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Abstract Semen Ziziphi Spinosae (SZS) is a traditional Chinese herbal medicine widely used to treat insomnia and anxiety in clinical practice. Currently, the demand for SZS is increasing every year, but the production of wild SZS is unstable due to environmental factors. Grafting sour jujube scions onto sour jujube or jujube tree stocks can achieve a high production rate within a short period of time. However, the effects of grafting on the quality of SZS have not been reported. This study investigated the differences between wild-type and grafted SZS from three aspects: phenotype, chemical composition, and molecular mechanism. The findings revealed that the grafted specimens were generally larger in morphology and lighter in color than the wild-type samples. The dimensions of both the grafted specimens were generally larger than those of the wild specimens. The HPLC-ELSD results revealed that the three main chemical components in the grafted SZS, namely, spinosin, jujuboside A, and jujuboside B, had higher contents than their wild-type counterparts. Comprehensive transcriptome sequencing analysis and KEGG annotation revealed that DEG enrichment between grafted and wild-type SZS occurred mainly during stress resistance and rootstock scion healing. There were 23 DEGs that may encode enzymes involved in the biosynthetic pathway of flavonoids and 21 genes encoding terpenoid saponins. Further investigation revealed that the expression of the genes C4H, CHS, CHI, and F3’5’H in the flavonoid biosynthesis pat.hway and HMGR, MVK, MVD, and FPPS in the saponin biosynthesis pathway accounted for the difference in quality between grafted and wild SZS. Furthermore, WGCNA identified 15 core genes related to medicinal ingredients between grafted and wild SZS. These results provide support for further research on the differences in the quality of medicinal ingredients between grafted and wild SZS.

Abstract Telomerase reverse transcriptase (Tert) has been found to have a protective effect on telomeric DNA, but whether it could improve the repair of reactive oxygen species (ROS)-induced DNA damage and promote myocardial regenerative repair after myocardial infarction (MI) by protecting telomeric DNA is unclear. The immunofluorescence staining with TEL-CY3 and the TeloTAGGG Telomerase PCR ELISA kit were used to show the telomere length and telomerase activity. The heart-specific Tert-deletion homozygotes were generated by using commercial Cre tool mice and flox heterozygous mice for mating. We measured the telomere length and telomerase activity of mouse cardiomyocytes (CMs) at different days of age, and the results showed that they were negatively correlated with age. Overexpressed Tert could enhance telomerase activity and lengthen telomeres, thereby repairing the DNA damage induced by ROS and promoting CM proliferation in vitro. The in vivo results indicated that enhanced Tert could significantly improve cardiac function and prognosis by alleviating CM DNA damage and promoting angiogenesis post-MI. In terms of mechanism, DNA pulldown assay was used to identify that nuclear ribonucleoprotein A2B1 (hnRNPA2B1) could be an upstream regulator of Tert in CMs. Overexpressed Tert could activate the NF-κB signaling pathway in CMs and bind to the VEGF promoter in the endothelium to increase the VEGF level. Further immunoblotting showed that Tert protected DNA from ROS-induced damage by inhibiting ATM phosphorylation and blocking the Chk1/p53/p21 pathway activation. HnRNPA2B1-activated Tert could repair the ROS-induced telomeric DNA damage to induce the cell cycle re-entry in CMs and enhance the interaction between CMs and endothelium, thus achieving cardiac regenerative repair after MI.

Doxorubicin (DOX)-mediated cardiotoxicity can impair the clinical efficacy of chemotherapy, leading to heart failure (HF). Given the importance of circRNAs and miRNAs in HF, this paper intended to delineate the mechanism of the circular RNA 0006332 (circ -0,006,332)/microRNA (miR)-143/Toll-like receptor 2 (TLR2) axis in doxorubicin (DOX)-induced HF. The binding of miR-143 to circ -0,006,332 and TLR2 was assessed with the dual-luciferase assay, and the binding between miR-143 and circ -0,006,332 was determined with FISH, RIP, and RNA pull-down assays. miR-143 and/or circ -0,006,332 were overexpressed in rats and cardiomyocytes, followed by DOX treatment. In cardiomyocytes, miR-143 and TLR2 expression, cell viability, LDH release, ATP contents, and levels of IL-1β, IL-18, TNF-α, and pyroptosis-related molecules were examined. In rats, cardiac function, serum levels of cardiac enzymes, apoptosis, myocardial fibrosis, and levels of IL-1β, IL-18, TNF-α, TLR2, and pyroptosis-related molecules were detected. miR-143 diminished TLR2 expression by binding to TLR2, and circ -0,006,332 bound to miR-143 to downregulate miR-143 expression. miR-143 expression was reduced and TLR2 expression was augmented in DOX-induced cardiomyocytes. miR-143 inhibited DOX-induced cytotoxicity by suppressing pyroptosis in H9C2 cardiomyocytes. In DOX-induced rats, miR-143 reduced cardiac dysfunction, myocardial apoptosis, myocardial fibrosis, TLR2 levels, and pyroptosis. Furthermore, overexpression of circ -0,006,332 blocked these effects of miR-143 on DOX-induced cardiomyocytes and rats. Circ -0,006,332 stimulates cardiomyocyte pyroptosis by downregulating miR-143 and upregulating TLR2, thus promoting DOX-induced cardiac injury.

Abstract Mangiferin (MAN) was a natural bioactive xanthone with remarkable antioxidative, anti‐inflammatory, and antiapoptotic effects. The purpose of this study to determine the protective influence of MAN on D‐galactose (D‐gal)‐induced aging and cognitive impairment, together with its underlying molecular mechanism. The network pharmacology molecular docking analysis revealed that MAN has a potential binding with aging‐related oxidative stress and apoptosis proteins. In D‐gal‐induced aging mice, MAN could significantly reduce D‐gal‐induced histopathological changes of liver and brain tissues. Moreover, MAN administration obviously increased activities of antioxidant enzymes (SOD, T‐AOC, GSH‐Px, and CAT) and decreased levels of AChE and MDA in the serum, liver, or brain tissues. Additionally, MAN alleviated learning and memory disorders and improved the exploration ability. Western blotting and immunohistochemical analysis results revealed that MAN could regulate the expressions of PI3K/Akt/Nrf2 signaling pathway‐related proteins and apoptotic‐related proteins (Bax, Bcl‐2, and Caspase‐9) in the liver tissues. Therefore, these findings suggested that MAN can be used as a potent dietary supplement in functional foods for the protection against aging‐related impairments.

Background: Mental health issues are increasingly prominent worldwide, posing significant threats to patients and deeply affecting their families and social relationships. Traditional diagnostic methods are subjective and delayed, indicating the need for an objective and effective early diagnosis method. Methods: To this end, this paper proposes a lightweight detection method for multi-mental disorders with fewer data sources, aiming to improve diagnostic procedures and enable early patient detection. First, the proposed method takes Electroencephalography (EEG) signals as sources, acquires brain rhythms through Discrete Wavelet Decomposition (DWT), and extracts their approximate entropy, fuzzy entropy, permutation entropy, and sample entropy to establish the entropy-based matrix. Then, six kinds of conventional machine learning classifiers, including Support Vector Machine (SVM), k-Nearest Neighbors (kNN), Naive Bayes (NB), Generalized Additive Model (GAM), Linear Discriminant Analysis (LDA), and Decision Tree (DT), are adopted for the entropy-based matrix to achieve the detection task. Their performances are assessed by accuracy, sensitivity, specificity, and F1-score. Concerning these experiments, three public datasets of schizophrenia, epilepsy, and depression are utilized for method validation. Results: The analysis of the results from these datasets identifies the representative single-channel signals (schizophrenia: O1, epilepsy: F3, depression: O2), satisfying classification accuracies (88.10%, 75.47%, and 89.92%, respectively) with minimal input. Conclusions: Such performances are impressive when considering fewer data sources as a concern, which also improves the interpretability of the entropy features in EEG, providing a reliable detection approach for multi-mental disorders and advancing insights into their underlying mechanisms and pathological states.

