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Ideological and Political Education is always the key course in China’s education system, which corresponding to in the west is generally called Civic Education. However, there are general stereotypes existing in both Ideological and Political Education in China and Civic Education in the west. This paper mainly studies the backgrounds of the courses of Ideological and Political Education in China by analyzing the standard of its revolution and innovation in detail. By comparing with Identity Education and Patriotism Education in the United States, Religious and Moral Education in the UK and Conflict Education in Germany, stress on Political Education in Western Civic Education and Moral Education in Ideological and Political Education in China. At last, this paper absorbed in the advantages of Civic Education offers some experience to the revolution of Ideological and Political Education in China.

This study aims to explore the application of big data technology in supply chain management, especially its role in coping with complex market demand and supply chain risks. Starting from both theoretical and practical case levels, the study systematically comprehends the key technologies of big data in supply chain management, including application scenarios such as demand forecasting, inventory management, production optimization, and supplier management. Through empirical analysis with Amazon as a case study, the study reveals how big data analytics can significantly improve the agility, efficiency, and risk resistance of the supply chain, which is manifested in the improvement of inventory turnover, reduction of supply chain cost, and optimization of logistics efficiency. A series of optimization strategies are proposed. The study systematically comprehends the core technologies of big data in supply chain management. This study analyzes their practical application effects in demand forecasting, inventory management, production optimization, logistics and distribution, and supplier management scenarios.

Parkinson’s disease (PD), one of the most common neurodegenerative disorders, is characterized by progressive neurodegeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). DJ-1 acts essential roles in neuronal protection and anti-neuroinflammatory response, and its loss of function is tightly associated with a familial recessive form of PD. However, the molecular mechanism of DJ-1 involved in neuroinflammation is largely unclear. Here, we found that wild-type DJ-1, rather than the pathogenic L166P mutant DJ-1, directly binds to the subunit p65 of nuclear factor-κB (NF-κB) in the cytoplasm, and loss of DJ-1 promotes p65 nuclear translocation by facilitating the dissociation between p65 and NF-κB inhibitor α (IκBα). DJ-1 knockout ( DJ-1 −/− ) mice exhibit more microglial activation compared with wild-type littermate controls, especially in response to lipopolysaccharide (LPS) treatment. In cellular models, knockdown of DJ-1 significantly upregulates the gene expression and increases the release of LPS-treated inflammatory cytokines in primary microglia and BV2 cells. Furthermore, DJ-1 deficiency in microglia significantly enhances the neuronal toxicity in response to LPS stimulus. In addition, pharmacological blockage of NF-κB nuclear translocation by SN-50 prevents microglial activation and alleviates the damage of DA neurons induced by microglial DJ-1 deficiency in vivo and in vitro. Thus, our data illustrate a novel mechanism by which DJ-1 facilitates the interaction between IκBα and p65 by binding to p65 in microglia, and thus repressing microglial activation and exhibiting the protection of DA neurons from neuroinflammation-mediated injury in PD.

•An MRI method was developed to assess BBB permeability in mice.•BBB permeability to water can be measured in 6 min without contrast agents.•BBB breakdown was observed in a mouse model of Huntington's disease. Blood-brain barrier (BBB) plays a critical role in protecting the brain from toxins and pathogens. However, in vivo tools to assess BBB permeability are scarce and often require the use of exogenous contrast agents. In this study, we aimed to develop a non-contrast arterial-spin-labeling (ASL) based MRI technique to estimate BBB permeability to water in mice. By determining the relative fraction of labeled water spins that were exchanged into the brain tissue as opposed to those that remained in the cerebral veins, we estimated indices of global BBB permeability to water including water extraction fraction (E) and permeability surface-area product (PS). First, using multiple post-labeling delay ASL experiments, we estimated the bolus arrival time (BAT) of the labeled spins to reach the great vein of Galen (VG) to be 691.2 ± 14.5 ms (N = 5). Next, we investigated the dependence of the VG ASL signal on labeling duration and identified an optimal imaging protocol with a labeling duration of 1200 ms and a PLD of 100 ms. Quantitative E and PS values in wild-type mice were found to be 59.9 ± 3.2% and 260.9 ± 18.9 ml/100 g/min, respectively. In contrast, mice with Huntington's disease (HD) revealed a significantly higher E (69.7 ± 2.4%, P = 0.026) and PS (318.1 ± 17.1 ml/100 g/min, P = 0.040), suggesting BBB breakdown in this mouse model. Reproducibility studies revealed a coefficient-of-variation (CoV) of 4.9 ± 1.7% and 6.1 ± 1.2% for E and PS, respectively. The proposed method may open new avenues for preclinical research on pathophysiological mechanisms of brain diseases and therapeutic trials in animal models.

