Search

Abstract Background Previous research has examined the associations of preschoolers’ 24-h movement behaviours, including light and moderate-to-vigorous physical activity (LPA and MVPA), sedentary behaviour (SB), sleep, with physical fitness in isolation, ignoring intrinsically compositional nature of movement data while increasing the risk of collinearity. Thus, this study investigated the associations of preschoolers’ 24-h Movement behaviours composition with physical fitness, estimated changes in physical fitness when time was reallocated between movement behaviours composition, and determined whether associations differ between different genders, using compositional data analysis. Methods In the cross-sectional study, a total of 275 preschoolers (3 ~ 6 y) from China were included. SB, LPA and MVPA times were objectively monitored with an ActiGraph GT9X accelerometer for 7 consecutive days. Sleep duration was obtained using parental reports. Physical fitness parameters, including upper and lower limb strength, static balance, speed-agility, and cardiorespiratory fitness (CRF), were determined with the PREFIT battery. The associations of 24-h movement behaviours composition with each physical fitness parameter were examined employing compositional multivariable linear regression models. The changes following time reallocation among behaviours were estimated employing compositional isotemporal substitution analyses. Results Greater MVPA, but not LPA, was significantly related to better upper and lower limb strength, speed-agility, and CRF. Reallocating time from LPA or SB to MVPA was related to better physical fitness. The associations were non-symmetrical: the estimated detriments to physical fitness from replacing MVPA with LPA or SB were larger than the estimated benefits associated with adding MVPA of the same magnitude. The aforementioned associations with lower limb strength, CRF, and speed-agility were observed in boys, while associations with upper and lower limb strength were noted in girls. Conclusion Our findings reinforce the importance of physical activity (PA) intensity for the development of physical fitness in preschoolers. Replacing LPA or SB time with MVPA may be an appropriate strategy for enhancing preschoolers’ physical fitness.

Abstract Preharvest sprouting (PHS) is a serious problem in rice production as it leads to reductions in grain yield and quality. However, the underlying mechanism of PHS in rice remains unclear. In this study, we identified and characterized a preharvest sprouting and seedling lethal (phssl) mutant. The heterozygous phssl/+ mutant exhibited normal plant development, but severe PHS in paddy fields. However, the homozygous phssl mutant was seedling lethal. Gene cloning and genetic analysis revealed that a point mutation in OsABA3 was responsible for the mutant phenotypes. OsABA3 encodes a molybdenum cofactor (Moco) sulfurase. The activities of the sulfureted Moco-dependent enzymes such as aldehyde oxidase (AO) and xanthine dehydrogenase (XDH) were barely detectable in the phssl mutant. As the final step of abscisic acid (ABA) de novo biosynthesis is catalyzed by AO, it indicated that ABA biosynthesis was interrupted in the phssl mutant. Exogenous application of ABA almost recovered seed dormancy of the phssl mutant. The knock-out (ko) mutants of OsABA3 generated by CRISPR-Cas9 assay, were also seedling lethal, and the heterozygous mutants were similar to the phssl/+ mutant showing reduced seed dormancy and severe PHS in paddy fields. In contrast, the OsABA3 overexpressing (OE) plants displayed a significant increase in seed dormancy and enhanced plant resistance to PHS. The AO and XDH activities were abolished in the ko mutants, whereas they were increased in the OE plants. Notably, the Moco-dependent enzymes including nitrate reductase (NR) and sulfite oxidase (SO) showed reduced activities in the OE plants. Moreover, the OE plants exhibited enhanced resistances to osmotic stress and bacterial blight, and flowered earlier without any reduction in grain yield. Taken together, this study uncovered the crucial functions of OsABA3 in Moco sulfuration, plant development, and stress resistance, and suggested that OsABA3 is a promising target gene for rice breeding.

Offline programming (OLP) is a mainstream approach for controlling assembly robots at construction sites. However, existing methods are tailored to specific assembly tasks and workflows, and thus lack flexibility. Additionally, the emerging large language model (LLM)-based OLP cannot effectively handle the code logic of robot programming. Thus, this paper addresses the question: How can robot control programs be generated effectively and accurately for diverse construction assembly tasks using LLM techniques? This paper describes a closed user-on-the-loop control framework for construction assembly robots based on LLM techniques. A hierarchical strategy to generate robot control programs is proposed to logically integrate code generation at high and low levels. Additionally, customized application programming interfaces and a chain of action are combined to enhance the LLM's understanding of assembly action logic. An assembly task set was designed to evaluate the feasibility and reliability of the proposed approach. The results show that the proposed approach (1) is widely applicable to diverse assembly tasks, and (2) can improve the quality of the generated code by decreasing the number of errors. Our approach facilitates the automation of construction assembly tasks by simplifying the robot control process.

IntroductionThe tumor microenvironment and IRGs are highly correlated with tumor occurrence, progression, and prognosis. However, their roles in grade II and III gliomas, termed LGGs in this study, remain to be fully elucidated. Our research aims to develop immune-related features for risk stratification and prognosis prediction in LGG.MethodsUsing the ssGSEA method, we assessed the immune characteristics of the LGG population. We conducted differential analysis using LGG samples from the TCGA database and normal samples from GTEx, identifying 412 differentially expressed immune-related genes (DEIRGs). Subsequently, we utilized univariate Cox, LASSO, and multivariate Cox regression analyses to establish both a gene predictive model and a nomogram predictive model.ResultsHere, we found that the ESTIMATE score, immune score and stromal score of high-immunity, high-grade and isocitrate dehydrogenase (IDH) wild-type glioma were higher than those of the corresponding group, and the tumor purity was lower. Higher ESTIMATE scores, stromal scores and immune scores indicated a poor prognosis in patients with LGG. Our four-gene prognostic model demonstrated superior accuracy compared to other molecular features. Validation using the CGGA as a testing set and the combined TCGA and CGGA cohort confirmed its robust prognostic value. Additionally, a nomogram integrating the prognostic model and clinical variables showed enhanced predictive capability.DiscussionOur study highlights the prognostic significance of the identified four DEIRGs (KLRC3, MR1, PDIA2, and RFXAP) in LGG patients. The predictive model and nomogram developed herein offer valuable tools for personalized treatment strategies in LGG. Future research should focus on further validating these findings and exploring the functional roles of these DEIRGs within the LGG tumor microenvironment.

The guided tissue regeneration (GTR) procedure has become an important process for the treatment of periodontal tissue regeneration, using the membrane as a mechanical barrier to generate a distance across the defect that subsequently allowing bone regeneration. Due to the complexity of periodontal microenvironment caused by bacterial infections, inflammation, and fibrous tissue penetration, the guided tissue regeneration membrane is required to have antibacterial and barrier functions. We developed a loaded methylene blue @ ZIF-8 and hydroxyapatite gradient thermoplastic polyurethane Janus membrane for antibacterial osteogenic and barrier. This Janus membrane with a porous gradient structure was prepared to use phase-conversion method. The rough layer facilitated cell growth and promoted periodontal bone regeneration, whereas the smooth layer isolated the growing fiber tissue.The rapid release of reactive oxygen species in the early stage and continuous release of zinc ions by methylene blue @ZIF-8 can achieve long-term synergistic antibacterial effect, with antibacterial rates of 84 % and 72 % against Escherichia coli and Staphylococcus aureus, respectively, which can effectively reduce the local inflammation caused by bacteria. In summary, we applied the Janus membrane to a rat periodontal bone defect model, and the membrane showed good surgical performance, barrier properties, osteogenic properties, and antibacterial effects, which could have broad application prospects in the treatment of periodontal bone defects.