Short-cycle agricultural product sales forecasting significantly reduces food waste by accurately predicting demand, ensuring producers match supply with consumer needs. However, the forecasting is often subject to uncertain factors, resulting in highly volatile and discontinuous data. To address this, a hierarchical prediction model that combines RF-XGBoost is proposed in this work. It adopts the Random Forest (RF) in the first layer to extract residuals and achieve initial prediction results based on correlation features from Grey Relation Analysis (GRA). Then, a new feature set based on residual clustering features is generated after the hierarchical clustering is applied to classify the characteristics of the residuals. Subsequently, Extreme Gradient Boosting (XGBoost) acts as the second layer that utilizes those residual clustering features to yield the prediction results. The final prediction is by incorporating the results from the first layer and second layer correspondingly. As for the performance evaluation, using agricultural product sales data from a supermarket in China from 1 July 2020 to 30 June 2023, the results demonstrate superiority over standalone RF and XGBoost, with a Mean Absolute Percentage Error (MAPE) reduction of 10% and 12%, respectively, and a coefficient of determination (R2) increase of 22% and 24%, respectively. Additionally, its generalization is validated across 42 types of agricultural products from six vegetable categories, showing its extensive practical ability. Such performances reveal that the proposed model beneficially enhances the precision of short-term agricultural product sales forecasting, with the advantages of optimizing the supply chain from producers to consumers and minimizing food waste accordingly.

IntroductionVariation in plant nitrogen uptake rate and substrate preference is complicated due to the combined influence of abiotic and biotic factors. For the same species of tree across different ages, the interactions between root structural traits, nitrogen uptake rate, and soil environment have not been fully characterized, a situation that constrains our understanding of underground resource strategies employed by trees at different ages.MethodsIn the present study, we examined the nitrogen uptake rate, mycorrhiza, morphology, architecture, and chemistry of the roots of Larix principis-rupprechtii in a chronosequence (aged 18, 27, 37, 46, and 57 years) in the Saihanba Mechanical Forest Farm in Northern China.ResultsL. principis-rupprechtii preferred to absorb ammonium, followed in order by glycine and nitrate. The ammonium uptake rate of L. principis-rupprechtii significantly decreased (aged 18–37 years) and then increased (aged 46–57 years) with tree age. The glycine, nitrate, and total nitrogen uptake rates decreased with tree age. The root resource acquisition strategy appeared to shift from an acquisitive strategy to a conservative strategy associated with increasing tree age.DiscussionAlong the root-mycorrhizal collaboration gradient, the younger L. principis-rupprechtii relied more on their own root morphology and physiology to acquire resources, adopting a “do it yourself” strategy comprising increasing the specific root length, the specific root area, and the N uptake rate (nitrate and glycine). Conversely, older trees depended more on mycorrhizal partners to acquire nitrogen resources, an “outsourcing” strategy. The results contribute to our understanding of underground resource-use strategies of plants and the nitrogen cycle in forest ecosystems according to stand age.

Introduction: Extracellular vesicles (EVs)-mediated cell-to-cell communication is crucial for hypoxia-induced cell proliferation and tissue repair, but its function in endogenous cardiac regeneration is still unknown. Objectives: Herein, we aimed to determine whether hypoxia-inducible circWhsc1 in endothelial EVs promoted cardiomyocyte (CM) proliferation and cardiac regeneration. Methods: RNA-sequence data was used to identify EV circRNAs that were involved into endogenous cardiac regeneration. Quantitative polymerase chain reactions were conducted to determine circRNA expression in tissue, cells and EVs. Gain- and loss-of-function assays were performed to explore the function of EV-derived circWhsc1 during cardiac regeneration. Western blotting and RNA pulldown assays were used to investigate its underlying mechanism. Results: We found that circWhsc1 was enriched in neonatal mouse hearts, particularly in cardiac ECs, and was further upregulated both in ECs and EC-derived EVs under hypoxic conditions. When cocultured with hypoxia-preconditioned neonatal ECs or their secreted EVs, both neonatal and adult CMs exhibited an increased proliferation rate and G2/M ratio, which could be attenuated by knockdown of circWhsc1 in ECs. In vivo, EC-restricted overexpression of circWhsc1 and EV-mediated delivery of circWhsc1 induced CM proliferation, alleviated cardiac fibrosis and restored cardiac function following myocardial infarction in adult mice. Mechanistic studies revealed that EV-derived circWhsc1 activated TRIM59 by enhancing its phosphorylation, thereby reinforcing the binding of TRIM59 to STAT3, phosphorylating STAT3 and inducing CM proliferation. Conclusion: The current study demonstrated that hypoxia-inducible circWhsc1 in EC-derived EVs induces CM proliferation and heart regeneration. EC-CM communication mediated by EV-derived circWhsc1 might represent a prospective therapeutic target for inducing cardiac repair post-myocardial infarction.

Plants produce a range of carbohydrates to meet their growth and developmental needs. Protein reversible phosphorylation plays key roles in coordinating multiple metabolic pathways and integrating diverse internal and external cues. Understanding such regulatory metabolism will provide novel resources for breeding and crop management by modulating metabolic pathways for control of growth and stress response. In this review, we summarize the complex, multifaceted functions of protein phosphorylation and their connections to plant metabolism. We focus particularly on carbohydrate metabolic pathways that are controlled by key kinases and discuss how they are linked to downstream changes in physiology, important agronomic traits and crop quality.

Abstract Accurate clinical diagnosis of the stage of tumor development is essential for formulating a treatment plan. However, the stage of tongue tumor development among malignant, benign and leukoplakia is easily misdiagnosed, resulting differing treatment approaches, taking patients in danger and preventing them from receiving the deserved care. This study aimed to establish an automatic recognition system for tongue tumors at different stages of development using artificial intelligence methods along with pathological tissue section images. By improving Swin Transformer framework, a new framework in deep learning, the tissue slice image is used to identify the lesion and non‐lesion areas by the patch‐based method, and then an output is reconstructed by self‐Assembly method that the lesion areas is marked with heat map. Subsequently, an automatic recognition system with a friendly page is designed for the stage of tongue tumor development (malignant, benign, and leukoplakia). The proposed model has a high recognition accuracy (98.45%). The prediction accuracy of each category of the system is higher than that of specialist doctors with 13 years of experience. The Swin Transformer framework was improved in this study to accurately and automatically identify the various stages of tongue tumor development.

