrhythmias and syncope in long QT syndrome patients with mutation W305L. Both R380S and W305L mutations led to “loss-of-function” of the Kv7.1 channel accounting for the clinical phenotypes.
We first show two missense KCNQ1 mutations – R380S and W305L – in Chinese long QT syndrome patients, resulting in the loss of protein function. Mutation W305L in the P-loop domain of the Kv7.1 may derive a pronounced benefit from β-blocker therapy in symptomatic long QT syndrome patients, whereas mutation R380S located in the C-terminus may be associated with a high risk of sudden cardiac death.
In this study, a novel hybrid block copolymer containing POSS (BCP), poly(methacrylisobutyl-POSS)-b-poly(methylmethacrylate) (PMAiBuPOSS-b-PMMA) was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The structure and molecular weight were characterized via 1H NMR and GPC. BCP was creatively used as the compatibilizer to overcome the bad compatibility of epoxy and POSS in their blend system. SEM and dynamic mechanical thermal analyses (DMTA) were used to observe the surface morphology and thermal–mechanical behaviors of the resultant products. We found that the amount of microaggregation domains of POSS decreased, while the nano ones increased, when BCP content increased. All the aggregation domains were distributed in epoxy matrix uniformly at nanoscale with the addition of 10 phr BCP and 5 phr POSS monomers. The results indicated that BCP could effectively improve the compatibility between epoxy resin and POSS owing to its amphiphilicity in DGEBA. The fracture behavior of products transformed from brittle fracture to ductile fracture gradually with the increase of BCP, whereas the Tg and E′ decreased.
To examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city.
An intervention trial.
Shenzhen City, Guangdong Province, China.
From a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18–69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks.
For the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men.
For obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.
The aluminothermic reduction and nitridation method using microsized Al powder and nanosized alumina powder was employed to fabricate AlON powder under N2 atmosphere. Single-phase aluminum oxynitride (AlON) can be prepared at a relatively low temperature (1700 °C) with a holding time of 3 h. The powder is ball milled, doped with different amounts of Y2O3 (0.1–0.9 wt%) as a sintering additive, and then shaped into pellets. The pellet sintering is carried out at two relatively low temperatures (1860 and 1880 °C) for 10 h. The transmittance and hardness of the obtained samples varies as the amount of Y2O3 varies. The sample sintered under optimal conditions can reach an ultimate transmittance of 65% with 2 mm thickness. The Vickers hardness of highly transparent AlON ceramic is about 15.95 ± 0.17 GPa, indicating that our method has a promising future in transparent AlON ceramic production. The sintering promoting mechanisms of Y2O3 are also discussed in detail.
The fabrication of Ce3+-doped lutetium oxyorthosilicate (Lu2SiO5:Ce, LSO:Ce) scintillation ceramics was investigated by pressureless sintering starting from synthetic submicrometer polycrystalline LSO:Ce powder. It was found that translucent LSO ceramics were densified successfully with relative density of 99.5% under sintering condition of 1720 °C for 4 h. As-sintered LSO ceramics were pore-free with average grain size of 5 μm and exhibited a translucent state. The broad emission spectra centered at 419 nm of the LSO:Ce ceramics under vacuum ultraviolet (VUV) and UV excitation at room temperature. Under x-ray excitation, the overall emission intensity of obtained LSO ceramics achieved twice of that of bismuth germanium oxide (also known as bismuth germanate) single crystal at room temperature. Under excitation of 356 nm and emission of 420 nm, the luminescence decay time of the obtained LSO scintillation ceramics reached only 21.2 ns. The light yield of the LSO ceramics was 21,300 ph/MeV, which reached 91% of that of LSO single crystal.
Multiferroic CoFe2O4–BiFeO3 (CFO–BFO) core–shell nanofibers were synthesized by coaxial electrospinning. The spinel structure of CFO and perovskite structure of BFO were confirmed by x-ray diffraction and high-resolution transmission electron microscopy. The core–shell configuration of nanofibers was verified by scanning electron microscopy and transmission electron microscopy images. The macroscopic ferromagnetic property of core–shell nanofibers was demonstrated by magnetic hysteresis loop. The local magnetoelectric (ME) coupling was confirmed by using dual frequency piezoresponse force microscopy (PFM) under an external magnetic field, showing magnetically induced evolution of piezoresponse and domain structure. The ferroelectric characteristics are demonstrated by the switching spectroscopy PFM. From PFM hysteresis and butterfly loops, it is observed that the piezoresponse amplitude is reduced while coercive voltage increased under external in-plane magnetic field, induced through the mechanical interactions between magnetostrictive CFO and piezoelectric BFO, from which the lateral ME coupling can be estimated quantitatively. The nanofibers thus can find a variety of applications as a one-dimensional multiferroic material.
This work presents the preparation and characterization of N-doped TiO2 nanocrystals obtained by a solid-state reaction in vacuum with urea as the nitrogen source. The particle sizes of the products are smaller than 20 nm from the x-ray powder diffraction patterns and the transmission electron microscopy images. Different from the reported samples obtained in air or under dry N2 or NH3 gas flow, the doped nitrogen exists mainly as absorbed NOx groups but as smaller incorporated species in the nanocrystals, which is supported by the results from x-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and ultraviolet–visible diffuse reflectance spectroscopy. Dependent on the nitrogen amount, the surface photovoltage (SPV) response reaches the maximum at the mediate molar ratio of 5:4 (urea to TiO2), which can be explained that proper nitrogen concentration can enhance the separation of the photogenerated carriers to improve the SPV intensity, but excess nitrogen can spread the impurity energy levels to narrow energy gaps, which reinforces the combination of the photogenerated electrons and holes and then decreases the SPV signal. The corresponding detailed discussion is also reported.