Abstract Background Hybrid rice has significant yield advantage and stress tolerance compared with inbred rice. However, production of hybrid rice seeds requires extensive manual labors. Currently, hybrid rice seeds are produced by crosspollination of male sterile lines by fertile paternal lines. Because seeds from paternal lines can contaminate the hybrid seeds, mechanized production by mixed-seeding and mixed-harvesting is difficult. This problem can be solved if the paternal line is female sterile. Results Here we identified a female infertile mutant named h569 carrying a novel mutation (A1106G) in the MEL2 gene that was previously reported to regulate meiosis entry both in male and female organs. h569 mutant is female infertile but male normal, suggesting that MEL2 regulates meiosis entry in male and female organs through distinct pathways. The MEL2 gene and h569 mutant gave us tools to construct female sterility maintaining systems that can be used for propagation of female sterile lines. We connected the wild-type MEL2 gene with pollen-killer gene ZmAA1 and seed-marker gene DsRed2 in one T-DNA cassette and transformed it into ZZH1607, a widely used restorer line. Transgenic line carrying a single transgene inserted in an intergenic region was selected to cross with h569 mutant. F2 progeny carrying homozygous A1106G mutation and hemizygous transgene displayed 1:1 segregation of fertile and infertile pollen grains and 1:1 segregation of fluorescent and non-fluorescent seeds upon self-fertilization. All of the non-fluorescent seeds generated female infertile plants, while the fluorescent seeds generated fertile plants that reproduced in the way as their previous generation. Conclusions These results indicated that the female sterility maintaining system constructed in the study can be used to breed and propagate paternal lines that are female infertile. The application of this system will enable mechanized production of hybrid rice seed by using the mixed-seeding and mixed harvesting approach, which will significantly reduce the cost in hybrid rice seed production.

This is an essay in the field of ceramics and composites.To achieve carbon neutrality and peaking carbon dioxide emissions, the low-iron quartz sand(\begin{document}${{ \omega }}_{{\text{Fe}}_{\text{2}}{\text{O}}_{\text{3}}}$\end{document}≤0.010%) supply for photovoltaic glass is tightening in China, so the preparation of low-iron quartz sand from quartz associated with kaolin gradually attracting widespread attention. However, quartz associated with kaolin can usually be enriched in the tailings of kaolin physical beneficiation. Taking quartz associated kaolin which is from tailings of kaolin physical beneficiation in Hepu, Guangxi as the object,the effect of purification by size fraction distribution on the preparation of low iron quartz sand from quartz-associated kaolin was studied in this essay. The experimental results showed that the index of SiO2, Al2O3 and Fe2O3 content in size of 2 mm or more was better than that of 0.71~2 mm and 0.125~0.71 mm respectively, but for all different size fraction products, ferric oxide content of quartz sand is not less than 0.016% by grinding, hydraulic classification, magnetic separation and flotation. The content of quartz sand obtained by sulfuric acid and oxalic acid was 0.0091%, and the content of quartz sand obtained by hydrofluoric acid and oxalic acid was 0.0054% respectively, both of which meets the ferric oxide content requirement of low iron quartz sand for solar photovoltaic glass and optical glass.

Abstract Rice (Oryza sativa L.) is one of the most important food crops worldwide. The utilisation of heterosis (hybrid vigour) has played a significant role in increasing rice yield and ensuring food supply. Over the past 50 years, the first-generation three-line system based on cytoplasmic male sterility, and the second-generation two-line system based on environment-sensitive genic male sterility (EGMS), have been widely applied in hybrid rice production. However, the three-line system is restricted by the matching relationship among the three parental lines and allows only ~ 2–5% of germplasms to be explored for elite combinations. The environmental sensitivity of EGMS lines has posed serious risks to the production of hybrid seeds. These factors have hindered the development and applications of hybrid rice. Third-generation hybrid rice technology (TGHRT) is based on environment-insensitive genic male sterility, which can effectively overcome the intrinsic problems of the three-line and two-line systems. Since the establishment of TGHRT, numerous findings and innovations have been reported. This paper gives a brief review of traditional hybrid rice technologies and discusses the establishment of TGHRT, technical innovations in TGHRT, and future research that is necessary to promote the wide application of TGHRT in rice production.

Abstract Background The prevalence of childhood obesity and overweight has risen globally, leading to increased rates of metabolic disorders. Various factors, including genetic, epigenetic, and environmental influences such as diet and physical activity, contribute to pediatric obesity. This study aimed to identify specific circulating miRNAs as potential biomarkers for assessing obesity in children. Methods Thirty children, including 15 obese and 15 extremely thin individuals, were selected for this study. MiRNA expression in circulating plasma was assessed using miRNA microarrays. The reliability of differential miRNA expression was confirmed using TaqMan qPCR. The correlation between miRNAs and obesity was analyzed through multiple linear regression, receiver operator characteristic (ROC) curve analysis, and odds ratio (OR) calculations. Bioinformatics tools were utilized to identify target genes for the selected miRNAs, and a functional network map was constructed. Results A total of 36 differentially expressed miRNAs were identified through gene chip analysis, and TaqMan qPCR validation confirmed the upregulation of seven miRNAs: hsa-miR-126-3p, hsa-miR-15b-5p, hsa-miR-199a-3p, hsa-miR-20a-5p, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-24-3p. Among these, hsa-miR-15b-5p and hsa-miR-223-3p exhibited a statistically significant difference except for hsa-miR-23a-3p. These two miRNAs showed more predicted target genes related to obesity than others. Multiple linear regression analysis revealed an association between obesity and hsa-miR-15b-5p and hsa-miR-223-3p [10.529 (4.974–16.084), -10.225 (-17.852~ -2.657)]. Even after adjusting for age and sex, these two miRNAs remained associated with obesity [8.936 (3.572–14.301), -8.449(-15.634~ -1.303)]. The area under the ROC curve (AUC) reached values of 0.816, 0.711, and 0.929, respectively. Odds ratio analysis demonstrated a significant correlation between obesity and hsa-miR-15b-5p (OR = 143, 95% CI 5.80 to 56,313, p = 0.024) and between obesity and hsa-miR-223-3p (OR = 0.01, 95% CI 0.00 to 0.23, p = 0.037). Importantly, hsa-miR-15b-5p was found to have numerous target genes associated with the FoxO, insulin, Ras, and AMPK signaling pathways. Conclusions Differential miRNA expression profiles in the circulation of obese children compared to controls suggest underlying metabolic abnormalities. Hsa-miR-15b-5p and hsa-miR-223-3p may be considered as molecular markers for the screening of obese children and populations at risk of developing metabolic syndrome.

Abstract Background The P-stalk is a conserved and vital structural element of ribosome. The eukaryotic P-stalk exists as a P0-(P1-P2)2 pentameric complex, in which P0 function as a base structure for incorporating the stalk onto 60S pre-ribosome. Prior studies have suggested that P0 genes are indispensable for survival in yeast and animals. However, the functions of P0 genes in plants remain elusive. Results In the present study, we show that rice has three P0 genes predicted to encode highly conserved proteins OsP0A, OsP0B and OsP0C. All of these P0 proteins were localized both in cytoplasm and nucleus, and all interacted with OsP1. Intriguingly, the transcripts of OsP0A presented more than 90% of the total P0 transcripts. Moreover, knockout of OsP0A led to embryo lethality, while single or double knockout of OsP0B and OsP0C did not show any visible defects in rice. The genomic DNA of OsP0A could well complement the lethal phenotypes of osp0a mutant. Finally, sequence and syntenic analyses revealed that OsP0C evolved from OsP0A, and that duplication of genomic fragment harboring OsP0C further gave birth to OsP0B, and both of these duplication events might happen prior to the differentiation of indica and japonica subspecies in rice ancestor. Conclusion These data suggested that OsP0A functions as the predominant P0 gene, playing an essential role in embryo development in rice. Our findings highlighted the importance of P0 genes in plant development.

The clinical treatments of bone defects remain a challenge. Hydrogels containing bone marrow mesenchymal stem cells (BMSCs) are extensively used to bone regeneration because of excellent biocompatibility and hydrophilicity. However, the insufficient osteo-induction capacity of the BMSC-loaded hydrogels limits their clinical applications. In this study, bio-active glass (BG) and BMSCs were combined with gelatin methacryloyl (GelMA) to fabricate composite hydrogels via photo-crosslinking, and the regulation of bone regeneration was investigated. In vitro experiments showed that the BG/BMSCs@GelMA hydrogel had excellent cytocompatibility and promoted osteogenic differentiation in BMSCs. Furthermore, the BG/BMSCs@GelMA hydrogel was injected into critical-sized calvarial defects, and the results further confirmed its excellent angiogenetic and bone regeneration capacity. In addition, BG/BMSCs@GelMA promoted the polarization of macrophages towards the M2 phenotype. In summary, this novel composite hydrogel demonstrated remarkable potential for application in bone regeneration due to its immunomodulatory, excellent angiogenetic as well as osteo-induction capacity.