Abstract Distant metastasis (DM) is relatively uncommon in T1 stage gastric cancer (GC). The aim of this study was to develop and validate a predictive model for DM in stage T1 GC using machine learning (ML) algorithms. Patients with stage T1 GC from 2010 to 2017 were screened from the public Surveillance, Epidemiology and End Results (SEER) database. Meanwhile, we collected patients with stage T1 GC admitted to the Department of Gastrointestinal Surgery of the Second Affiliated Hospital of Nanchang University from 2015 to 2017. We applied seven ML algorithms: logistic regression, random forest (RF), LASSO, support vector machine, k-Nearest Neighbor, Naive Bayesian Model, Artificial Neural Network. Finally, a RF model for DM of T1 GC was developed. The AUC, sensitivity, specificity, F1-score and accuracy were used to evaluate and compare the predictive performance of the RF model with other models. Finally, we performed a prognostic analysis of patients who developed distant metastases. Independent risk factors for prognosis were analysed by univariate and multifactorial regression. K-M curves were used to express differences in survival prognosis for each variable and subvariable. A total of 2698 cases were included in the SEER dataset, 314 with DM, and 107 hospital patients were included, 14 with DM. Age, T-stage, N-stage, tumour size, grade and tumour location were independent risk factors for the development of DM in stage T1 GC. A combined analysis of seven ML algorithms in the training and test sets found that the RF prediction model had the best prediction performance (AUC: 0.941, Accuracy: 0.917, Recall: 0.841, Specificity: 0.927, F1-score: 0.877). The external validation set ROCAUC was 0.750. Meanwhile, survival prognostic analysis showed that surgery (HR = 3.620, 95% CI 2.164–6.065) and adjuvant chemotherapy (HR = 2.637, 95% CI 2.067–3.365) were independent risk factors for survival prognosis in patients with DM from stage T1 GC. Age, T-stage, N-stage, tumour size, grade and tumour location were independent risk factors for the development of DM in stage T1 GC. ML algorithms had shown that RF prediction models had the best predictive efficacy to accurately screen at-risk populations for further clinical screening for metastases. At the same time, aggressive surgery and adjuvant chemotherapy can improve the survival rate of patients with DM.

Cardiac repair after myocardial infarction (MI) is orchestrated by multiple intrinsic mechanisms in the heart. Identifying cardiac cell heterogeneity and its effect on processes that mediate the ischemic myocardium repair may be key to developing novel therapeutics for preventing heart failure. With the rapid advancement of single-cell transcriptomics, recent studies have uncovered novel cardiac cell populations, dynamics of cell type composition, and molecular signatures of MI-associated cells at the single-cell level. In this review, we summarized the main findings during cardiac repair by applying single-cell transcriptomics, including endogenous myocardial regeneration, myocardial fibrosis, angiogenesis, and the immune microenvironment. Finally, we also discussed the integrative analysis of spatial multi-omics transcriptomics and single-cell transcriptomics. This review provided a basis for future studies to further advance the mechanism and development of therapeutic approaches for cardiac repair.

Transplantation of helpful bacteria has been used to treat disease through modulating host microbiota. Here, the authors report a strategy to control bacteria localization in the jejunum, via an in vivo in-situ thiol-disulfide exchange reaction between surface-reactive bacteria and mucous.

Narrow emission lines in a galaxy’s spectrum that show double peaks indicate the presence of distinct gas components with different velocities, and its physical origin remains uncertain. This study uses galaxies from the final MaNGA data release to detect double-peaked narrow emission-line spaxels (DPSs) by examining the double Gaussian profiles of the H α -[N ii ] doublets across all MaNGA spaxels. A total of 5420 DPSs associated with 304 double-peaked narrow emission-line galaxies (DPGs) are identified, with each DPG containing a minimum of five DPSs and being free from overlap with other galaxies. We find that DPSs can be categorized into three groups according to their central distance r / R _e and the velocity difference Δ v between their two components: the inner low-Δ v , inner high-Δ v , and outer DPSs. By incorporating the physical characteristics of the DPGs into their DPSs, we demonstrate for the first time the existence of statistical correlations between barred DPGs and inner low-Δ v DPSs, AGN-hosting DPGs, and inner high-Δ v DPSs, as well as tidal DPGs and outer DPSs.

In NGC 2992, a galaxy-scale ionized gas outflow driven by active galactic nuclei (AGNs) has long been recognized, yet its impact on the host galaxy has remained elusive. In this paper, we utilize data from the archival Very Large Telescope/MUSE to present a spatially resolved analysis of stellar populations in this galaxy. Two different stellar population templates are employed to fit the stellar continuum, allowing us to determine the light-weighted stellar age, metallicity, the fraction of the young stellar population (age

Quiescent galaxies generally possess denser cores than star-forming galaxies with similar mass. As a measurement of the core density, the central stellar mass surface density within a radius of 1 kpc (Σ _1 ) was thus suggested to be closely related to galaxy quenching. Massive star-forming galaxies with high Σ _1 do not fit into this picture. To understand the origin of such galaxies, we compare the spatially resolved stellar population and star formation properties of massive (>10 ^10.5 M _⊙ ) blue spiral galaxies with high and low Σ _1 , divided by Σ _1 = 10 ^9.4 M _⊙ kpc ^−2 , based on the final release of MaNGA integral field unit data. We find that both high-Σ _1 and low-Σ _1 blue spirals show large diversities in stellar population and star formation properties. Despite the diversities, high-Σ _1 blue spirals are statistically different from the low-Σ _1 ones. Specifically, the radial profiles of the luminosity-weighted age and Mgb/〈Fe〉 show that high-Σ _1 blue spirals consist of a larger fraction of galaxies with younger and less α -element-enhanced centers than their low-Σ _1 counterparts, ∼55% versus ∼30%. The galaxies with younger centers mostly have higher central specific star formation rates, which still follow the spaxel-based star formation main-sequence relation. Examinations of the H α velocity field and the optical structures suggest that galactic bars or galaxy interactions should be responsible for the rejuvenation of these galaxies. The remaining ∼45% of high-Σ _1 blue spirals are consistent with the inside-out growth scenario.

Objective To use data from the Global Burden of Disease (GBD) Study 2019 to report the global, regional and national rates and trends of annual incidence, point prevalence and years lived with disability (YLD) for gout in adolescents and young adults aged 15–39 years.Methods We conducted a serial cross-sectional study of gout burden in the young population aged 15–39 years using data from GBD Study 2019. We extracted rates per 100 000 population of incidence, prevalence and YLD of gout, then calculated their average annual percentage changes (AAPCs) at the global, regional and national level between 1990 and 2019 by sociodemographic index (SDI).Results The global gout prevalent cases in individuals aged 15–39 years was 5.21 million in 2019, with the annual incidence substantially increasing from 38.71 to 45.94 per 100 000 population during 1990–2019 (AAPC 0.61, 95% CI 0.57 to 0.65). This substantial increase was observed in all SDI quintiles (low, low-middle, middle, high-middle and high) and every age subgroup (15–19, 20–24, 25–29, 30–34 and 35–39 years). Males accounted for 80% of the gout burden. High-income North America and East Asia were facing a substantial increase in gout incidence and YLD simultaneously. Elimination of high body mass index can reduce 31.74% of the gout YLD globally in 2019, which varied from 6.97% to 59.31% regionally and nationally.Conclusion Gout incidence and YLD in the young population grew simultaneously and substantially in both developed and developing countries. Improving representative national-level data on gout, interventions for obesity and awareness in young populations are strongly suggested.

