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Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.
Aims
By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.
Method
Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.
Results
Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.
Conclusions
This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.
This study presents a dual-channel vortex generator (VG) that leverages the snap-through behaviour of flexible sheets. The VG outperforms a similar-sized rigid VG in generating vortices within dual-channel flows while minimizing pressure loss. Numerical simulations using the immersed boundary-lattice Boltzmann method analyse the dynamics and vortex generation performance of the sheet under various system parameters. Two distinct modes are identified for the elastic sheet: a sustained snap-through mode (SSTM) and a dormant mode (DM). The sheet's mode is predominantly influenced by its length ratio (L*), bending stiffness $(K_b^\ast )$ and flow strength, with the mass ratio having a minimal impact. The sheet exhibiting regular SSTM can effectively generate vortices in both channels and the vortex generation performance can be conveniently tuned by altering the sheet's initial buckling (i.e. L*). An increase in $K_b^\ast $ results in a higher critical Reynolds number (Rec) required for mode transition. An increase in L*, however, initially raises Rec and then lowers it, suggesting an optimal length ratio (approximately 0.7 for our considered system) for minimizing the Rec necessary to trigger SSTM. Furthermore, a disparity in the flow strength between channels is found to suppress the snap-through of the sheet; a greater disparity, however, is permissible to induce the SSTM of more compliant sheets. These findings underscore the potential of snap-through behaviour for enhanced flow manipulation in dual-channel systems.
Mythimna separata (Lepidoptera: Noctuidae) is an omnivorous pest that poses a great threat to food security. Insect antimicrobial peptides (AMPs) are small peptides that are important effector molecules of innate immunity. Here, we investigated the role of the AMP cecropin B in the growth, development, and immunity of M. separata. The gene encoding M. separata cecropin B (MscecropinB) was cloned. The expression of MscecropinB was determined in different developmental stages and tissues of M. separata. It was highest in the prepupal stage, followed by the pupal stage. Among larval stages, the highest expression was observed in the fourth instar. Tissue expression analysis of fourth instar larvae showed that MscecropinB was highly expressed in the fat body and haemolymph. An increase in population density led to upregulation of MscecropinB expression. MscecropinB expression was also upregulated by the infection of third and fourth instar M. separata with Beauveria bassiana or Bacillus thuringiensis (Bt). RNA interference (RNAi) targeting MscecropinB inhibited the emergence rate and fecundity of M. separata, and resulted in an increased sensitivity to B. bassiana and Bt. The mortality of M. separata larvae was significantly higher in pathogen plus RNAi-treated M. separata than in controls treated with pathogens only. Our findings indicate that MscecropinB functions in the eclosion and fecundity of M. separata and plays an important role in resistance to infection by B. bassiana and Bt.
Cognitive control deficits are one of the main symptoms of psychosis. The basic neural oscillation patterns associated with cognitive control are already present in early adolescence. However, as previous studies have focused on adults with psychosis, it is unclear whether neurobiological impairments in cognitive control are present in children and adolescents with first-episode psychosis (FEP) or clinical high-risk (CHR) state for psychosis.
Aims
To explore the deficits of electroencephalogram related to cognitive control tasks in children and adolescents with FEP and CHR.
Method
Electroencephalogram was recorded in untreated 48 patients with FEP, 24 patients with CHR and 42 healthy controls aged 10–17 years, while performing the visual oddball task. The N2 amplitude, theta and alpha oscillations were then analysed and compared between groups.
Results
There was no significant group difference in N2 amplitude (P = 0.099). All groups showed increased theta and alpha oscillations relative to baseline before the stimulus in the frontal, central, left fronto-central and right fronto-central areas. These changes differed significantly between groups, with the FEP group showing significantly smaller theta (P < 0.001) and alpha (P < 0.01) oscillation than healthy controls. Theta and alpha oscillations in the CHR group did not differ significantly from the FEP group and healthy controls.
Conclusions
These results suggest that neural damage has already occurred in the early stage of psychosis, and that abnormal rhythmic activity of neurons may constitute the pathophysiological mechanism of cognitive dysfunction related to early-onset psychosis.