Abstract Objective Hypoxia can promote stem cell proliferation and migration through HIF-1α. Hypoxia can regulate cellular endoplasmic reticulum (ER) stress. Some studies have reported the relationship among hypoxia, HIF-α, and ER stress, however, while little is known about HIF-α and ER stress in ADSCs under hypoxic conditions. The purpose of the study was to investigate the role and relationship of hypoxic conditions, HIF-1α and ER stress in regulating adipose mesenchymal stem cells (ADSCs) proliferation, migration, and NPC-like differentiation. Method ADSCs were pretreated with hypoxia, HIF-1α gene transfection, and HIF-1α gene silence. The ADSCs proliferation, migration, and NPC-like differentiation were assessed. The expression of HIF-1α in ADSCs was regulated; then, the changes of ER stress level in ADSCs were observed to investigate the relationship between ER stress and HIF-1α in ADSCs under hypoxic conditions. Result The cell proliferation and migration assay results show that hypoxia and HIF-1α overexpression can significantly increase the ADSCs proliferation and migration, while HIF-1α inhibition can significantly decrease the ADSCs proliferation and migration. The HIF-1α and co-cultured with NPCs played an important role in the directional differentiation of ADSCs into NPCs. The hypoxia-regulated ER stress in ADSCs through the HIF-1α pathway, thereby regulating the cellular state of ADSCs, was also observed. Conclusion Hypoxia and HIF-1α play important roles in proliferation, migration, and NPC-like differentiation of ADSCs. This study provides preliminary evidence that HIF-1α-regulated ER stress thus affects ADSCs proliferation, migration, and differentiation. Therefore, HIF-1α and ER may serve as key points to improve the efficacy of ADSCs in treating disc degeneration.

Abstract Rotating antenna radar is widely used on the airborne platform to extend the range of the radar detection airspace. However, the echo signal received by an airborne rotating radar is spread in the Doppler domain due to the platform motion and the antenna rotation. In the process of a long‐time integration, the antenna rotation harms the signal‐to‐noise ratio and reduces the performance of target detection when using conventional processing methods. Although conventional space‐time adaptive processing (STAP) has been used successfully to suppress clutter on an airborne radar, it does not take into account the antenna rotation. It decreases the performance of clutter suppression on the airborne rotating antenna radar. The signal model of airborne rotating antenna radar is analysed and the STAP technique to the rotating antenna scenario is improved to effectively suppress clutter and focus on target energy. Firstly, the echo of the airborne rotating antenna radar is modelled. Secondly, the factors affecting the Doppler difference of the array elements are investigated. Thirdly, an improved STAP method is proposed. Finally, the effect of antenna rotation on clutter Doppler characteristics and the clutter suppression and target energy focussing on the effects of the improved STAP technique are investigated. Experimental results demonstrate the effectiveness of the proposed method.

Obesity has become a serious global public health problem; a deeper understanding of systemic change of chromatin accessibility during human adipogenesis contributes to conquering obesity and its related diseases. Here, we applied the ATAC-seq method to depict a high-quality genome‐wide time-resolved accessible chromatin atlas during adipogenesis of human adipose-derived stem cells (hASCs). Our data indicated that the chromatin accessibility drastic dynamically reformed during the adipogenesis of hASCs and 8 h may be the critical transition node of adipogenesis chromatin states from commitment phase to determination phase. Moreover, upon adipogenesis, we also found that the chromatin accessibility of regions related to anti-apoptotic, angiogenic and immunoregulatory gradually increased, which is beneficial to maintaining the health of adipose tissue (AT). Finally, the chromatin accessibility changed significantly in intronic regions of peroxisome proliferator‐activated receptor γ during adipogenesis, and these regions were rich in transcription factors binding motifs that were exposed for further regulation. Overall, we systematically analysed the complex change of chromatin accessibility occurring in the early stage of adipogenesis and deepened our understanding of human adipogenesis. Furthermore, we also provided a good reference data resource of genome‐wide chromatin accessibility for future studies on human adipogenesis.

Periodontitis is a chronic inflammatory disease characterized by the colonization of pathogenic microorganisms and the loss of periodontal supporting tissue. However, the existing local drug delivery system for periodontitis has some problems including subpar antibacterial impact, easy loss, and unsatisfactory periodontal regeneration. In this study, a multi-functional and sustained release drug delivery system (MB/BG@LG) was developed by encapsulating methylene blue (MB) and bioactive glass (BG) into the lipid gel (LG) precursor by Macrosol technology. The properties of MB/BG@LG were characterized using a scanning electron microscope, a dynamic shear rotation rheometer, and a release curve. The results showed that MB/BG@LG could not only sustained release for 16 days, but also quickly fill the irregular bone defect caused by periodontitis through in situ hydration. Under 660 ​nm light irradiation, methylene blue-produced reactive oxygen species (ROS) can reduce local inflammatory response by inhibiting bacterial growth. In addition, in vitro and vivo experiments have shown that MB/BG@LG can effectively promote periodontal tissue regeneration by reducing inflammatory response, promoting cell proliferation and osteogenic differentiation. In summary, MB/BG@LG exhibited excellent adhesion properties, self-assembly properties, and superior drug release control capabilities, which improved the clinical feasibility of its application in complex oral environments.

Background: The effect of exercise on human metabolism is obvious. However, the effect of chronic exercise on liver metabolism in mice is less well described.Methods: The healthy adult mice running for 6 weeks as exercise model and sedentary mice as control were used to perform transcriptomic, proteomic, acetyl-proteomics, and metabolomics analysis. In addition, correlation analysis between transcriptome and proteome, and proteome and metabolome was conducted as well.Results: In total, 88 mRNAs and 25 proteins were differentially regulated by chronic exercise. In particular, two proteins (Cyp4a10 and Cyp4a14) showed consistent trends (upregulated) at transcription and protein levels. KEGG enrichment analysis indicated that Cyp4a10 and Cyp4a14 are mainly involved in fatty acid degradation, retinol metabolism, arachidonic acid metabolism and PPAR signaling pathway. For acetyl-proteomics analysis, 185 differentially acetylated proteins and 207 differentially acetylated sites were identified. Then, 693 metabolites in positive mode and 537 metabolites in negative mode were identified, which were involved in metabolic pathways such as fatty acid metabolism, citrate cycle and glycolysis/gluconeogenesis.Conclusion: Based on the results of transcriptomic, proteomics, acetyl-proteomics and metabolomics analysis, chronic moderate intensity exercise has certain effects on liver metabolism and protein synthesis in mice. Chronic moderate intensity exercise may participate in liver energy metabolism by influencing the expression of Cyp4a14, Cyp4a10, arachidonic acid and acetyl coenzyme A and regulating fatty acid degradation, arachidonic acid metabolism, fatty acyl metabolism and subsequent acetylation.

The metric learning method has been successfully developed in few-shot learning by learning the deeply embedded metric space. However, many methods ignore the relationship between the support set and the query set. In this paper, we propose the category relevance redirection network (CRRNet), which is a novel metric learning-based few-shot learning classification network. The learning of CRRNet includes two stages. In the category relevance pre-training stage, the convolutional block attention module (CBAM) and the classifier are jointly trained using the center loss and cross entropy loss. In the category redirection training stage, the meta fusion block and the weight generator are used to represent the weighted query set features, which are then input into the spatial attention generator to obtain the discriminative features for classification. CRRNet can not only learn the relevant category characteristics of the support set samples, but emphasizes the relevant category characteristics of the current task’s query samples. Experiments on three datasets show that CRRNet can greatly improve the embedding learning performance and classification accuracy of metric-based few-shot classification. For the 5-way 1-shot and 5-way 5-shot scenarios, CRRNet may produce 9.68 percent and 12.42 percent increases over the traditional methods on the miniImageNet dataset, respectively.