Abstract Objectives Doxorubicin (DOX) can contribute to severe myocardial injury, and bone marrow stromal cells (BMSC)‐exosomes (Exos) improves acute myocardial infarction. Hence, this research investigated whether BMSC‐Exos alleviated DOX‐induced myocardial injury. Methods BMSC‐derived Exos were isolated and identified, and the optimal concentration of DOX was confirmed. H9C2 cells were treated with DOX and BMSC‐Exos or in combination with the protein kinase B (AKT) inhibitor. Reactive oxygen species (ROS) and JC‐1 were detected to assess oxidative stress (OS) and mitochondrial membrane damage, respectively. In addition, the expression of pyroptosis‐related molecules was measured. The expression of phosphatidylinositol 3 kinase (PI3K)‐AKT pathway‐related proteins and the phosphorylation and acetylation of forkhead box O1 (Foxo1) in the cell nucleus and cytoplasm were tested. Last, interactions between Foxo1 and gasdermin D (GSDMD) were assessed. Results BMSC‐Exo treatment increased viability and mitochondrial membrane potential and reduced lactic dehydrogenase release and ROS levels in DOX‐treated H9C2 cells. Furthermore, the addition of BMSC‐Exos suppressed DOX‐induced activation and upregulation of NLRP3 and apoptosis‐associated speck‐like protein containing A CARD (ASC) and in vitro cleavage of caspase‐1, GSDMD, interleukin (IL)‐1β, and IL‐18 proteins. Additionally, BMSC‐Exo treatment enhanced the expression of phosphorylated (p)‐PI3K, p‐AKT, and p‐mTOR in DOX‐treated H9C2 cells and the levels of phosphorylated Foxo1 in the cytoplasm of DOX‐treated H9C2 cells. Foxo1 was enriched in the promoter region of GSDMD. Moreover, the AKT inhibitor API‐2 annulled the effects of BMSC‐Exos on OS, pyroptosis, and Foxo1 phosphorylation in DOX‐treated H9C2 cells. Conclusions BMSC‐Exos phosphorylated Foxo1 and inactivated Foxo1 transcription via the PI3K‐AKT pathway to diminish GSDMD expression, thus restraining DOX‐induced pyroptosis and OS of myocardial cells.

A highly efficient redox- and step-economic method to synthesize N,O- and O,O-difluoroboron complexes from alkynes under aqueous condition with HBF4 as BF2 source has been developed. This strategy features good yields, broad substrate scope, mild reaction conditions, readily available starting materials and gram-scale synthesis. Significantly, these difluoroboron complexes present good fluorescence properties, indicating their potential applications in luminescent materials.

Plasmodiophora brassicae (Wor.) is an obligate plant pathogen affecting Brassicae worldwide. To date, there is very little information available on the biology and molecular basis of P. brassicae primary and secondary zoospore infections. To examine their roles, we used microscope to systematically investigate the infection differences of P. brassicae between samples inoculated separately with resting spores and secondary zoospores. The obvious development of P. brassicae asynchrony that is characterized by secondary plasmodium, resting sporangial plasmodium, and resting spores was observed at 12 days in Brassica rapa inoculated with resting spores but not when inoculated with secondary zoospores at the same time. Inoculation with resting spores resulted in much more development of zoosporangia clusters than inoculation with secondary zoospores in non-host Spinacia oleracea. The results indicated that primary zoospore infection played an important role in the subsequent development. To improve our understanding of the infection mechanisms, RNA-seq analysis was performed. Among 18 effectors identified in P. brassicae, 13 effectors were induced in B. rapa seedlings inoculated with resting spores, which suggested that the pathogen and host first contacted, and more effectors were needed. Corresponding to those in B. rapa, the expression levels of most genes involved in the calcium-mediated signaling pathway and PTI pathway were higher in plants inoculated with resting spores than in those inoculated with secondary zoospores. The ETI pathway was suppressed after inoculation with secondary zoospores. The genes induced after inoculation with resting spores were suppressed in B. rapa seedlings inoculated with secondary zoospores, which might be important to allow a fully compatible interaction and contribute to a susceptible reaction in the host at the subsequent infection stage. The primary zoospores undertook an more important interaction with plants.

Aims: Metabolic switching during heart development contributes to postnatal cardiomyocyte (CM) cell cycle exit and loss of regenerative capacity in the mammalian heart. Metabolic control has potential for developing effective CM proliferation strategies. We sought to determine whether lactate dehydrogenase A (LDHA) regulated CM proliferation by inducing metabolic reprogramming. Methods and results: LDHA expression was high in P1 hearts and significantly decreased during postnatal heart development. CM-specific LDHA knockout mice were generated using CRISPR/Cas9 technology. CM-specific LDHA knockout inhibited CM proliferation, leading to worse cardiac function and a lower survival rate in the neonatal apical resection model. In contrast, CM-specific overexpression of LDHA promoted CM proliferation and cardiac repair post-MI. The α-MHC-H2B-mCh/CAG-eGFP-anillin system was used to confirm the proliferative effect triggered by LDHA on P7 CMs and adult hearts. Metabolomics, proteomics and Co-IP experiments indicated that LDHA-mediated succinyl coenzyme A reduction inhibited succinylation-dependent ubiquitination of thioredoxin reductase 1 (Txnrd1), which alleviated ROS and thereby promoted CM proliferation. In addition, flow cytometry and western blotting showed that LDHA-driven lactate production created a beneficial cardiac regenerative microenvironment by inducing M2 macrophage polarization. Conclusions: LDHA-mediated metabolic reprogramming promoted CM proliferation by alleviating ROS and inducing M2 macrophage polarization, indicating that LDHA might be an effective target for promoting cardiac repair post-MI.

Understanding immune cell phenotypes in the tumor microenvironment (TME) is essential for explaining and predicting progression of non-small cell lung cancer (NSCLC) and its response to immunotherapy. Here we describe the single-cell transcriptomics of CD45+ immune cells from tumors, normal tissues and blood of NSCLC patients. We identified three clusters of immune cells exerting immunosuppressive effects: CD8+ T cells with exhausted phenotype, tumor-associated macrophages (TAMs) with a pro-inflammatory M2 phenotype, and regulatory B cells (B regs) with tumor-promoting characteristics. We identified genes that may be mediating T cell phenotypes, including the transcription factors ONECUT2 and ETV4 in exhausted CD8+ T cells, TIGIT and CTL4 high expression in regulatory T cells. Our results highlight the heterogeneity of CD45+ immune cells in the TME and provide testable hypotheses about the cell types and genes that define the TME.

To explore the relationship between kindergarten environmental factors, children's physical activity, and physical fitness, this study uses the stratified random sampling method to obtain 4,600 children in relevant kindergartens. The questionnaire survey and children's physical fitness test were completed with the help of parents and kindergarten staff. The exploratory (EFA) and confirmatory (CFA) factor analysis is used to process the obtained database and set the significance level of all indicators α = 0.05. The results show that kindergarten environmental factors significantly affect children's physical activity and healthy physical fitness. Children with large play areas in these kindergartens, more sports equipment items, who participate in more than three games per week, of no

Acetylation is an important and reversible post-translational modification (PTM) of protein, which is involved in many cellular physiological processes. In previous studies, lots of nutrient storage proteins were found to be highly acetylated in silkworms, and acetylation can improve the stability of these proteins. However, the related acetyltransferase was not involved. In the present work, a Bombyx mori nutrient storage protein, apolipophorin II (BmApoLp-II), was further confirmed to be acetylated, and the acetylation could improve its protein expression. Furthermore, RNAi and Co-IP showed that the acetyltransferase BmCBP was found to catalyze the acetylation modification of BmApoLp-II, and thus affect its protein expression. Meanwhile, it was proved that acetylation could improve the stability of the BmApoLp-II protein by completing its ubiquitination. These results lay a foundation for further study on the mechanism of regulating nutrition storage and hydrolysis utilization of storage proteins by BmCBP and the acetylation in the silkworm Bombyx mori.