Brain ageing, the primary risk factor for cognitive impairment, occurs because of the accumulation of age-related neuropathologies. Identifying effective nutrients that increase cognitive function may help maintain brain health. Tomatoes and lemons have various bioactive functions and exert protective effects against oxidative stress, ageing and cancer. Moreover, they have been shown to enhance cognitive function. In the present study, we aimed to investigate the effects of tomato and lemon ethanolic extracts (TEE and LEE, respectively) and their possible synergistic effects on the enhancement of cognitive function and neurogenesis in aged mice. The molecular mechanisms underlying the synergistic effect of TEE and LEE were investigated. For the in vivo experiment, TEE, LEE or their mixture was orally administered to 12-month-old mice for 9 weeks. A single administration of either TEE or LEE improved cognitive function and neurogenesis in aged mice to some extent, as determined using the novel object recognition test and doublecortin immunohistochemical staining, respectively. However, a significant enhancement of cognitive function and neurogenesis in aged mice was observed after the administration of the TEE + LEE mixture, which had a synergistic effect. N-methyl-d-aspartate receptor 2B, postsynaptic density protein 95, and brain-derived neurotrophic factor (BDNF) levels and tropomyosin receptor kinase B (TrkB)/extracellular signal-regulated kinase (ERK) phosphorylation also synergistically increased after the administration of the mixture compared with those in the individual treatments. In conclusion, compared with their separate treatments, treatment with the TEE + LEE mixture synergistically improved the cognitive function, neurogenesis and synaptic plasticity in aged mice via the BDNF/TrkB/ERK signalling pathway.
The land cover of the Sanjiang Plain has changed dramatically since the 1950s. Although previous studies have analysed its spatiotemporal dynamics at long time intervals, a near real-time and accurate representation of the interannual evolution of cropping patterns in this region is of far-reaching importance for rationally allocating agricultural resources and ensuring food security. Based on the 30 m and 10 m land cover datasets in 2015 and 2017–2019, the current study used Landsat-8 satellite data in 2014, 2016 and 2020 to identify paddy rice and dryland crops using a decision tree classification approach and constructed the annual cropland datasets of the Sanjiang Plain from 2014 to 2020. The results show that the overall classification accuracies of crop datasets exceeded 95%, and the Kappa coefficients were higher than 0.92. The average annual accuracies of users and producers were 93% and 94% for rice fields and 97% and 95% for dryland crops, respectively. During the 7 years, the total area of paddy fields and dryland crops decreased by 5% and 8%. However, with minor positive and negative variation between years. 24.2% of paddy rice and 42% of dryland crops has been cultivated under 4 years. The centres of gravity for both crops mainly aggregated in the central counties with the migration direction and magnitude varying interannually. The current study emphasizes the importance of establishing annual high-resolution crop datasets to track the detailed spatio-temporal trajectories of cropping patterns that are essential to support sustainable cropland management and agricultural development.
We report VLBI monitoring observations of the 22 GHz H2O masers toward the Mira variable BX Cam. Data from 37 epochs spanning ∼3 stellar pulsation periods were obtained between May 2018 and June 2021 with a time interval of 3–4 weeks. In particular, the VERA dual-beam system was used to measure the kinematics and parallaxes of the H2O maser features. The obtained parallax, 1.79±0.08 mas, is consistent with Gaia EDR3 and previous VLBI measurements. The position of the central star was estimated relied on Gaia EDR3 data and the center position of the 43 GHz SiO maser ring imaged with KVN. Analysis of the 3D maser kinematics revealed an expanding circumstellar envelope with a velocity of 13±4 km s−1 and significant spatial and velocity asymmetries. The H2O maser animation achieved by our dense monitoring program manifests the propagation of shock waves in the circumstellar envelope of BX Cam.
This paper focuses on configuration design, dimensional synthesis, and engineering application of a novel asymmetric 2R1T parallel mechanism (PM) with zero-coupling degree. The analytical forward and inverse displacement solutions are deduced by the means of vector method. The mathematical models between Euler angles and the orientational parameters (i.e., azimuth and tilt angles) of the offset output axis are established. Using screw theory as mathematical tool, this paper worked out evaluation indices of motion/force transmissibility and presented the definitions and calculation methods of good transmission orientation workspace and good transmission orientation capacity (GTOC). Furthermore, a comparative example with respect to kinematic performance of asymmetric UPS-RPU-PU PM and planar symmetric 2UPS-PU PM is carried out, and the result demonstrates that UPS-RPU-PU significantly outperforms 2UPS-PU in terms of GTOC. The constrained optimization model is constructed to formulate optimal problem of dimensional parameters on the maximizing GTOC, which is then solved by differential evolution algorithm. Finally, an engineering case demonstrates that the optimized mechanism has a good application prospect in hydraulic support test bed.