Although bone mesenchymal stem cell (BMSC) transplantation has been applied to the treatment of spinal cord injury (SCI), the effect is unsatisfactory due to the specific microenvironment (inflammation and oxidative stress) in the SCI area, which leads to the low survival rate of transplanted cells. Thus, additional strategies are required to improve the efficacy of transplanted cells in the treatment of SCI. Hydrogen possesses antioxidant and anti-inflammatory properties. However, whether hydrogen can enhance the effect of BMSC transplantation in the treatment of SCI has not yet been reported. This study was aimed at investigating whether hydrogen promotes the therapeutic effect of BMSC transplantation in the treatment of SCI in rats. In vitro, BMSCs were cultured in a normal medium and a hydrogen-rich medium to study the effect of hydrogen on the proliferation and migration of BMSCs. BMSCs were treated with a serum-deprived medium (SDM), and the effects of hydrogen on the apoptosis of BMSCs were studied. In vivo, BMSCs were injected into the rat model of SCI. Hydrogen-rich saline (5 ml/kg) and saline (5 ml/kg) were given once a day via intraperitoneal injection. Neurological function was evaluated using the Basso, Beattie, and Bresnahan (BBB) and CatWalk gait analyses. Histopathological analysis, oxidative stress, inflammatory factors (TNF-α, IL-1β, and IL-6), and transplanted cell viability were detected at 3 and 28 days after SCI. Hydrogen can significantly enhance BMSC proliferation and migration and tolerance to SDM. Hydrogen and BMSC codelivery can significantly enhance neurological function recovery by improving the transplant cell survival rate and migration. Hydrogen can enhance the migration and proliferation capacity of BMSCs to repair SCI by reducing the inflammatory response and oxidative stress in the injured area. Hydrogen and BMSC codelivery is an effective method to improve BMSC transplantation in the treatment of SCI.

Physical exercise benefits hippocampal function through various molecular mechanisms. Protein acetylation, a conserved and widespread post-translational modification, is involved in the synaptic plasticity and memory. However, whether exercise can change global acetylation and the role of acetylated proteins in the hippocampus have remained largely unknown. Herein, using healthy adult mice running for 6 weeks as exercise model and sedentary mice as control, we analyzed the hippocampal lysine acetylome and proteome by Liquid chromatography-tandem mass spectrometry. As a result, we profiled the lysine acetylation landscape for the hippocampus and identified 3,876 acetyl sites and 1,764 acetylated proteins. A total of 272 acetyl sites on 252 proteins were differentially regulated by chronic exercise, among which 18.58% acetylated proteins were annotated in mitochondria. These proteins were dominantly deacetylated and mainly associated with carbon-related metabolism, the Hippo signaling pathway, ribosomes, and protein processing. Meanwhile, 21 proteins were significantly expressed and enriched in the pathway of complement and coagulation cascades. Our findings provide a new avenue for understanding the molecular mechanisms underlying the benefits of exercise for hippocampal function and can contribute to the promotion of public health.

Plastid ribosomal proteins (PRPs) are necessary components for plastid ribosome biogenesis, playing essential roles in plastid development. The ribosomal protein L18 involved in the assemble of 5S rRNA and 23S rRNA, is vital for E. coli viability, but the functions of its homologs in plant plastid remain elusive. Here, we characterized the functions of the plant plastid ribosomal protein L18s (PRPL18s) in Arabidopsis and rice. AtPRPL18 was ubiquitously expressed in most of the plant tissues, but with higher expression levels in seedling shoots, leaves, and flowers. AtPRPL18 was localized in chloroplast. Genetic and cytological analyses revealed that a loss of function of AtPRPL18 resulted in embryo development arrest at globular stage. However, overexpression of AtPRPL18 did not show any visible phenotypical changes in Arabidopsis. The rice OsPRPL18 was localized in chloroplast. In contrast to AtPRPL18, knockout of OsPRPL18 did not affect embryo development, but led to an albino lethal phenotype at the seedling stage. Cytological analyses showed that chloroplast development was impaired in the osprpl18-1 mutant. Moreover, a loss-function of OsPRPL18 led to defects in plastid ribosome biogenesis and a serious reduction in the efficiency of plastid intron splicing. In all, these results suggested that PRPL18s play critical roles in plastid ribosome biogenesis, plastid intron splicing, and chloroplast development, and are essential for plant survival.

Heart failure with preserved ejection fraction (HFpEF) shows complicated and not clearly defined etiology and pathogenesis. Although no pharmacotherapeutics have improved the survival rate in HFpEF, exercise training has become an efficient intervention to improve functional outcomes. Here, we investigated N6-methyladenosine (m6A) RNA methylation modification in a “two-hit” mouse model with HFpEF and HFpEF with exercise (HFpEF + EXT). The manner of m6A in HFpEF and HFpEF + EXT hearts was explored via m6A-specific methylated RNA immunoprecipitation followed by high-throughput and RNA sequencing methods. A total amount of 3992 novel m6A peaks were spotted in HFpEF + EXT, and 426 differently methylated sites, including 371 hypermethylated and 55 hypomethylated m6A sites, were singled out for further analysis (fold change >2, p < 0.05). According to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, unique m6A-modified transcripts in HFpEF + EXT were associated with apoptosis-related pathway and myocardial energy metabolism. HFpEF + EXT had higher total m6A levels and downregulated fat mass and obesity-related (FTO) protein levels. Overexpression of FTO cancels out the benefits of exercise in HFpEF + EXT mice by promoting myocyte apoptosis, myocardial fibrosis and myocyte hypertrophy. Totally, m6A is a significant alternation of epitranscriptomic processes, which is also a potentially meaningful therapeutic target.

Airborne radar plays a crucial role in detecting aerial targets, but its detection capability can be significantly affected by strong ground clutter when operating in down-looking mode. The range-Doppler (RD) results of ground clutter in airborne radar may overlap the range-Doppler results of the targets, causing target occlusion and rendering them undetectable. In addition to target detection, accurate extraction of target parameters is also of great importance. Due to the high-speed movement of the airborne platform, targets may exhibit range-Doppler ambiguity, necessitating the use of appropriate methods to resolve the range-Doppler ambiguity. Aiming at the problem of target occlusion by clutter with range-Doppler two-dimensional ambiguity during airborne radar down-looking target detection, this paper conducts a study on the detection of airborne radar down-looking targets based on orthogonal signals combined with pulse repetition frequency (PRF) staggered transmission. An optimization method is employed to design multiple sets of PRF values, aiming to reduce the radar blind zone. The range-Doppler two-dimensional ambiguity of targets is resolved using multiple sets of PRF, and coherent processing is performed on the corresponding echoes using the transmission intervals, maximizing the utilization of radar transmission energy. This approach enhances the signal-to-noise ratio (SNR) and improves the detection performance and parameter estimation accuracy, particularly for low SNR targets. The superiority of the proposed approach is demonstrated through simulation experiments.

Abstract Background The third-generation hybrid rice technology can be constructed by transforming a recessive nuclear male sterile (NMS) mutant with a transgenic cassette containing three functional modules: the wild type male fertility gene to restore the fertility of the mutant, the pollen killer gene that specifically kills the pollen grains carrying the transgene, and the red fluorescence protein (RFP) gene to mark the transgenic seed (maintainer). The transgenic plant produces 1:1 NMS seeds and maintainer seeds that can be distinguished by the RFP signal. However, the RFP signals in the partially filled or pathogen-infected maintainer seeds are often too weak to be detected by RFP-based seed sorting machine, resulting in intermingling of the maintainer seeds with NMS seeds. Results Here we constructed a weight-based seed sorting system for the third-generation hybrid rice technology by silencing the genes encoding ADP-glucose pyrophosphorylase (AGP) essential for endosperm starch biosynthesis via endosperm-specific expression of artificial microRNAs (amiRNAs). In this system, the NMS seeds have normal endosperm and are heavy, but the maintainer seeds have shrunken endosperms and are light-weighted. The maintainer seeds can be easily and accurately sorted out from the NMS seeds by weight-sorting machines, so pure and fully filled NMS seeds are available. Conclusions The weight-based seed sorting system shows obvious advantages over the RFP-based seed sorting system in accuracy, efficiency, and cost for propagation of pure male sterile seeds. These characteristics will significantly increase the value and transgenic safety of the third-generation hybrid rice technology.