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly (ADP-ribose) polymerase-1 (PARP1) and bromodomain containing protein 4 (BRD4), which had important cross relation in the global network of breast cancer, reflecting the synthetic lethal effect. A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragment-based combinatorial screening and activity assays that together led to the chemical optimization. Among these compounds, 19d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1, respectively. Compound 19d was further shown to efficiently modulate the expression of BRD4 and PARP1. Subsequently, compound 19d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase. Following pharmacokinetic studies, compound 19d showed its antitumor activity in breast cancer susceptibility gene 1/2 (BRCA1/2) wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight. These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.

We report a case of a 72-year-old female who developed bilateral pseudo-vitelliform dystrophy after taking desferrioxamine for the treatment of chronic iron overload. The patient then developed a right superior hemiretinal vein occlusion associated with intraretinal fluid in the right eye and was treated with monthly intravitreal aflibercept injections for 3 months followed by as required treatment. In addition to the intraretinal fluid responding to anti-VEGF treatment, there was a reduction in the size of the pseudo-vitelliform subfoveal deposit height, which was not seen in the untreated eye. Our case of an uncommon presentation of desferrioxamine-related maculopathy associated with a vein occlusion and the changes associated with intravitreal anti-VEGF treatment may help with the potential hypotheses of the pathophysiology of desferrioxamine-related pseudo-vitelliform retinal lesions and help with the potential future treatments of the condition.

Iron ion is widely present in the environment and in biological systems, and are indispensable trace elements in living organisms, so development of an efficient and simple sensor for sensing Fe(III) ions has attracted much attention. Here, six heterometallic AE-Ln coordination polymers (CPs) [Ln2 (pda)4(Hnda)2Ca2(H2O)2]·MeOH (Ln = Eu (1), Tb (2); H2pda = 2,6-pyridinedicarboxylic acid, H2nda = 2,3-naphthalenedicarboxylic acid), [Ln (pda)2 (nda)AE2(HCOO)(H2O)] (AE = Sr, Ln = Eu (3), Tb (4); AE = Ba, Ln = Eu (5), Tb (6)) with two-dimensional (2D) layer structures were synthesized by hydrothermal method. All of them were characterized by elemental analysis, XRD, IR, TG, as well as single crystal X-ray diffraction. They all show infinite 2D network structure, where complexes 1 and 2 are triclinic with space group of P1¯, while 3-6 belong to the monoclinic system, space group P21/n. The solid-state fluorescence lifetimes of complexes 1, 3 and 5 are τobs1 = 1930.94, 2049.48 and 2,413.04 µs, respectively, and the quantum yields Фtotal are 63.01, 60.61, 87.39%, respectively, which are higher than those of complexes 2, 4 and 6. Complexes 1-6 all exhibited efficient fluorescence quenching response to Fe3+ ions in water, and were not interfered by the following metal ions: Cu2+, Cd2+, Mg2+, Ni2+, Co2+, Ca2+, Ba2+, Sr2+, Li+, Na+, K+, Al3+, Fe2+, Pb2+, Cr3+, Mn2+ and Zn2+. The quenching coefficient KSV for complexes 1-6 is 1.41 × 105 M−1, 7.10 × 104 M−1, 1.70 × 105 M−1, 1.57 × 105 M−1, 9.37 × 104 M−1, 1.27 × 105 M−1, respectively. The fluorescence quenching mechanism of these complexes towards Fe3+ ions was also investigated. It is possible that the weak interaction formed between the complexes and the Fe3+ ions reduce the energy transfer from the ligand to the Ln3+ ion, producing the emission burst effect. This suggests that complexes 1-6 can be candidate for efficient luminescent sensor of Fe3+.

In this paper, a Divide-and-Cooperate Machine Learning Model (DCML) based Radial Basis Function Network (RBF) is constructed. This DCML is composed of several sub-RBF networks that take some variables as their inputs. The output of DCML is the sum of sub-RBF networks' outputs. The analysis of VC dimension of DCML shows in theory that its structural complexity is less than conventional Extended Radial Basis Function Network (ENRBF). The experimental results have verified that the DCML outperforms conventional ENRBF.

BackgroundChina has stepped into an era of aging society, where the impending considerable economic burden attributed to high prevalence of dementia in the elderly appears to be one of the most important health and social issues to deal with for the country. However, population-based quantification and projections for the economic burden of dementia in China are lacking for further health action and policy making.ObjectiveTo estimate and predict the costs of managing dementia in the elderly population aged 60 and above from 2010 to 2050 in China.MethodsData were collected from a six-province study (n = 7072) and other multiple sources for calculation of the economic burden of dementia. With the convincing data from published studies, we quantified and projected the costs attributed to dementia in China from 2010 to 2050.ResultsThe national cost of dementia in 2010 was estimated to be US$22.8 billion by the opportunity cost method and US$26.4 billion by the proxy method. In 2050, the costs would increase to US$372.3 billion by the opportunity cost method and US$430.6 billion by the proxy method, consuming 0.53% and 0.61% of China's total GDP, respectively. A series of sensitivity analyses showed that the changes in the proportions of informal caregiving led to the most robust changes in the total burden of care for dementia in China.ConclusionDementia represents an enormous burden on China's population health and economy. Due to the changes in policies and population structure, policymakers should give priority to dementia care.

The natural ecological conditions in the Shendong mining area in China are very fragile, and water resources are seriously lacking. As the production scale of the Shendong mine continues to expand, the demand for water for production and living is also increasing; however, the available surface and underground water is decreasing, and the water scarcity in the Shendong mine is becoming increasingly apparent. Obtaining water resources is a major technological challenge for green mining. The underground reservoir is a new type of underground water conservancy project, and the water shortage in China’s coal mine pits is resolved by underground reservoirs, which also makes a substantial contribution to the effective utilization of water resources. How the construction of underground reservoirs affects the groundwater system in a mining area has become one of the most important factors to consider when finding sites for underground reservoirs. In this study, we took the Daliuta Coal Mine as an example. A numerical model based on the hydrogeological conditions in the mining area was developed to determine the effects on groundwater using FEFLOW software via the finite element method. The model was used to analyze the impacts of coal seam mining thickness, overlying lithology, water-storage range and the water level of the underground reservoir on the groundwater flow system in the mining area. The results indicate that the thickness of the coal seam mining and the lithology of the overlying reservoir both had a significant effect on the upper aquifer system. The water-storage range and water level of the underground reservoirs were the main influences on the lower aquifer system. The results prove that underground reservoir storage had a good effect on water retention in the groundwater system in the mining area, and was able to achieve the desired result of storing groundwater and reducing water loss. It also had a positive feedback effect on the mining area’s environment.

