MNMDCDA: prediction of circRNA-disease associations by learning mixed neighborhood information from multiple distances.

Emerging evidence suggests that circular RNA (circRNA) is an important regulator of a variety of pathological processes and serves as a promising biomarker for many complex human diseases. Nevertheless, there are relatively few known circRNA-disease associations, and uncovering new circRNA-disease associations by wet-lab methods is time consuming and costly. Considering the limitations of existing computational methods, we propose a novel approach named MNMDCDA, which combines high-order graph convolutional networks (high-order GCNs) and deep neural networks to infer associations between circRNAs and diseases. Firstly, we computed different biological attribute information of circRNA and disease separately and used them to construct multiple multi-source similarity networks. Then, we used the high-order GCN algorithm to learn feature embedding representations with high-order mixed neighborhood information of circRNA and disease from the constructed multi-source similarity networks, respectively. Finally, the deep neural network classifier was implemented to predict associations of circRNAs with diseases. The MNMDCDA model obtained AUC scores of 95.16%, 94.53%, 89.80% and 91.83% on four benchmark datasets, i.e., CircR2Disease, CircAtlas v2.0, Circ2Disease and CircRNADisease, respectively, using the 5-fold cross-validation approach. Furthermore, 25 of the top 30 circRNA-disease pairs with the best scores of MNMDCDA in the case study were validated by recent literature. Numerous experimental results indicate that MNMDCDA can be used as an effective computational tool to predict circRNA-disease associations and can provide the most promising candidates for biological experiments.

[Comparison of mouse models of depression induced by different modeling methods].

The present article was aimed to compare the effectiveness of different induction methods for depression models. Kunming mice were randomly divided into chronic unpredictable mild stress (CUMS) group, corticosterone (CORT) group, and CUMS+CORT (CC) group. The CUMS group received CUMS stimulation for 4 weeks, and the CORT group received subcutaneous injection of 20 mg/kg CORT into the groin every day for 3 weeks. The CC group received both CUMS stimulation and CORT administration. Each group was assigned a control group. After modeling, forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT) were used to detect the behavioral changes of mice, and the serum levels of brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) and CORT were detected with ELISA kits. Attenuated total refraction (ATR) spectra of mouse serum were collected and analyzed. HE staining was used to detect morphological changes in mouse brain tissue. The results showed that the weight of model mice from the CUMS and CC groups decreased significantly. There was no significant change in immobility time of model mice from the three groups in FST and TST, while the glucose preference of model mice from the CUMS and CC groups was significantly reduced (P < 0.05). The serum 5-HT levels of model mice from the CORT and CC groups were significantly reduced, while the serum BDNF and CORT levels of model mice from the CUMS, CORT, and CC groups showed no significant changes. Compared with their respective control groups, the three groups showed no significant difference in the one-dimensional spectrum of serum ATR. The difference spectrum analysis results of the first derivative of the spectrogram showed that the CORT group had the greatest difference from its respective control group, followed by the CUMS group. The structures of hippocampus in the model mice from the three groups were all destroyed. These results suggest that both CORT and CC treatments can successfully construct a depression model, and the CORT model is more effective than the CC model. Therefore, CORT induction can be used to establish a depression model in Kunming mice.

Robust and accurate prediction of self-interacting proteins from protein sequence information by exploiting weighted sparse representation based classifier.

BACKGROUND: Self-interacting proteins (SIPs), two or more copies of the protein that can interact with each other expressed by one gene, play a central role in the regulation of most living cells and cellular functions. Although numerous SIPs data can be provided by using high-throughput experimental techniques, there are still several shortcomings such as in time-consuming, costly, inefficient, and inherently high in false-positive rates, for the experimental identification of SIPs even nowadays. Therefore, it is more and more significant how to develop efficient and accurate automatic approaches as a supplement of experimental methods for assisting and accelerating the study of predicting SIPs from protein sequence information. RESULTS: In this paper, we present a novel framework, termed GLCM-WSRC (gray level co-occurrence matrix-weighted sparse representation based classification), for predicting SIPs automatically based on protein evolutionary information from protein primary sequences. More specifically, we firstly convert the protein sequence into Position Specific Scoring Matrix (PSSM) containing protein sequence evolutionary information, exploiting the Position Specific Iterated BLAST (PSI-BLAST) tool. Secondly, using an efficient feature extraction approach, i.e., GLCM, we extract abstract salient and invariant feature vectors from the PSSM, and then perform a pre-processing operation, the adaptive synthetic (ADASYN) technique, to balance the SIPs dataset to generate new feature vectors for classification. Finally, we employ an efficient and reliable WSRC model to identify SIPs according to the known information of self-interacting and non-interacting proteins. CONCLUSIONS: Extensive experimental results show that the proposed approach exhibits high prediction performance with 98.10% accuracy on the yeast dataset, and 91.51% accuracy on the human dataset, which further reveals that the proposed model could be a useful tool for large-scale self-interacting protein prediction and other bioinformatics tasks detection in the future.

Rare taxa maintain the stability of crop mycobiomes and ecosystem functions.