In light of the dynamic systems perspective, the current study expanded existing literature by examining the moderating effect of maternal sensitivity on the quadratic association between infant negative reactivity and future executive function development. Using a longitudinal, multimethod design, we addressed executive function development among preschoolers. This study utilized data from the Family Life Project (N = 1292). Infant negative reactivity at 6 months, maternal sensitivity across first 3 years, and executive functions during preschool age were observational assessed. A path model with moderation analyses revealed a U-shaped quadratic association between infant negative reactivity and preschoolers’ inhibitory control, only when maternal sensitivity was high. The results suggest that maternal sensitivity may assist infants with both low and high, but not moderate, levels of negative reactivity towards better executive function development. Findings support the ongoing nonlinear person-environment interplay during early years of life.
As city residents eat out more frequently, it is unknown that if iodised salt is still required in home cooking. We analysed the relationship of household salt and eating out on urinary iodine concentration (UIC) in pregnant women. A household condiment weighing method was implemented to collect salt data for a week. A household salt sample was collected. A urine sample was taken at the end of the week. Totally, 4640 participants were investigated. The median UIC was 139·1 μg/l in pregnant women and 148·7, 140·0 and 122·9 μg/l in the first, second and third trimesters. Median UIC in the third trimester was lower than in the other trimesters (P < 0·001). The usage rates of iodised (an iodine content ≥ 5·0 mg/kg) and qualified-iodised (an iodine content ≥ 21·0 mg/kg) salt were 73·9 and 59·3 %. The median UIC in the qualified-iodised salt group was higher than in the non-iodised group (P = 0·037). The median UIC in the non-iodised group who did not eat out was lower than in qualified-salt groups who both did and did not eat out (P = 0·007, <0·001). The proportion of qualified-iodised salt used in home cooking is low, but foods eaten out have universal salt iodisation according to the national compulsory policy. Household iodised salt did not play a decisive role in the iodine status of pregnant women. Pregnant women in their third trimester who are not eating out and using non-iodised salt at home require extra iodine.
A novel solid-clad-by-liquid method was developed to form a 10-m long by 10-mm wide by 80-μm thick Ni–5 at.% W/Ni–9.3 at.% W/Ni–5 at.% W composite tape. Three deformation routes (cold rolling, cold rolling with intermediate annealing, and cold rolling combined with warm rolling) have been investigated in short Ni–5 at.% W/Ni–9.3 at.% W/Ni–5 at.% W composite substrate. To optimize the dynamic continuous annealing parameters for the long composite substrates, air-cooled and furnace-cooled annealing procedures were compared in short Ni–5 at.% W/Ni–9.3 at.% W/Ni–5 at.% W composite substrates. Improved cube texture of 98.7% in a 10-m long by 10-mm wide by 80-μm thick Ni–5 at.% W/Ni–9.3 at.% W/Ni–5 at.% W composite substrate was achieved via warm rolling deformation at 550 °C and two-step dynamic continuous annealing (750 °C for 1 h followed by 1200 °C for 1 h). The yield strength, Curie temperature, and saturation magnetization of 176 MPa, 324 K, and 18 emu/g, respectively, were obtained.
A new linear and conservative finite difference scheme which preserves discrete mass and energy is developed for the two-dimensional Gross–Pitaevskii equation with angular momentum rotation. In addition to the energy estimate method and mathematical induction, we use the lifting technique as well as some well-known inequalities to establish the optimal $H^{1}$-error estimate for the proposed scheme with no restrictions on the grid ratio. Unlike the existing numerical solutions which are of second-order accuracy at the most, the convergence rate of the numerical solution is proved to be of order $O(h^{4}+\unicode[STIX]{x1D70F}^{2})$ with time step $\unicode[STIX]{x1D70F}$ and mesh size $h$. Numerical experiments have been carried out to show the efficiency and accuracy of our new method.