Background: We previously found that loss of lncRNA-AZIN2 splice variant (AZIN2-sv) increases cardiomyocyte (CM) proliferation and attenuates adverse ventricular remodelling post-myocardial infarction (MI). However, whether inhibition of AZIN2-sv can simultaneously induce angiogenesis and thus improve prognosis after MI is unclear. Methods: We used in situ hybridization and quantitative PCR to determine AZIN2-sv expression in endothelial cells. Knockdown and overexpression were performed to detect the role of AZIN2-sv in endothelial cell function, angiogenesis and prognosis after MI. RNA pulldown, RNA immunoprecipitation and luciferase reporter assays were used to determine the interaction with talin1 (Tln1) protein and miRNA-214 (miR-214). DNA pulldown and chromatin immunoprecipitation (ChIP) assays were used to study AZIN2-sv binding to upstream transcription factors. Findings: AZIN2-sv was enriched in cardiac endothelial cells. The loss of AZIN2-sv reduced endothelial cell apoptosis and promoted endothelial sprouting and capillary network formation in vitro. Moreover, in vivo, the loss of AZIN2-sv induced angiogenesis and improved cardiac function after MI. Mechanistically, AZIN2-sv reduced Tln1 and integrin β1 (ITGB1) protein levels to inhibit neovascularization. AZIN2-sv activated the ubiquitination-dependent degradation of Tln1 mediated by proteasome 26S subunit ATPase 5 (PSMC5). In addition, AZIN2-sv could bind to miR-214 and suppress the phosphatase and tensin homologue (PTEN)/Akt pathway to inhibit angiogenesis. With regard to the upstream mechanism, Bach1, a negative regulator of angiogenesis, bound to the promoter of AZIN2-sv and increased its expression. Interpretation: Bach1-activated AZIN2-sv could participate in angiogenesis by promoting the PSMC5-mediated ubiquitination-dependent degradation of Tln1 and blocking the miR-214/PTEN/Akt pathway. Inhibition of AZIN2-sv induced angiogenesis and myocardial regeneration simultaneously, thus, AZIN2-sv could be an ideal therapeutic target for improving myocardial repair after MI. Fund: National Natural Science Foundations of China. Keywords: AZIN2-sv, Angiogenesis, Tln1, Ubiquitination

Objectives: To estimate the prevalence of anxiety, depression, and sleep problems among caregivers of persons living with neurocognitive disorders (PLWND) during the COVID-19 pandemic in China and investigate whether the COVID-19-related experiences were associated with the presence of anxiety, depression, and sleep problems.Methods: From March 1 to 31, 2020, 160 caregivers of PLWND participated in an online cross-sectional survey on the prevalence of anxiety, depression, and sleep problems. The 7-item Generalized Anxiety Disorder Scale (GAD-7) was administered to measure anxiety symptoms, and the 2-item Patient Health Questionnaire (PHQ-2) was used to assess depressive symptoms. Questions on sleep duration and sleep quality enquired about sleep problems. Six items were used to explore the COVID-19-related experiences, including community-level infection contact and the level of exposure to media information. We computed the prevalence rate of anxiety, depressive symptoms, and sleep problems. Univariate and multivariate logistic regression analyses were performed to investigate factors associated with these mental health problems.Results: The prevalence rate of anxiety, depression, and sleep problems were 46.9%, 36.3%, and 9.4%. Approximately 55 participants (34.4%) presented with two or more mental health problems. Women had a higher risk of developing anxiety symptoms (OR, 5.284; 95% CI, 2.068–13.503; p = 0.001). Having a mental disorder (OR, 5.104; 95% CI, 1.522–17.114; p = 0.008) was associated with an increased risk of depressive symptoms. Caregivers who preferred to access positive information (OR, 0.215; 95% CI, 0.058–0.793; p = 0.021) was associated with decreased risk of sleep problems.Conclusion: Anxiety and depressive symptoms were common among caregivers of older adults with dementia or mild cognitive impairment during the COVID-19 pandemic. Being female was an independent risk factor for experiencing anxiety symptoms. Preexisting mental disorders increased the risk of depressive symptoms among caregivers, while caregivers who prefer to access positive media information decreased sleep problems.

Depression is a widespread chronic medical illness affecting thoughts, mood, and physical health. However, the limited and delayed therapeutic efficacy of monoaminergic drugs has led to intensive research efforts to develop novel antidepressants. ARN-3236 is the first potent and selective inhibitor of salt-inducible kinase 2 (SIK2). In this study, a multidisciplinary approach was used to explore the antidepressant-like actions of ARN-3236 in mice. Chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, high performance liquid chromatography-tandem mass spectrometry, stereotactic infusion, viral-mediated gene transfer, western blotting, co-immunoprecipitation and immunofluorescence were used together. It was found that ARN-3236 could penetrate the blood-brain barrier. Repeated ARN-3236 administration induced significant antidepressant-like effects in both the CSDS and CUMS models of depression, accompanied with fully preventing the stress-enhanced SIK2 expression and cytoplasmic translocation of cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) in the hippocampus. ARN-3236 treatment also completely reversed the down-regulating effects of CSDS and CUMS on the hippocampal brain-derived neurotrophic factor (BDNF) system and neurogenesis. Moreover, we demonstrated that the hippocampal CRTC1-CREB-BDNF pathway mediated the antidepressant-like efficacy of ARN-3236. Collectively, ARN-3236 possesses strong protecting effects against chronic stress, and could be a novel antidepressant beyond monoaminergic drugs.

Myocardial fibrosis is well-known to be the aberrant deposition of extracellular matrix (ECM), which may cause cardiac dysfunction, morbidity, and death. Traditional Chinese medicine formula Si-Miao-Yong-An Decoction (SMYAD), which is used clinically in cardiovascular diseases has been recently reported to able to resist myocardial fibrosis. The anti-fibrosis effects of SMYAD have been evaluated; however, its intricate mechanisms remain to be clarified. Here, we found that SMYAD treatment reduced the fibrosis injury and collagen fiber deposition that could improve cardiac function in isoprenaline (ISO)-induced fibrosis rat models. Combined with our systematic RNA-seq data of SMYAD treatment, we demonstrated that the remarkable up-regulation or down-regulation of several genes were closely related to the functional enrichment of TGF-β and AMPK pathways that were involved in myocardial fibrosis. Accordingly, we further explored the molecular mechanisms of SMYAD were mainly caused by AMPK activation and thereby suppressing its downstream Akt/mTOR and TGF-β/SMAD3 pathways. Moreover, we showed that the ECM deposition and secretion process were attenuated, suggesting that the fibrosis pathological features are changed. Interestingly, we found the similar AMPK-driven pathways in NIH-3T3 mouse fibroblasts treated with ISO. Taken together, these results demonstrate that SMYAD may be a new candidate agent by regulating AMPK-driven Akt/mTOR and TGF-β/SMAD3 pathways for potential therapeutic implications of myocardial fibrosis.

Small molecule RNAs (microRNAs) are a kind of endogenous, stable, and noncoding RNA molecule that can regulate the expression of target genes such as DJ-1 at the posttranscriptional level. This study aimed to detect the expression of salivary microRNAs and to discover their value as a salivary potential biomarker for Parkinson’s disease (PD). Through a case-control study, RT-qPCR technology was used to detect the expression of miR-874 and miR-145-3p in the saliva of 30 PD patients and 30 healthy volunteers. Then we compared the differences in the expression levels of salivary miR-874 and miR-145-3p between the PD group and the control group and analyzed the correlation between the expression of salivary miR-874 and miR-145-3p in terms of age, gender, disease condition, and disease course. We found that salivary miR-874 and miR-145-3p were both positively expressed in the PD group and control group, and their expression in the PD group was higher than that in the control group. The expression of salivary miRNA-874 and miR-145-3p had no clear correlation to age, gender, total RNA concentrations in saliva, the score of UPDRSII, UPDRSIII, olfactory test scale, MMSE, MoCA, Hohn–Yahr stage and disease course. In conclusion, in the PD group and the control group with positive expression, the expression levels of miR-874 and miR-145-3p in the PD group were higher than those in the control group. The detection of miR-874 and miR-145-3p expression in saliva can be used as an auxiliary biomarker for PD.