Summary: A delicate balance of BMP activity is critical for tissue formation and organogenesis. However, the mechanical molecular details in ensuring the proper duration and intensity of BMP signaling have yet to be fully elucidated. Here, we identified a zebrafish mutant with a disrupted gene encoding for the BTB/POZ and zinc finger protein myoneurin (Mynn). mynn−/− mutants exhibited severe loss of pharyngeal cartilage elements, owing to poor proliferation, blocked differentiation, and low viability of cranial neural crest cells. Depletion of mynn in both zebrafish embryos and mammalian cells led to a reduction of the BMP signal activity. Mechanistically, Mynn interacts with Smad proteins in the nucleus, thereby disrupting the association between Smad protein and the phosphatase Ppm1a. Ultimately, this interaction prevents Smad dephosphorylation. More broadly, our findings may provide a new strategy to balance BMP signal activity via competitive binding of Mynn and Ppm1a to Smad proteins during pharyngeal cartilage formation.

Abstract Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/β-catenin pathway causes defective anteroposterior patterning, which results in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We have identified that folate deficiency activated Wnt/β-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promoted formation of the Gcm1/β-catenin/T-cell factor (TCF4) complex formation to regulate the Wnt targeted gene transactivation through Wnt-responsive elements. Moreover, the transcription factor Nanog upregulated Gcm1 transcription in mESCs under folate deficiency. Lastly, in NTDs mouse models and low-folate NTDs human brain samples, Gcm1 and Wnt/β-catenin targeted genes related to neural tube closure are specifically overexpressed. These results indicated that low-folate level promoted Wnt/β-catenin signaling via activating Gcm1, and thus leaded into aberrant vertebrate neural development.

With the increasing installed capacity of wind turbines, ensuring the safe operation of wind turbines is of great significance. However, the failure of wind turbines is still a severe problem, especially as blade damage can cause serious harm. To detect blade damage in time and prevent the accumulation of microdamage of blades evolving into severe injury, a damage dataset based on GH Bladed simulation of blade damage is proposed. Then, based on the wavelet packet analysis theory method, the MATLAB software can automatically analyze and extract the energy characteristics of the signal to identify the damage. Finally, the GH Bladed simulation software and MATLAB software are combined for fault diagnosis analysis. The results show that the proposed method based on GH Bladed to simulate blade damage and wavelet packet analysis can extract damage characteristics and identify single-unit damage, multiple-unit damage, and different degrees of damage. This method can quickly and effectively judge the damage to wind turbine blades; it provides a basis for further research on wind turbine blade damage fault diagnosis.

Distributed coherent aperture radar (DCAR) can realize high-precision long-range detection because of its excellent angular resolution. However, it is accompanied by a low search efficiency problem caused by the narrow main lobe and the angular ambiguity problem stemming from the high grating lobes. By simultaneously utilizing multiple grating lobes, we propose an effective search method and pertinent unambiguous signal processing algorithms to address the issue of using collocated DCAR for unambiguous target search. We investigate the beam migration of a grating lobe-irradiated target at various frequencies in order to carry out the multi-frequency coherent integration of the suggested search method in DCAR. In order to address the issue of using multiple beam lobes to simultaneously detect multiple targets, we also take into account the scenario of multiple targets and introduce the multiple hypothesis method to solve the problem. The DCAR search efficiency can be improved by tens of times through grating lobes exploitation, which makes use of DCAR to make the searches feasible. We also improved the performance of multi-frequency DOA ambiguity solving compared to existing algorithms with the sliding window clustering scheme. The viability of using grating lobes for the DCAR target searching and detection is shown in simulations. The experiments confirm the performance enhancement of multi-frequency coherent integration for parameter estimation.

Abstract Background Our previous study had shown that microRNA (miR)-302a played a key role in folate deficiency-induced apoptosis in mouse embryonic stem cells. However, details regarding the mechanism remain unclear. Transcription factors (TFs) and miRNAs are two key elements in gene regulation. The aim of this study is to construct the TF-miRNA gene regulation network and demonstrate its possible mechanism. Methods The TF-miRNA gene regulation network was constructed via bioinformatics methods. Chromatin immuno-coprecipitation PCR was selected to confirm the binding between miR-302a and TF. mRNA and protein levels were detected by Real-time quantitative PCR and western blotting. TargetScan prediction and Dual-Luciferase Reporter Assay system were used to confirm whether the miRNA binded directly to the predicted target gene. Results FOXO1 and miR-302a were selected as the key TF and miRNA, respectively. FOXO1 was confirmed to bind directly to the upstream promoter region of miR-302a. Real-time quantitative PCR and immunoblotting showed that in folate-free conditions, miR-302a and AKT were down regulated, while FOXO1 and Bim were up-regulated significantly. Additionally, treatment with LY294002 inhibitor revealed the involvement of the Akt/FOXO1/Bim signaling pathway in folate deficiency-induced apoptosis, rather than the ERK pathway. Finally, TargetScan prediction and double luciferase reporting experiments illustrated the ability of miR-302a to target the Bim 3′UTR region. Conclusion The involvement of miR-302a in folate deficiency-induced apoptosis through the AKT-FOXO1-BIM pathway in mESCs is a unique demonstration of the regulation mechanism of nutrient expression in embryonic development.

Abstract Background World Health Organisation (WHO) Guidelines on Physical Activity, Sedentary Behaviour and Sleep for Children under 5 Years of Age were released in 2019. The aim of this study was to examine the proportion of Chinese kindergarten children who met each individual guideline and each combination of the guidelines and the associations with adiposity. Methods Participants were 254 kindergarten children aged 4.1–6.3 years recruited from three kindergartens in urban area of Beijing. Physical activity, sedentary behaviour and sleep duration were assessed using 24-h accelerometry over three consecutive days. Screen time was reported by parents. Weight and height were measured; and children were categorised into normal weight and overweight/obese groups according to the WHO age- and sex- specific criteria. Frequency analyses were performed to examine the proportion of children meeting individual and combination of these guidelines. Logistics regression analyses were conducted to examine the associations between guideline compliance and adiposity. Results The proportion of children who met the physical activity (≥ 3 h daily physical activity, including ≥1 h daily moderate- to vigorous-intensity physical activity (MVPA)), sedentary screen time (

Background Transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), and microwave ablation (MWA) are regarded as effective therapies for treating unresectable hepatocellular carcinoma (HCC). We conducted this study to compare the efficiency and safety of TACE combined with RFA (TR group) or MWA (TM group). Method PubMed, the Cochrane Library, Ovid Medline, Web of Science, Scopus, Embase, ScienceDirect, and Google Scholar were searched. The primary endpoints were overall survival (OS), progression-free survival (PFS), response rates, and complications. Result Eight cohort studies and one randomized controlled trial were included. The TM group had better OS (Hazard ratio [HR]: 1.55; 95% confidence interval [CI]: 1.09–2.21, p = 0.01) and a better 2- and 3-year OS rate, 24-month PFS rate (Risk ratio [RR]: 0.67; 95% CI: 0.46–0.96, p = 0.03), and complete response rate (RR: 0.87; 95% CI: 0.79–0.96, p = 0.003) than the TR group. Furthermore, the TM and TR groups did not show significant differences in PFS, the disease control rate or complications. The advantage of TM was mainly reflected in younger patients (50–60 years old) compared with patients aged 60–70 years, as well as in patients with larger tumors (≥3 cm) compared with patients with tumors

Abstract Background Neural tube defects (NTDs) are severe, common birth defects that result from failure of normal neural tube closure during early embryogenesis. Accumulating strong evidence indicates that genetic factors contribute to NTDs etiology, among them, HOX genes play a key role in neural tube closure. Although abnormal HOX gene expression can lead to NTDs, the underlying pathological mechanisms have not fully been understood. Method We detected that H3K27me3 and expression of the Hox genes in a retinoic acid (RA) induced mouse NTDs model on E8.5, E9.5 and E10.5 using RNA-sequencing and chromatin immunoprecipitation sequencing assays. Furthermore, we quantified 10 Hox genes using NanoString nCounter in brain tissue of fetuses with 39 NTDs patients including anencephaly, spina bifida, hydrocephaly and encephalocele. Results Here, our results showed differential expression in 26 genes with a > 20-fold change in the level of expression, including 10 upregulated Hox genes. RT-qPCR revealed that these 10 Hox genes were all upregulated in RA-induced mouse NTDs as well as RA-treated embryonic stem cells (ESCs). Using ChIP-seq assays, we demonstrate that a decrease in H3K27me3 level upregulates the expression of Hox cluster A–D in RA-induced mouse NTDs model on E10.5. Interestingly, RA treatment led to attenuation of H3K27me3 due to cooperate between UTX and Suz12, affecting Hox gene regulation. Further analysis, in human anencephaly cases, upregulation of 10 HOX genes was observed, along with aberrant levels of H3K27me3. Notably, HOXB4, HOXC4 and HOXD1 expression was negatively correlated with H3K27me3 levels. Conclusion Our results indicate that abnormal HOX gene expression induced by aberrant H3K27me3 levels may be a risk factor for NTDs and highlight the need for further analysis of genome-wide epigenetic modification in NTDs.