•Overall BBB water permeability increased in AD mice, related to the attenuation of tight junction proteins.•Hippocampal TWE permeability was elevated in AD mice and associated with upregulated AQP4.•Impaired AQP4 PVS polarization was also found in AD mice.•Alterations of water exchange were correlated and can be predictive of aβ and tau deposition and might affect the waste clearance in the glymphatic neurofluid. Growing evidence suggests that Alzheimer's disease (AD) has been linked with the dysfunction of glymphatic system. Previous studies were primarily cross-sectional and focused on only one specific component, hindering the understanding of overall glymphatic function in AD. We evaluated the longitudinal changes in multiple components of glymphatic system (blood-brain barrier (BBB) and transcytolemmal water exchange (TWE) permeability) in AD mice. Five female wild-type and four 3 × Tg-AD mice from 5 to 13 months of age were scanned monthly using two non-contrast MRI techniques, water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) and diffusion-time-dependent kurtosis imaging (tDKI), yielding BBB and TWE permeability. Immunostaining was used to evaluate tight junction proteins associated with BBB structural integrity, aquaporin 4 (AQP4) related to TWE, and AQP4 perivascular space (PVS) polarization that might represent PVS-parenchyma water exchange. The relationship between glymphatic function and AD pathology, as measured by amyloid beta (Aβ) and tau deposition, was also explored. Our results revealed significantly increased BBB and hippocampal TWE permeability in AD mouse brains, consistent with the histological findings of reduced tight junction proteins and upregulated AQP4, which were correlated with each other and can be predictive of Aβ and tau deposition. Impaired AQP4 PVS polarization was also found in AD mice. In conclusion, water exchange in multiple components of glymphatic system altered in AD mice, and these in vivo MRI findings were validated pathologically, which might affect the waste clearance in the glymphatic neurofluid. [Display omitted]

An ideal implant needs to have the ability to coordinate the foreign body response and tissue regeneration. Here, Hydrogenated‐silicon nanosheets (H‐Si NSs) with favorable biodegradability are integrated and functionalized into a β‐tricalcium phosphate scaffold (H‐Si TCP) for bone defect healing. H‐Si TCP can greatly improve bone regeneration through osteoimmunomodulation‐guided biodegradation in vivo. The spatiotemporal regulation of degradation products replenishes sufficient nutrients step by step for the entire process of bone repair. Extracellular and intracellular reactive oxygen species (ROS) are first downregulated by reaction with H‐Si NSs, followed by marked M2 polarization, remodeling the micro‐environment timely for immune‐bone regeneration. The release of primary reaction products awakened bone marrow mesenchymal stem cells (BMSCs), which are converted into osteoblasts anchored on scaffolds. Subsequently, biomineralization is promoted by the final degradation products. The intrinsic ROS‐responsive, immunoregulatory, and osteo‐promotive capability of 2D H‐Si NSs makes such composite H‐Si TCP scaffold a highly potential alternative for the treatment of critical bone defect. A novel 2D hydrogenated‐silicon nanosheet (H‐Si NSs) is integrated and functionalized into a β‐tricalcium phosphate scaffold (H‐Si TCP) for immuno‐bone remodeling in our study. H‐Si NSs has great ROS‐responsive, immunoregulatory, and osteo‐promotive property and H‐Si TCP can provide sufficient ingredients and greatly improve bone regeneration step by step through osteoimmunomodulation‐guided biodegradation in vivo.