Plants harbour highly diverse mycobiomes which sustain essential functions for host health and productivity. However, ecological processes that govern the plant-mycobiome assembly, interactions and their impact on ecosystem functions remain poorly known. Here we characterized the ecological role and community assembly of both abundant and rare fungal taxa along the soil-plant continuums (rhizosphere, phyllosphere and endosphere) in the maize-wheat/barley rotation system under different fertilization practices at two contrasting sites. Our results indicate that mycobiome assembly is shaped predominantly by compartment niche and host species rather than by environmental factors. Moreover, crop-associated fungal communities are dominated by few abundant taxa mainly belonging to Sordariomycetes and Dothideomycetes, while the majority of diversity within mycobiomes are represented by rare taxa. For plant compartments, the abundant sub-community is mainly determined by stochastic processes. In contrast, the rare sub-community is more sensitive to host selection and mainly governed by deterministic processes. Furthermore, our results demonstrate that rare taxa play an important role in fungal co-occurrence network and ecosystem functioning like crop yield and soil enzyme activities. These results significantly advance our understanding of crop mycobiome assembly and highlight the key role of rare taxa in sustaining the stability of crop mycobiomes and ecosystem functions.

Host selection shapes crop microbiome assembly and network complexity.

Plant microbiomes are essential to host health and productivity but the ecological processes that govern crop microbiome assembly are not fully known. Here we examined bacterial communities across 684 samples from soils (rhizosphere and bulk soil) and multiple compartment niches (rhizoplane, root endosphere, phylloplane, and leaf endosphere) in maize (Zea mays)-wheat (Triticum aestivum)/barley (Hordeum vulgare) rotation system under different fertilization practices at two contrasting sites. Our results demonstrate that microbiome assembly along the soil-plant continuum is shaped predominantly by compartment niche and host species rather than by site or fertilization practice. From soils to epiphytes to endophytes, host selection pressure sequentially increased and bacterial diversity and network complexity consequently reduced, with the strongest host effect in leaf endosphere. Source tracking indicates that crop microbiome is mainly derived from soils and gradually enriched and filtered at different plant compartment niches. Moreover, crop microbiomes were dominated by a few dominant taxa (c. 0.5% of bacterial phylotypes), with bacilli identified as the important biomarker taxa for wheat and barley and Methylobacteriaceae for maize. Our work provides comprehensive empirical evidence on host selection, potential sources and enrichment processes for crop microbiome assembly, and has important implications for future crop management and manipulation of crop microbiome for sustainable agriculture.

Socioeconomic disparities and infancy growth trajectory: a population-based and longitudinal study.

BACKGROUND: The association of low socioeconomic status (SES) with childhood and adolescent obesity has been reported. It is unknown whether low SES affects body mass index (BMI) growth trajectory in the first 12 mo of life. Moreover, accelerated growth as a compensatory mechanism for low birth weight (LBW) during infancy, is an important predictor of later obesity. The aim of the present study was to examine the association of low SES with infancy BMI growth rate and trajectory for LBW and normal birth weight (NBW) infants. METHODS: From September 2012 to October 2014, a total of 387 infants in this longitudinal study was subjected to repeated measures of weight and length from birth to 12 mo in Hefei. Generalized growth mixture modeling was used to classify the infancy BMI growth trajectories. Differences in infancy BMI z score (zBMI) and BMI growth rate between low SES and high SES were estimated based on linear regression after adjusting for several confounders including maternal age, pregnancy BMI, physical activity during pregnancy, paternal BMI as well as alcohol use, paternal smoking status, breastfeeding duration and delivery mode. RESULTS: Infancy BMI trajectories in this study were classified into three categories: rapid growth (class 1), normal growth (class 2) and slow growth (class 3). Low SES infants had the higher zBMI than high SES infants for LBW group at age 6 mo [zBMI difference with 95% CI at 6 mo: 0.28(0.03, 0.53); at 12 mo: 0.21(0.01, 0.43)]. Low SES infants had more rapid zBMI growth rate than those with high SES for low birth weight between 0 and 6 months. Controlling for the confounders, these associations remained robust. We found the lower SES in the rapid growth group. CONCLUSIONS: These findings highlighted the impact of low SES on increasing BMI and accelerated growth during early infancy. Health care and relatively optimal family environment in the first 12 mo of life, especially for LBW infants, are benefit to shape the better infancy growth trajectory.

The STAT3 inhibitor WP1066 synergizes with vorinostat to induce apoptosis of mantle cell lymphoma cells.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t (11; 14) (q13; q32). Drug resistance remains a formidable obstacle to treatment and the median survival for MCL patients is between 3 and 5 years. Thus, there is an urgent need to discover novel approaches to MCL therapy. The signal transducer and activation of transcription 3 (STAT3) has been found to be constitutively activated in several subtypes of MCL cell lines and MCL tumors. WP1066, a small-molecule inhibitor of STAT3, exerted antitumor activity in hematological and solid malignancies by inhibiting key survival and growth signaling pathways. In the present study, we evaluated the antiproliferative and proapoptotic activity of WP1066 combined with pan-histone deacetylase (HDAC) inhibitor vorinostat (SAHA) in a panel of MCL cell lines. In addition, potential mechanisms involved were also explored. The outcome showed that combination of WP1066 with SAHA resulted in synergistic growth inhibition and apoptosis induction in MCL cell lines in vitro. Furthermore, combination of WP1066 with SAHA inhibited the constitutive STAT3 activation and modulated mRNA expressions of anti- and pro-apoptotic genes. Our findings suggest that agents targeting the STAT3 pathway such as WP1066 may be useful therapeutic drugs for MCL when combined with SAHA.