We examined the in vitro developmental competence of parthenogenetic activation (PA) oocytes activated by an electric pulse (EP) and treated with various concentrations of AZD5438 for 4 h. Treatment with 10 µM AZD5438 for 4 h significantly improved the blastocyst formation rate of PA oocytes in comparison with 0, 20, or 50 µM AZD5438 treatment (46.4% vs. 34.5%, 32.3%, and 24.0%, respectively; P < 0.05). The blastocyst formation rate was higher in the group treated with AZD5438 for 4 h than in the groups treated with AZD5438 for 2 or 6 h (42.8% vs. 38.6% and 37.2%, respectively; P > 0.05). Furthermore, 66.67% of blastocysts derived from these AZD5438-treated PA oocytes had a diploid karyotype. The blastocyst formation rate of PA and somatic cell nuclear transfer (SCNT) embryos was similar between oocytes activated by an EP and treated with 2 mM 6-dimethylaminopurine for 4 h and those activated by an EP and treated with 10 µM AZD5438 for 4 h (11.11% vs. 13.40%, P > 0.05). In addition, the level of maturation-promoting factor (MPF) was significantly decreased in oocytes activated by an EP and treated with 10 µM AZD5438 for 4 h. Finally, the mRNA expression levels of apoptosis-related genes (Bax and Bcl-2) and pluripotency-related genes (Oct4, Nanog, and Sox2) were checked by RT-PCR; however, there were no differences between the AZD5438-treated and non-treated control groups. Our results demonstrate that porcine oocyte activation via an EP in combination with AZD5438 treatment can lead to a high blastocyst formation rate in PA and SCNT experiments.
The microstructural evolution of spray-formed high speed steel during hot deformation was investigated as well as the effects of spray forming parameters on the porosity formation. Four distinct zones are identified in the as-deposited material, and interstitial porosity is present in the bottom and peripheral zones, while gas-related porosity is mainly found in the central zone. It can keep the porosity at a minimum value by using the optimum parameters, e.g., the average porosity of central zone is 3.7% for a superheat of 170 °C and a gas-to-metal flow rate of 0.7. During hot deformation at 1150 °C, the amount of porosity can be obviously decreased by increasing the height reduction which also plays a key role in breaking up eutectic carbides. The critical height reduction for the breakdown of the eutectic carbides is 50%, the dominant mechanism being mechanical fragmentation.
In this paper the Grid correction method (GRID) was proposed for the first time as an interpolation method of the double differenced ionospheric delay for GNSS Network RTK. The Distance Interpolation Method (DIM), Linear Interpolation Method (LIM), the Kriging Interpolation Method (KRG) and the GRID are described and compared in the aspect of their interpolation performance. It was shown in the tests that the GRID interpolation method performed better than the other three. For mid-latitude stations, its interpolation accuracy is better than 1 cm, and the extrapolation accuracy is better than 2 cm. Furthermore, the GRID method can achieve a good performance even at low satellite elevation, and also its interpolation accuracy can be better than 2 cm at low latitudes.
We conducted community interviews and field surveys to determine the distribution and population of the Endangered Shortridge's capped langur Trachypithecus shortridgei, and the threats to the species, in the Dulong and Nu River valleys of north-western Yunnan Province, China. We found that c. 19 groups of T. shortridgei reside in the Dulong valley, mostly located in the southern portion of the valley. According to interview and observational records in the Gaoligong Mountains to the west of the Nu River, 12 individuals and no groups were observed. Family groups consist of one adult male, 2–3 adult females and up to five young. We estimate the population of T. shortridgei in China to be c. 250–370 individuals. Threats to the species include habitat loss and poaching. We suggest several measures to conserve T. shortridgei, such as a review of the Gaoligong National Nature Reserve management strategy, and increasing engagement, education, inclusion of local people in forest management, and the consistency of enforcement.