Intervertebral disc degeneration (IDD) is the pathological basis of disc degenerative diseases (DDD). Reduction in the number of cells and degeneration of the extracellular matrix (ECM) in the nucleus pulposus (NP) are characteristics of IDD. Bio-hydrogel combined with stem cell transplantation is a promising treatment. Injectable ECM hydrogels have good biological activity and in-situ gelatinization. However, its biomechanics and stability are insufficient to provide adequate mechanical support for intervertebral discs and to maintain the long-term differential stimulus for seeded stem cells. In our study, we developed genipin cross-linked decellularized nucleus pulposus hydrogel (GDH) as delivery system. We evaluated the mechanical properties, stability, biocompatibility, and differentiation induction of GDH cross-linked with different concentrations of genipin in vitro. The GDH-loaded adipose-derived mesenchymal stem cells (ADSCs) (GDHA) were injected into the rat degenerated coccygeal intervertebral disc. The effect of intervertebral disc regeneration in vivo was evaluated. The results showed that GDH with 0.02% of genipin had similar elastic modulus to human nucleus pulposus, good biocompatibility, and inducibility of expressing NP-related genes. In vivo studies showed that GDHA improved the survival of ADSCs and improved the intervertebral height, MRI index, and histological grading score. In conclusion, GDH, as an outstanding bio-hydrogel cell delivery system, has the therapeutic potential for retarding IDD.

Moving target indication (MTI) based on space–time adaptive processing (STAP) has been widely used in airborne radar due to its ability for clutter suppression performance. However, the existing MTI methods suffer from the problems of insufficient training samples and low detection probability in a non-homogeneous clutter environment. To address these issues, this paper proposes a novel deep learning framework to improve target indication capability. First, combined with the problems of target indication caused by the non-homogeneous clutter, the clutter-plus-target training dataset was modeled by simulation, where various non-ideal factors, such as aircraft crabbing, array errors and internal clutter motion (ICM), were considered. The dataset considers various realistic situations, making the proposed method more robust. Then, a five-layer two-dimensional convolutional neural network (D2CNN) was designed and applied to learn the clutter and target characteristics distribution. The proposed D2CNN can predict the target with a high resolution to implement an end-to-end moving target indication (ETE-MTI) with a higher detection accuracy. In this D2CNN, the input was obtained by the clutter-plus-target angle-Doppler spectrum with a low-resolution estimated only by a few samples. The label was given by the target angle-Doppler spectrum with a high-resolution obtained by the target’s exact angle and Doppler. Thirdly, the proposed method used a few samples to improve the target indication and detection probability, which solved the problem of insufficient samples in the non-homogeneous clutter environments. To elaborate, the proposed method directly implements ETE-MTI without the support of the conventional STAP algorithm to suppress the clutter. The results verify the validity and the robustness of the proposed ETE-MTI with a few samples in the non-homogeneous and low signal-to-clutter ratio (SCR) environments.

Previous studies have yet to show a consistent effect of severe plastic deformation (SPD) processing on the wear behavior of different metals and alloys. To fill this scientific gap, this study investigated the effect of the cyclic extrusion compression (CEC) process, as one of the prominent SPD techniques, on the wear behavior of AA5052. In addition, the microstructure evolution and mechanical properties of the sample before and after the process were experimentally examined and studied. It was found that the yield and ultimate tensile strength of the AA5052 improved significantly after the first pass, while the elongation-to-failure decreased considerably. Further, the subsequent passes mildly changed the trend of increasing strength and reducing elongation-to-failure. SEM morphology indicated that the ductile mode of the initial annealed alloy changed to a combination of ductile and brittle failure modes, in which the level of the brittle failure mode increased with the addition of passes. TEM observations showed that the grain refinement during the CEC process included the formation of dislocation cell structures, subgrain boundaries, and low-angle grain boundaries, with the subgrain boundaries initially evolving into low-angle grain boundaries and, eventually, due to the imposition of additional plastic strain, into high-angle grain boundaries. Furthermore, the CEC process and its increased number of passes led to a significant improvement in wear resistance due to the enhanced tensile strength achieved through grain refinement. In this regard, the wear mechanism of the initial alloy was a combination of adhesion and delamination, with the plastic deformation bands changing to plowing bands with decreased adhesive wear during the process. Eventually, oxidization was found to be a mechanism contributing to wear under all conditions.

In this study, we aimed to systematically profile global RNA N6-methyladenosine (m6A) modification patterns in a mouse model of diabetic cardiomyopathy (DCM). Patterns of m6A in DCM and normal hearts were analyzed via m6A-specific methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). m6A-related mRNAs were validated by quantitative real-time PCR analysis of input and m6A immunoprecipitated RNA samples from DCM and normal hearts. A total of 973 new m6A peaks were detected in DCM samples and 984 differentially methylated sites were selected for further study, including 295 hypermethylated and 689 hypomethylated m6A sites (fold change (FC) > 1.5, P < 0.05). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analyses indicated that unique m6A-modified transcripts in DCM were closely linked to cardiac fibrosis, myocardial hypertrophy, and myocardial energy metabolism. Total m6A levels were higher in DCM, while levels of the fat mass and obesity-associated (FTO) protein were downregulated. Overexpression of FTO in DCM model mice improved cardiac function by reducing myocardial fibrosis and myocyte hypertrophy. Overall, m6A modification patterns were altered in DCM, and modification of epitranscriptomic processes, such as m6A, is a potentially interesting therapeutic approach.

We employ a nonparametric distribution dynamics approach to examine the long-run trend of particulate matter (PM2.5) air pollution in China. Analysis of the data from 288 Chinese prefectural and above (PAA) level cities over the 2001–2019 period shows evidence of convergence in the estimated long-run distribution of air pollution, which is consistent with Environmental Kuznets Curve hypothesis (EKC). However, presence of strong persistence suggests that convergence process takes considerable time. Conditioning analysis shows that China’s environment policy since 2013 has been successful in driving the air pollution in several cities to converge to a lower level. Furthermore, we uncover a poverty-environment trap in the estimated long-run distribution. Our analysis highlights the need for targeted environmental policies in heterogeneous city clusters in China. Lessons learned from China’s experience can also be useful to policy makers in other developing countries.

Pathological left ventricular hypertrophy (LVH) occurs in response to pressure overload and remains the single most important clinical predictor of cardiac mortality. The molecular pathways in the induction of pressure overload LVH are potential targets for therapeutic intervention. Current treatments aim to remove the pressure overload stimulus for LVH, but do not completely reverse adverse cardiac remodelling. Although numerous molecular signalling steps in the induction of LVH have been identified, the initial step by which mechanical stretch associated with cardiac pressure overload is converted into a chemical signal that initiates hypertrophic signalling remains unresolved. In this study, we show that selective deletion of transient receptor potential melastatin 4 (TRPM4) channels in mouse cardiomyocytes results in an approximately 50% reduction in the LVH induced by transverse aortic constriction. Our results suggest that TRPM4 channel is an important component of the mechanosensory signalling pathway that induces LVH in response to pressure overload and represents a potential novel therapeutic target for the prevention of pathological LVH.