A GGGGCC hexanucleotide repeat expansion in intron 1 of chromosome 9 open reading frame 72 ( C9ORF72 ) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Repeat-associated non-ATG translation of dipeptide repeat proteins (DPRs) contributes to the neuropathological features of c9FTD/ALS. Among the five DPRs, arginine-rich poly-PR are reported to be the most toxic. Here, we generate a transgenic mouse line that expresses poly-PR (GFP-PR 28 ) specifically in neurons. GFP-PR 28 homozygous mice show decreased survival time, while the heterozygous mice show motor imbalance, decreased brain weight, loss of Purkinje cells and lower motor neurons, and inflammation in the cerebellum and spinal cord. Transcriptional analysis shows that in the cerebellum, GFP-PR 28 heterozygous mice show differential expression of genes related to synaptic transmission. Our findings show that GFP-PR 28 transgenic mice partly model neuropathological features of c9FTD/ALS, and show a role for poly-PR in neurodegeneration. Repeat-associated non-ATG translation of dipeptide repeat proteins (DPRs) contributes to disease manifestation in FTD/ALS associated with the hexanucleotide repeat expansion of the C9ORF72 gene. Here the authors show that a transgenic mouse line expressing poly-PR28 in neurons displays some signs of neuronal loss that mirrors that seen in the disease.

Brown-marbled grouper, Epinephelus fuscoguttatus, is not only an important commercial fish species, but also an important crossbreeding parent in grouper industry. Improvement of growth traits of this species contributes to the development of grouper breeding. Currently, the development of molecular marker associated with growth of brown-marbled grouper is rare. Thus, we performed the first genome-wide association study (GWAS) for five growth traits in 172 brown-marbled groupers with 43,688 SNPs detected by ddRAD-seq. We identified a total of 5 significant and 18 suggestive QTLs located in multiple chromosomes associated with growth traits. In the 20 kb window of the significant SNPs and suggestive SNPs, 5 and 14 potential candidate genes affecting growth were detected, respectively. Five potential candidate genes near the significantly associated SNPs were selected for expression analysis. Among of which, bmp2k, wasf1, and acyp2 involved in bone development, maintenance of mitochondrion structure, and metabolism were differentially expressed. Interestingly, the SNP 23:29601315 located in the intron of bmp2k was significantly associated with body weight, body length, body height, and body thickness and suggestively associated with total length. We verified the locus using another new group including 123 individuals. The results showed that individuals with CC genotype have better growth traits comparing other individuals. Our findings not only contribute to understanding the molecular mechanism of growth regulation, but also promote the advance of marker-assisted selection in brown-marbled grouper.