Non-coding RNA, known as long non-coding RNA (lncRNA), circular RNA (circRNA) and microRNA (miRNA), are taking part in the multiple developmental processes in plants. However, the roles of which played during the cambium activity periodicity of woody plants remain poorly understood. Here, lncRNA/circRNA-miRNA-mRNA regulatory networks of the cambium activity periodicity in Populus tomentosa was constructed, combined with morphologic observation and transcriptome profiling. Light microscopy and Periodic Acid Schiff (PAS) staining revealed that cell walls were much thicker and number of cell layers was increased during the active-dormant stage, accompanied by abundant change of polysaccharides. The novel lncRNAs and circRNAs were investigated, and we found that 2037 lncRNAs and 299 circRNAs were differentially expression during the vascular cambium period, respectively. Moreover, 1046 genes were identified as a target gene of 2037 novel lncRNAs, and 89 of which were the miRNA precursors or targets. By aligning miRNA precursors to the 7655 lncRNAs, 21 lncRNAs were identified as precursors tof 19 known miRNAs. Furthermore, the target mRNA of lncRNA/circRNA-miRNA network mainly participated in phytohormone, cell wall alteration and chlorophyll metabolism were analyzed by GO enrichment and KEGG pathway. Especially, circRNA33 and circRNA190 taking part in the phytohormone signal pathway were down-regulated during the active-dormant transition. Xyloglucan endotransglucosylase/hydrolase protein 24-like and UDP-glycosyltransferase 85A1 involved in the cell wall modification were the targets of lncRNA MSTRG.11198.1 and MSTRG.1050.1. Notably, circRNA103 and MSTRG.10851.1 regulate the cambium periodicity may interact with the miR482. These results give a new light into activity–dormancy regulation, associated with transcriptional dynamics and non-coding RNA networks of potential targets identification.

Mindfulness is described as the non-judgmental awareness of experiences in the present moment. The sustained practice of mindfulness may also have beneficial effects on an individual’s well-being. For instance, mindfulness meditation is an effective approach for improving emotion regulation. Specifically, the early stage of mindfulness meditation training enhances emotional monitoring systems related to attention regulation and executive function. Reduced activity in the default mode network (DMN) would probably be observed corresponding to the attenuated mind wandering. In the present study, we hypothesized that alterations in functional activity in the frontal-parietal cortex and DMN may be induced by short-term mindfulness meditation. In this study, before and after 8 weeks of weekly Mindfulness-Based Stress Reduction (MBSR) training, healthy participants were evaluated using a mindfulness questionnaire and an affect schedule, as well as via resting-state functional magnetic resonance imaging. Sixteen right-handed non-meditators were enrolled. Another 16 demographically matched healthy adults without any meditation experience were recruited as controls. Pre- and post-MBSR assessments were compared. Increased regional homogeneity in the right superior parietal lobule and left postcentral gyrus (PoCG), as well as altered functional connectivity in PoCG-related networks, were observed post-MBSR. The mindfulness questionnaire scores also improved and negative affect was significantly decreased after MBSR. Together with reduced involvement of the posterior brain, our results suggest a tendency toward stronger involvement of the parietal cortex in mindfulness beginners. This study provides novel evidence regarding the optimization of emotional processing with short-term mindfulness meditation.

Bioconverting coal to methane is a green and environmental friendly method to reuse waste coal. In this study, heterologous bacteria were used for the gas-producing fermentation of lignite under laboratory conditions, simultaneously, different concentrations of ethanol added into the culture to investigate the effect of ethanol on gas production and microbial flora structure. Results show that when the ethanol concentration was 1%, the best methanogenesis was achieved at 44.86 mL/g, which was twice the gas production of 0% ethanol. Before and after gas fermentation, the composition and structure of the coal changed, the volatile matter and fixed carbon increased, and the ash decreased. The absorbance value at characteristic peaks of all functional groups decreased, new peaks were generated at 2,300/cm, and the peak value disappeared at 3,375/cm. Thus, microorganisms interacted with coal, consumed it, and produced new materials. The microbial flora changes during gas production were tracked in real time. 0.5 and 1% ethanol did not obviously change the bacterial communities but strongly influenced the archaeon communities, thereby changed the methane production pathway. In the absence of ethanol, Methanosarcina was continuously increasing with the extension of fermentation time, this pathway was the nutrient type of acetic acid. When ethanol was added, Methanobacterium gradually increased, the pathway was mainly hydrotropic type. In summary, adding ethanol can increase the coalbed methane production, change the structure and composition of coal, and facilitate the interaction of microbe with coal. Therefore, the methanogenic archaeon changes could help improve the methane-producing ability of lignite in the presence of ethanol.

ObjectiveSystematic Review was used to evaluate the efficacy and safety of Dalfampridine (DAP) in the treatment of Mobility Disability (MS) in patients with Multiple Sclerosis.MethodsClinical randomized controlled studies about DAP and placebo in the treatment of Mobility Disability in patients with Multiple Sclerosis until March 2019 were explored by searching Embase, PubMed, Cochrane, Web of Knowledge, and ClinicalTrials.gov. Literature screening, data extraction, quality assessment, and statistical analysis were performed by using Stata 14.0.Results10 papers were included in the meta-analysis, and the number of patients was 2100. In conclusion, the application of DAP in clinical can significantly improve the Mobility Disability of patients [OR = 2.73, 95%CI (1.66, 4.50), P10 mg) is a litter higher than the placebo control group.ConclusionDAP can effectively improve Mobility Disability in patients with Multiple Sclerosis, which is safe and reliable in specific DAP usage doses.

Background Antisense long noncoding RNAs (lncRNAs) are single‐stranded RNAs that overlapped gene‐coding regions on the opposite DNA strand and play as critical regulators in cardiovascular diseases. The high conservation and stability may be good advantages for antisense lncRNAs. However, the roles of antisense lncRNAs in cardiomyocyte proliferation and cardiac regeneration are still unknown. Methods and Results In this study, we found that Silent information regulator factor 2 related enzyme 1 (Sirt1) antisense lncRNA expression was significantly increased during heart development. By gain and loss function of Sirt1 antisense lncRNA using adenovirus and locked nucleic acid, respectively, we demonstrated that Sirt1 antisense lncRNA promoted cardiomyocyte proliferation in vitro and in vivo, and the suppression of Sirt1 antisense lncRNA inhibited cardiomyocyte proliferation. Moreover, overexpression of Sirt1 antisense lncRNA enhanced cardiomyocyte proliferation, attenuated cardiomyocyte apoptosis, improved cardiac function, and decreased mortality rate after myocardial infarction. Furthermore, Sirt1 antisense lncRNA can bind the Sirt1 3′‐untranslated region, enhancing the stability of Sirt1 and increasing Sirt1 abundance at both the mRNA and protein levels. Finally, we found that Sirt1 was involved in Sirt1 antisense lncRNA‐induced cardiomyocyte proliferation. Conclusions The present study identified Sirt1 antisense lncRNA as a novel regulator of cardiomyocyte proliferation and cardiac regeneration by interacting and stabilizing Sirt1 mRNA, which may serve as an effective gene target for preventing myocardial infarction.

In the title complex, [Cu(C7H7N2O2)2]·2CH3OH, the metal centre is coordinated by two 4-aminophenylhydroxamate bidentate ligands, in a distorted square-planar geometry. The asymmetric unit is completed by two methanol solvent molecules, which are involved in hydrogen bonding with N—H functionalities of the free hydroxamate groups. The crystal structure also features N—H...O bonds formed by the NH2 groups, and O—H...O hydrogen bonds with the methanol solvent molecules as donors.