Few studies have explored the relationship between dietary patterns and the risk of gestational diabetes mellitus (GDM). Evidence from non-Western areas is particularly lacking. In the present study, we aimed to examine the associations between dietary patterns and the risk of GDM in a Chinese population. A total of 3063 pregnant Chinese women from an ongoing prospective cohort study were included. Data on dietary intake were collected using a FFQ at 24–27 weeks of gestation. GDM was diagnosed using a 75 g, 2 h oral glucose tolerance test. Dietary patterns were determined by principal components factor analysis. A log-binomial regression model was used to examine the associations between dietary pattern and the risk of GDM. The analysis identified four dietary patterns: vegetable pattern; protein-rich pattern; prudent pattern; sweets and seafood pattern. Multivariate analysis showed that the highest tertile of the vegetable pattern was associated with a decreased risk of GDM (relative risk (RR) 0·79, 95 % CI 0·64, 0·97), compared with the lowest tertile, whereas the highest tertile of the sweets and seafood pattern was associated with an increased risk of GDM (RR 1·23, 95 % CI 1·02, 1·49). No significant association was found for either the protein-rich or the prudent pattern. The protective effect of a high vegetable pattern score was more evident among women who had a family history of diabetes (P for interaction = 0·022). These findings suggest that the vegetable pattern was associated with a decreased risk of GDM, while the sweets and seafood pattern was associated with an increased risk of GDM. These findings may be useful in dietary counselling during pregnancy.
The mitochondrial genome is maternally inherited in animals, despite the fact that paternal mitochondria enter oocytes during fertilization. Autophagy and ubiquitin-mediated degradation are responsible for the elimination of paternal mitochondria in Caenorhabditis elegans; however, the involvement of these two processes in the degradation of paternal mitochondria in mammals is not well understood. We investigated the localization patterns of light chain 3 (LC3) and ubiquitin in mouse and porcine embryos during preimplantation development. We found that LC3 and ubiquitin localized to the spermatozoon midpiece at 3 h post-fertilization, and that both proteins were colocalized with paternal mitochondria and removed upon fertilization during the 4-cell stage in mouse and the zygote stage in porcine embryos. Sporadic paternal mitochondria were present beyond the morula stage in the mouse, and paternal mitochondria were restricted to one blastomere of 4-cell embryos. An autophagy inhibitor, 3-methyladenine (3-MA), did not affect the distribution of paternal mitochondria compared with the positive control, while an autophagy inducer, rapamycin, accelerated the removal of paternal mitochondria compared with the control. After the intracytoplasmic injection of intact spermatozoon into mouse oocytes, LC3 and ubiquitin localized to the spermatozoon midpiece, but remnants of undegraded paternal mitochondria were retained until the blastocyst stage. Our results show that paternal mitochondria colocalize with autophagy receptors and ubiquitin and are removed after in vitro fertilization, but some remnants of sperm mitochondrial sheath may persist up to morula stage after intracytoplasmic spermatozoon injection (ICSI).
Gold–silver (Au–Ag) bimetal dispersed SiO2 composite films were fabricated via a chemical solution approach combining sol–gel with a spin-coating process, and they were investigated by transmission electron microscopy (TEM), x-ray photoelectron spectroscopy (XPS), and ultraviolet-visible absorption spectra. TEM image indicated that Ag and/or Au nanoparticles (NPs) had a spherical structure with large size distributions. The XPS results demonstrated that the presence of both Ag and Au NPs in the composite film is in each metal state. The optical absorption spectra of the composite film further confirmed the formation of nanosized Au and Ag particles, given by the two surface plasmon resonance (SPR) peaks. Unlike other Au–Ag composite films, these two SPR peaks had almost the same intensity, which is rarely obtained by a chemical approach. Compared to optical absorption spectra calculated by the modified Mie theory, the location and intensity of SPR peaks had a little difference, which could be attributed to large size distributions of Ag and Au bimetal NPs in the composite film along with the experimental process. In addition, the intensity of both SPR peaks was content-related.
Ag nanoparticles dispersed SiO2 composite films were successfully prepared by a sol–gel method. The structural transition, formation, and optical property along with relevant band gap of Ag/SiO2 thin films during the annealing process were studied by Fourier transform infrared spectroscopy, thermogravimetry–differential thermal analysis, x-ray diffraction, and ultraviolet–visible spectroscopy, while the microstructure of thin films was revealed by transmission electron microscopy. The results indicate that the Ag spherical particles with the diameter of 10–20 nm were formed by breaking Si–O–Ag bonds above 200 °C and dispersed in the SiO2 matrix. The optical absorption property of Ag/SiO2 nanofilm in the visible range is enhanced, and the band gap (Eg) is widened with raising annealing temperatures, which is promising for the potential applications in nonlinear optical and related fields.