•A novel MRI technique was developed to provide a non-invasive assessment of oxygen extraction fraction in the medial temporal lobe (MTL-OEF) in less than 5 minutes.•MTL-OEF was measured to be 23.9±3.6% in healthy adults and was significantly lower (P<0.0001) than the OEF of 33.3±2.9% in superficial cortical tissues.•In caffeine ingestion challenges, MTL-OEF was elevated by 9.1±4.0%.•MTL-OEF increased with age (MTL-OEF=20.997+0.100 × age; P=0.02). The medial temporal lobe (MTL) is a key area implicated in many brain diseases, such as Alzheimer's disease. As a functional biomarker, the oxygen extraction fraction (OEF) of MTL may be more sensitive than structural atrophy of MTL, especially at the early stages of diseases. However, there is a lack of non-invasive techniques to measure MTL-OEF in humans. The goal of this work is to develop an MRI technique to assess MTL-OEF in a clinically practical time without using contrast agents. The proposed method measures venous oxygenation (Yv) in the basal veins of Rosenthal (BVs), which are the major draining veins of the MTL. MTL-OEF can then be estimated as the arterio-venous difference in oxygenation. We developed an MRI sequence, dubbed arterial-suppressed accelerated T2-relaxation-under-phase-contrast (AS-aTRUPC), to quantify the blood T2 of the BVs, which was then converted to Yv through a well-established calibration model. MTL-OEF was calculated as (Ya−Yv)/Ya × 100%, where Ya was the arterial oxygenation. The feasibility of AS-aTRUPC to quantify MTL-OEF was evaluated in 16 healthy adults. The sensitivity of AS-aTRUPC in detecting OEF changes was assessed by a caffeine ingestion (200 mg) challenge. For comparison, T2-relaxation-under-spin-tagging (TRUST) MRI, which is a widely used global OEF technique, was also acquired. The dependence of MTL-OEF on age was examined by including another seven healthy elderly subjects. The results showed that in healthy adults, MTL-OEF of the left and right hemispheres were correlated (P=0.005). MTL-OEF was measured to be 23.9±3.6% (mean±standard deviation) and was significantly lower (P<0.0001) than the OEF of 33.3±2.9% measured in superior sagittal sinus (SSS). After caffeine ingestion, there was an absolute percentage increase of 9.1±4.0% in MTL-OEF. Additionally, OEF in SSS measured with AS-aTRUPC showed a strong correlation with TRUST OEF (intra-class correlation coefficient=0.94 with 95% confidence interval [0.91, 0.96]), with no significant bias (P=0.12). MTL-OEF was found to increase with age (MTL-OEF=20.997+0.100 × age; P=0.02). In conclusion, AS-aTRUPC MRI provides non-invasive assessments of MTL-OEF and may facilitate future clinical applications of MTL-OEF as a disease biomarker.

Cerebrovascular reactivity (CVR), an index of brain vessel’s dilatory capacity, is typically measured using hypercapnic gas inhalation or breath-holding as a vasoactive challenge. However, these methods require considerable subject cooperation and could be challenging in clinical studies. More recently, there have been attempts to use resting-state BOLD data to map CVR by utilizing spontaneous changes in breathing pattern. However, in subjects who have small fluctuations in their spontaneous breathing pattern, the CVR results could be noisy and unreliable. In this study, we aim to develop a new method for CVR mapping that does not require gas-inhalation yet provides substantially higher sensitivity than resting-state CVR mapping. This new method is largely based on resting-state scan, but introduces intermittent modulation of breathing pattern in the subject to enhance fluctuations in their end-tidal CO2 (EtCO2) level. Here we examined the comfort level, sensitivity, and accuracy of this method in two studies. First, in 8 healthy young subjects, we developed the intermittent breath-modulation method using two different modulation frequencies, 6 ​s per breath and 12 ​s per breath, respectively, and compared the results to three existing CVR methods, specifically hypercapnic gas inhalation, breath-holding, and resting-state. Our results showed that the comfort level of the 6-s breath-modulation method was significantly higher than breath-holding (p ​= ​0.007) and CO2-inhalation (p ​= ​0.015) methods, while not different from the resting-state, i.e. free breathing method (p ​= ​0.52). When comparing the sensitivity of CVR methods, the breath-modulation methods revealed higher Z-statistics compared to the resting-state scan (p ​< ​0.008) and was comparable to breath-holding results. Next, we tested the feasibility of breath-modulation CVR mapping (6 ​s per breath) in 21 cognitively normal elderly participants and compared quantitative CVR values to that obtained with the CO2-inhalation method. Whole-brain CVR was found to be 0.150 ​± ​0.055 and 0.154 ​± ​0.032 %ΔBOLD/mmHg for the breath-modulation and CO2-inhalation method, respectively, with a significant correlation between them (y ​= ​0.97x, p ​= ​0.007). CVR mapping with intermittent breath modulation may be a useful method that combines the advantages of resting-state and CO2-inhalation based approaches. •A new method was proposed to map CVR without gas inhalation.•It is based on resting-state scan but introduces intermittent breath modulations.•This method is comfortable to the subjects and has good sensitivity in CVR mapping.•This method provides absolute CVR quantification and relative CVR maps reliably.•This method combines the advantages of resting-state and CO2-inhalation approaches.