Abstract Background Neural tube defects (NTDs) are common congenital malformations resulting in failure of the neural tube closure during early embryonic development. Although it is known that maternal folate deficiency increases the risk of NTDs, the mechanism remains elusive. Results Herein, we report that histone H2A monoubiquitination (H2AK119ub1) plays a role in neural tube closure. We found that the folate antagonist methotrexate induced H2AK119ub1 in mouse embryonic stem cells. We demonstrated that an increase in H2AK119ub1 downregulated expression of the neural tube closure-related genes Cdx2, Nes, Pax6, and Gata4 in mouse embryonic stem cells under folate deficiency conditions. We also determined that the E3 ligase Mdm2 was responsible for the methotrexate-induced increase in H2AK119ub1 and downregulation of neural tube closure-related genes. Surprisingly, we found that Mdm2 is required for MTX-induced H2A ubiquitination and is recruited to the sites of DSB, which is dependent on DNA damage signaling kinase ATM. Furthermore, folic acid supplementation restored H2AK119ub1 binding to neural tube closure-related genes. Downregulation of these genes was also observed in both brain tissue of mouse and human NTD cases, and high levels of H2AK119ub1 were found in the corresponding NTDs samples with their maternal serum folate under low levels. Pearson correlation analysis showed a significant negative correlation between expression of the neural precursor genes and H2AK119ub1. Conclusion Our results indicate that folate deficiency contributes to the onset of NTDs by altering H2AK119ub1 and subsequently affecting expression of neural tube closure-related genes. This may be a potential risk factor for NTDs in response to folate deficiency.

Abstract Background The P38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in CVB3-induced diseases. We previously demonstrated microRNA-21 has potential inhibitory effect on the MAP2K3 which locates upstream of P38 MAPK and was upregulated in mouse hearts upon CVB3 infection. However, the effect and underlying mechanism of miRNA-21 on CVB3 infection remain unclear. Methods We detected continuous changes of cellular miRNA-21 and P38 MAPK proteins expression profiling post CVB3 infection in vitro within 12 h. P38 MAPK signaling was inhibited by the specific inhibitor, small interfering RNA and miRNA-21 mimic in vitro, CVB3 replication, cell apoptosis rate and proliferation were detected. Viral load in the mice heart, cardiomyocyte apoptosis rate and histological of the heart were also detected in the mice model of viral myocarditis pretreated with miRNA-21-lentivirus. Results We observed significant upregulation of miRNA-21 expression followed by suppression of the MAP2K3/P38 MAPK signaling in CVB3-infected Hela cells. The inactivation of the MAP2K3/P38 MAPK signaling by P38 MAPK specific inhibitor, small interfering RNA against MAP2K3, or miRNA-21 overexpression significantly inhibited viral progeny release from CVB3-infected cells. Mechanistically, when compared with control miRNA, miRNA-21 showed no effect on capsid protein VP1 expression and viral load within host cells, while significantly reversing CVB3-induced caspase-3 activation and cell apoptosis rate, further promoting proliferation of infected cells, which indicates the inhibitory effect of miRNA-21 on CVB3 progeny release. In the in vivo study, when compared with control miRNA, miRNA-21 pretreatment remarkably inactivated the MAP2K3/P38 MAPK signaling in mice and protected them against CVB3 infection as evidenced by significantly alleviated cell apoptosis rate, reduced viral titers, necrosis in the heart as well as by remarkably prolonged survival time. Conclusions miRNA-21 were reverse correlated with P38 MAPK activation post CVB3 infection, miRNA-21 overexpression significantly inhibited viral progeny release and decreased myocytes apoptosis rate in vitro and in vivo, suggesting that miRNA-21 may serve as a potential therapeutic agent against CVB3 infection through targeting the MAP2K3/P38 MAPK signaling.

Abstract Background Neural tube defects (NTDs) are common birth defects involving the central nervous system. Recent studies on the etiology of human NTDs have raised the possibility that epigenetic regulation could be involved in determining susceptibility to them. Results Here, we show that the H2AK119ub1 E3 ligase CUL4B is required for the activation of retinoic acid (RA)-inducible developmentally critical homeobox (HOX) genes in NT2/D1 embryonal carcinoma cells. RA treatment led to attenuation of H2AK119ub1 due to decrease in CUL4B, further affecting HOX gene regulation. Furthermore, we found that CUL4B interacted directly with RORγ and negatively regulated its transcriptional activity. Interestingly, knockdown of RORγ decreased the expression of HOX genes along with increased H2AK119ub1 occupancy levels, at HOX gene sites in N2/D1 cells. In addition, upregulation of HOX genes was observed along with lower levels of CUL4B-mediated H2AK119ub1 in both mouse and human anencephaly NTD cases. Notably, the expression of HOXA10 genes was negatively correlated with CUL4B levels in human anencephaly NTD cases. Conclusions Our results indicate that abnormal HOX gene expression induced by aberrant CUL4B-mediated H2AK119ub1 levels may be a risk factor for NTDs, and highlight the need for further analysis of genome-wide epigenetic modifications in NTDs.

Abstract Background Wilms’ tumor is also called nephroblastoma and is the most common pediatric renal cancer. Several genetic and epigenetic factors have been found to account for the development of Wilms’ tumor. MiRNAs play important roles in this tumorigenic process. In the present study, we aimed to investigate the role of miR-140-5p in nephroblastoma by identifying its targets, as well as its underlying molecular mechanism of action. Methods The miRNA expression profile of nephroblastoma samples was investigated and the targets of miR-140-5p were predicted and validated using the miRNA luciferase reporter method. Moreover, the roles of miR-140-5p in regulating nephroblastoma cell proliferation, migration and cell cycle were analyzed by the CCK8, migration and flow cytometry assays, respectively. The downstream protein of the direct target of miR-140-5p was also identified. Results miR-140-5p was downregulated in Wilms’ tumor tissues, whereas in the nephroblastoma cell lines G401 and WT-CLS1 that exhibited high levels of miRNA-140-5p, inhibition of cellular proliferation and metastasis were noted as well as cell cycle arrest at the G1/S phase. TGFBRI and IGF1R were identified as direct target genes for miRNA-140-5p. In addition, SMAD2/3 and p-AKT were regulated by TGFBRI and IGF1R separately and participated in the miRNA-140-5p regulatory network. Ectopic expression of TGFBR1 and IGF-1R could abrogate the inhibitory effect of miR-140-5p. Conclusion We demonstrated that miRNA-140-5p participates in the progression of Wilms’ tumor by targeting the TGFBRI/SMAD2/3 and the IGF-1R/AKT signaling pathways.

Deceptive jamming may not only induce a large amount of false alarms and deteriorate the target detection performance, but also lead to degraded space-time adaptive processing (STAP) performance in an airborne radar. To tackle these issues, this paper proposes a cognitive transmitting scheme to counter the deceptive jamming for airborne array radar. The proposed approach is composed of two steps. The first step is the deceptive jamming perception. A specially designed high pulse repetition frequency (PRF) waveform is transmitted, and then the deceptive jamming is identified according to the angle clustering feature of the false targets. In the second step, the phase-only transmit pattern with notches at the jammers' directions is designed. The encountered pattern synthesis problem is nonconvex due to the fixed excitations constraint. To solve this problem, a nested alternating direction method of multipliers (N-ADMM) is proposed. With the developed approach, the radiated power at the jammers' directions is attenuated significantly. Therefore, the probing signal possesses the characteristic of low probability of intercept (LPI). Numerical examples are given to demonstrate the effectiveness of the proposed approach.

Sparse Bayesian learning-based space–time adaptive processing (SBL-STAP) algorithms can achieve superior clutter suppression performance with limited training sample support in practical heterogeneous and non-stationary clutter environments. However, when the system has high degrees of freedom (DOFs), SBL-STAP algorithms suffer from high computational complexity, since the large-scale matrix calculations and the inversion operations of large-scale covariance matrices are involved in the iterative process. In this article, we consider a computationally efficient implementation for SBL-STAP algorithms. The efficient implementation is based on the fact that the covariance matrices that need to be updated in the iterative process of the SBL-STAP algorithms have a Hermitian Toplitz-block-Toeplitz (HTBT) structure, with the result being that the inverse covariance matrix can be expressed in closed form by using a special case of the Gohberg–Semencul (G-S) formula. Based on the G-S-type factorization of the inverse covariance matrix and the structure of the used dictionary matrix, we can perform almost all operations in the SBL-STAP algorithms by 2-D FFT/IFFT. As a result, compared with the original SBL-STAP algorithms, even for moderate data sizes, the proposed algorithms can directly reduce the computational load by about two orders of magnitudes without any performance loss. Finally, simulation results validate the effectiveness of the proposed algorithms.