In the title polymeric complex, {[CoSr(C7H3NO4)2(H2O)6]·2H2O}n, the CoII ion, which is situated on a crystallographic centre of inversion, is six-coordinated by two O atoms and two N atoms from two pyridine-2,4-dicarboxylate (pydc2−) ligands and two terminal water molecules in a slightly distorted octahedral geometry, to form a trans-[Co(pydc)2(H2O)2]2− unit. The SrII ion, situated on a C2 axis, is coordinated by four O atoms from four pydc2− ligands and four water molecules. The coordination geometry of the SrII atom can be best described as a distorted dodecahedron. Each SrII ion bridges four [Co(pydc)2(H2O)2]2− units by four COO− groups of four pydc2− ligands to form a three-dimensional network structure. Two additional solvent water molecules are observed in the crystal structure and are connected to the three-dimensional coordination polymer by O—H...O hydrogen bonds. Further intra- and intermolecular O—H...O hydrogen bonds consolidate the overall structure.

BackgroundEffects of beta-blockers on the prognosis of the heart failure patients with preserved ejection fraction (HFpEF) remain controversial. The aim of this meta-analysis was to determine the impact of beta-blockers on mortality and hospitalization in the patients with HFpEF.MethodsA search of MEDLINE, EMBASE, and the Cochrane Library databases from 2005 to June 2013 was conducted. Clinical studies reporting outcomes of mortality and/or hospitalization for patients with HFpEF (EF ≥ 40%), being assigned to beta-blockers treatment and non-beta-blockers control group were included.ResultsA total of 12 clinical studies (2 randomized controlled trials and 10 observational studies) involving 21,206 HFpEF patients were included for this meta-analysis. The pooled analysis demonstrated that beta-blocker exposure was associated with a 9% reduction in relative risk for all-cause mortality in patients with HFpEF (95% CI: 0.87 - 0.95; P < 0.001). Whereas, the all-cause hospitalization, HF hospitalization and composite outcomes (mortality and hospitalization) were not affected by this treatment (P=0.26, P=0.97, and P=0.88 respectively).ConclusionsThe beta-blockers treatment for the patients with HFpEF was associated with a lower risk of all-cause mortality, but not with a lower risk of hospitalization. These finding were mainly obtained from observational studies, and further investigations are needed to make an assertion.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been extensively demonstrated to benefit heart failure patients, but the role of underlying heart failure etiology in the outcomes was not consistently proven. This meta-analysis aimed to determine whether efficacy and effectiveness of CRT is affected by underlying heart failure etiology. METHODS AND RESULTS: Searches of MEDLINE, EMBASE and Cochrane databases were conducted to identify RCTs and observational studies that reported clinical and functional outcomes of CRT in ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) patients. Efficacy of CRT was assessed in 7 randomized controlled trials (RCTs) with 7072 patients and effectiveness of CRT was evaluated in 14 observational studies with 3463 patients In the pooled analysis of RCTs, we found that CRT decreased mortality or heart failure hospitalization by 29% in ICM patients (95% confidence interval [CI], 21% to 35%), and by 28% (95% CI, 18% to 37%) in NICM patients. No significant difference was observed between the 2 etiology groups (P = 0.55). In the pooled analysis of observational studies, however, we found that ICM patients had a 54% greater risk for mortality or HF hospitalization than NICM patients (relative risk: 1.54; 95% CI: 1.30-1.83; P

The SmIII ion in the title compound, [SmCl3(C12H10N2O)3], shows a coordination number of nine with a slightly distorted tricapped trigonal prismatic geometry based on a Cl3N6 donor set. The molecular structure is stabilized by three intramolecular O—H...Cl hydrogen bonds.

Marek's disease is a lymphoproliferative neoplastic disease of the chicken, which poses a serious threat to poultry health. Marek's disease virus (MDV)-induced T-cell lymphoma is also an excellent biomedical model for neoplasia research. Recently, miRNAs have been demonstrated to play crucial roles in mediating neoplastic transformation. To investigate host miRNA expression profiles in the tumor transformation phase of MDV infection, we performed deep sequencing in two MDV-infected samples (tumorous spleen and MD lymphoma from liver), and two non-infected controls (non-infected spleen and lymphocytes). In total, 187 and 16 known miRNAs were identified in chicken and MDV, respectively, and 17 novel chicken miRNAs were further confirmed by qPCR. We identified 28 down-regulated miRNAs and 11 up-regulated miRNAs in MDV-infected samples by bioinformatic analysis. Of nine further tested by qPCR, seven were verified. The gga-miR-181a, gga-miR-26a, gga-miR-221, gga-miR-222, gga-miR-199*, and gga-miR-140* were down-regulated, and gga-miR-146c was up-regulated in MDV-infected tumorous spleens and MD lymphomas. In addition, 189 putative target genes for seven differentially expressed miRNAs were predicted. The luciferase reporter gene assay showed interactions of gga-miR-181a with MYBL1, gga-miR-181a with IGF2BP3, and gga-miR-26a with EIF3A. Differential expression of miRNAs and the predicted targets strongly suggest that they contribute to MDV-induced lymphomagenesis.

The title compound {(C3H5N2)2[Pr2(C7H3NO4)4(H2O)4]}n, has a chain structure featuring a dimeric unit consisting of two PrIII atoms within a dodecahedral environment. Each of the metal cations is coordinated by two N atoms and two O atoms from two pyridine-2,5-dicarboxylate ligands, two O atoms from another two pyridine-2,5-dicarboxylate ligands and two water O atoms. The PrIII ions are bridged by two ligands along the c axis, forming the dimeric unit, and these are connected by four ligands along the b axis, forming a chain. N—H...O and O—H...O hydrogen bonds are found in the structure.

The asymmetric unit of the title compound, [CuCl(C12H8N2)2]·[CuCl2], contains two complex Cu(II) cations and two cuprate(I) anions. The Cu(II) atom is coordinated by two phenanthroline (phen) molecules and one chloride anion in a distorted trigonal–bipyramidal geometry. The Cu(II) complex cations form layers through π–π stacking [interplanar distance = 3.481 (2) Å]. The dichloridocuprate(I) anions are located between the layers, forming a sandwich-like structure.

Sex-specific traits that lead to the production of dimorphic gametes, sperm in males and eggs in females, are fundamental for sexual reproduction and accordingly widespread among animals. Yet the sex-biased genes that underlie these sex-specific traits are under strong selective pressure, and as a result of adaptive evolution they often become divergent. Indeed out of hundreds of male or female fertility genes identified in diverse organisms, only a very small number of them are implicated specifically in reproduction in more than one lineage. Few genes have exhibited a sex-biased, reproductive-specific requirement beyond a given phylum, raising the question of whether any sex-specific gametogenesis factors could be conserved and whether gametogenesis might have evolved multiple times. Here we describe a metazoan origin of a conserved human reproductive protein, BOULE, and its prevalence from primitive basal metazoans to chordates. We found that BOULE homologs are present in the genomes of representative species of each of the major lineages of metazoans and exhibit reproductive-specific expression in all species examined, with a preponderance of male-biased expression. Examination of Boule evolution within insect and mammalian lineages revealed little evidence for accelerated evolution, unlike most reproductive genes. Instead, purifying selection was the major force behind Boule evolution. Furthermore, loss of function of mammalian Boule resulted in male-specific infertility and a global arrest of sperm development remarkably similar to the phenotype in an insect boule mutation. This work demonstrates the conservation of a reproductive protein throughout eumetazoa, its predominant testis-biased expression in diverse bilaterian species, and conservation of a male gametogenic requirement in mice. This shows an ancient gametogenesis requirement for Boule among Bilateria and supports a model of a common origin of spermatogenesis.