For millimeter-wave (MMW) imaging security systems, the image resolution promisingly determines the performance of suspicious target detection and recognition. Conventional synthetic aperture radar (SAR) imaging algorithms only provide limited resolution in active MMW imaging, which is limited by the system. In terms of enhancing the resolution of a region of interest (ROI) image containing suspicious targets, super-resolution (SR) imaging is adopted via Bayesian compressive sensing (BCS) implemented by fast Fourier transform (FFT). The spatial sparsity of MMW ROI images is well exploited with BCS to achieve resolution enhancement without computational cost. Both simulated and measured experiments confirm that the proposed scheme effectively improves the resolution of ROI images.

Background The severe plastic deformation approach and its well-known cyclic extrusion compression (CEC) method have been established as a powerful tool for fabricating bulk ultrafine-grained metals and alloys with improved properties. Objective This study focused on the microstructure evolution, hardness behavior, and corrosion properties of the CEC-processed Al5052 up to four passes compared to the initial annealed state. Methods The initial and CEC-processed Al5052 samples at different pass numbers were examined experimentally by EBSD analyses, hardness measurements, and corrosion resistance. Results Substantial grain refinement was attained from ~23 μm for the annealed sample to ~0.8 μm in the four passes sample. In addition, the hardness values considerably increased up to 75.7% after four passes from the initial value of 80 HV. In addition, the increment of pass numbers led to a more uniform dispersion of hardness values. Furthermore, the production of more stable protective oxide layers on the UFG structure of the CEC-processed sample led to the improvement in electrochemical response with a corrosion rate reduction from 1.49 to 1.02 mpy, respectively, in the annealed and final pass CEC-processed samples. In fact, the annealed sample manifested more large-sized and deeper pits than the CECed samples due to the increment of potential values and electrochemical attack of chlorine ions that finally deteriorates the corrosion performance. Conclusions CEC is an efficient method to improve the mechanical properties of materials due to substantial microstructural changes along with enhancement of electrochemical behavior because of the presence of small-sized and shallow pits.

RationaleGq-coupled receptors are thought to play a critical role in the induction of left ventricular hypertrophy (LVH) secondary to pressure overload, although mechano-sensitive channel activation by a variety of mechanisms has also been proposed, and the relative importance of calcineurin- and calmodulin kinase II (CaMKII)-dependent hypertrophic pathways remains controversial.ObjectiveTo determine the mechanisms regulating the induction of LVH in response to mechanical pressure overload.Methods and ResultsTransgenic mice with cardiac-targeted inhibition of Gq-coupled receptors (GqI mice) and their non-transgenic littermates (NTL) were subjected to neurohumoral stimulation (continuous, subcutaneous angiotensin II (AngII) infusion for 14 days) or mechanical pressure overload (transverse aortic arch constriction (TAC) for 21 days) to induce LVH. Candidate signaling pathway activation was examined. As expected, LVH observed in NTL mice with AngII infusion was attenuated in heterozygous (GqI+/–) mice and absent in homozygous (GqI–/–) mice. In contrast, LVH due to TAC was unaltered by either heterozygous or homozygous Gq inhibition. Gene expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and α-skeletal actin (α-SA) was increased 48 h after AngII infusion or TAC in NTL mice; in GqI mice, the increases in ANP, BNP and α-SA in response to AngII were completely absent, as expected, but all three increased after TAC. Increased nuclear translocation of nuclear factor of activated T-cells c4 (NFATc4), indicating calcineurin pathway activation, occurred in NTL mice with AngII infusion but not TAC, and was prevented in GqI mice infused with AngII. Nuclear and cytoplasmic CaMKIIδ levels increased in both NTL and GqI mice after TAC but not AngII infusion, with increased cytoplasmic phospho- and total histone deacetylase 4 (HDAC4) and increased nuclear myocyte enhancer factor 2 (MEF2) levels.ConclusionCardiac Gq receptors and calcineurin activation are required for neurohumorally mediated LVH but not for LVH induced by mechanical pressure overload (TAC). Rather, TAC-induced LVH is associated with activation of the CaMKII-HDAC4-MEF2 pathway.

Aluminum and its alloys having lots of advantageous properties are among the most-used metallic materials. So, it is of immense importance to find suitable processes and methods leading to high-quality purified Al melt. In this regard, there are numerous challenges in achieving high purity Al melts, such as its propensity to react with air, oxygen, and water vapor, the presence of a variety of oxide, non-oxide, and solid particle inclusions that lead to the production of pores, cracks, pinholes, and dross, finally adversely influencing the overall quality of the product. The main methods of melt refining are fluxing, floatation, and filtration, but more sophisticated methods have also emerged. The best method for purification can be chosen based on the type of impurities and the desired level of purification. With the industrial development, the need to establish more cost-effective and simpler methods has increased, and in addition, methods should be considered for recycling large volumes of scarp Al parts that contain more impurities. Moreover, achieving high purity melt is also a vital issue for use in specific applications. The present article has been written to discuss the above issues and focus on the study of various methods of aluminum purification.

Aluminum alloys, especially the 5000 series, have drawn the attention of the transportation industry due to their lightweight and consequently reduced fuel consumption. In this regard, one of the major problems of this alloy is its low strength and ductility that can be solved using rolling and post-annealing. Accordingly, the present study concentrates on this issue. Microstructural images showed that the rolling process develops a lot of tangled and trapped dislocations in the sample, which gradually lead to the formation of dislocation bundles and networks. Subsequent annealing can produce a more homogeneous structure with clear grain boundaries and low dislocation density in the inner region of the grains. However, grain refinement efficiency through rolling is retained even after annealing. Initial and rolled Al5052 with the maximum intensity of 2.87 and 6.33 possess the lowest and highest overall texture. Also, post-annealing decreases the texture intensity to 6.33 and 4.87 at 150 and 200 °C, respectively. In this context, deformation texture components strengthen considerably after the rolling process due to the formation of shear bands, and they slightly weaken during heat treatment. Although the initial annealing of the as-received material does not cause discontinuous recrystallization during rolling, it may facilitate the material recovery before rolling. Post-annealing was found to decrease the improved effect of strength by rolling and increase the negative influence of ductility due to the inhibition of dislocation strengthening. The results showed that both dislocation density and the precipitation of Mg atoms are influential for electrical resistivity.

Abstract Background Interleukin (IL)-37 has emerged as a novel anti-inflammatory cytokine that play an immunosuppressive role in regulating inflammatory response. This study aimed to measure IL-37 levels in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with systemic juvenile idiopathic arthritis (sJIA), and to establish the correlation between IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines. Methods The mRNA levels of IL-37 in PBMCs and plasma IL-37 concentrations in 46 sJIA patients and 30 age- and sex-matched healthy controls were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations between plasma IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines in sJIA were analyzed by Spearman correlation test. PBMCs from the sJIA patients were stimulated with recombinant human IL-37 (rhIL-37) protein, expressions of IL-1β, IL-6, TNF-α and IL-17 were detected by RT-PCR and ELISA. Results Plasma levels of IL-37 and relative IL-37 mRNA expression were significantly elevated in sJIA patients, especially in active sJIA patients, when compared with the healthy controls (P

Abstract Background The pollen wall, which protects male gametophyte against various stresses and facilitates pollination, is essential for successful reproduction in flowering plants. The pollen wall consists of gametophyte-derived intine and sporophyte-derived exine. From outside to inside of exine are tectum, bacula, nexine I and nexine II layers. How these structural layers are formed has been under extensive studies, but the molecular mechanisms remain obscure. Results Here we identified two osabcg3 allelic mutants and demonstrated that OsABCG3 was required for pollen development in rice. OsABCG3 encodes a half-size ABCG transporter localized on the plasma membrane. It was mainly expressed in anther when exine started to form. Loss-function of OsABCG3 caused abnormal degradation of the tapetum. The mutant pollen lacked the nexine II and intine layers, and shriveled without cytoplasm. The expression of some genes required for pollen wall formation was examined in osabcg3 mutants. The mutation did not alter the expression of the regulatory genes and lipid metabolism genes, but altered the expression of lipid transport genes. Conclusions Base on the genetic and cytological analyses, OsABCG3 was proposed to transport the tapetum-produced materials essential for pollen wall formation. This study provided a new perspective to the genetic regulation of pollen wall development.