Rice black-streaked dwarf virus genome segment S5 is a bicistronic mRNA in infected plants.

Rice black-streaked dwarf virus (RBSDV) is a recognized member of the genus Fijivirus, family Reoviridae. Genome segment S5 has a putative second ORF partially overlapping the major ORF but in a different reading frame. This putative ORF is present in a published sequence and in two Chinese isolates now sequenced. Antibodies were raised against purified P5-1 and P5-2 fusion proteins expressed in a prokaryotic system. In western blots, these antibodies reacted with proteins of about 106 and 27 kDa, respectively, as predicted by sequence analysis. In immunoelectron microscopy, antibodies to P5-1 reacted with viroplasms, indicating that P5-1 is a component of viroplasms, but no labeling was observed with P5-2 antisera. Northern blot assays showed that the genome segment S5 was transcribed as a single mRNA with no subgenomic RNA. These results show that S5 is functionally bicistronic in infected plants. Possible translational mechanisms for P5-2 are discussed.

Kombo knife combined with sorafenib in liver cancer treatment: Efficacy and safety under immune function influence.

BACKGROUND: In the quest to manage hepatocellular carcinoma (HCC), the focus has shifted to a more holistic approach encompassing both data analytics and innovative treatments. Analyzing rich data resources, such as the cancer genome atlas (TCGA), and examining progressive therapies can potentially reshape the trajectory of HCC treatment. AIM: To elucidate the immunological genes and the underlying mechanism of the combined Kombo knife and sorafenib regimen for HCC by analyzing data from TCGA and machine learning data. METHODS: Immune attributes were evaluated via TCGA's postablation HCC RNA sequencing data. Using weighted gene coexpression network analysis and machine learning, we identified genes with high prognostic value. The therapeutic landscape and safety metrics of the integrated treatment were critically evaluated across cellular and animal models. RESULTS: Immune genes-specifically, peptidylprolyl isomerase A and solute carrier family 29 member 3-emerged as significant prognostic markers. Enhanced therapeutic outcomes, such as prolonged progression-free survival and an elevated overall response rate, characterize the combined approach, with peripheral blood mononuclear cells displaying potent effects on HCC dynamics. CONCLUSION: The combination of Kombo knife with sorafenib is an innovative HCC treatment modality anchored in immune-centric strategies.

Clinical features and demographic characteristics of gestational trophoblastic neoplasia: Single center experience and the SEER database.

The aim of this study was to analyze the clinical features and demographic characteristics of gestational trophoblastic neoplasia (GTN) patients, specifically choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumor (ETT). We utilized data from a local hospital and the SEER database, as well as survival outcomes of CC in SEER database. Additionally, we used multiple risk factors to create a prognostic nomogram model for CC patients. The study included GTN patients from the SEER database between 1975 and 2016 as well as those from the First Affiliated Hospital of Xi 'an Jiaotong University between January 2005 and May 2022. Related factors of patients were compared using the chi-square (χ2) or Fisher's exact test. For assessing overall survival we employed the Kaplan-Meier method and log-rank test. To construct the nomogram, we used Cox regression. Statistically significant differences were found between CC and PSTT/ETT patients in terms of surgery in local hospital, as well as age and year of diagnosis in the SEER database. Moreover, significant differences were observed between low and high (HR) /ultra-high risk (UHR) groups regarding FIGO stage, surgery and chief complaint at the local hospital, and FIGO stage, surgery and unemployment in the SEER database. The Cox regression analysis confirmed that age, race, surgery, marital status, FIGO stage, and unemployment were correlated with CC prognosis. Furthermore, the analysis showed that patients aged 40 years or older and those with FIGO Ⅲ/Ⅳ were independent prognostic factors of CC. The study indicates that atypical symptoms or signs may be the main reasons for HR /UHR patients to seek medical treatment. Therefore, providing multidisciplinary care is recommended for CC patients experiencing psychological distress due to unfavorable marital status or unemployment.

Microbial species pool-mediated diazotrophic community assembly in crop microbiomes during plant development.

Plant-associated diazotrophs strongly relate to plant nitrogen (N) supply and growth. However, our knowledge of diazotrophic community assembly and microbial N metabolism in plant microbiomes is largely limited. Here we examined the assembly and temporal dynamics of diazotrophic communities across multiple compartments (soils, epiphytic and endophytic niches of root and leaf, and grain) of three cereal crops (maize, wheat, and barley) and identified the potential N-cycling pathways in phylloplane microbiomes. Our results demonstrated that the microbial species pool, influenced by site-specific environmental factors (e.g., edaphic factors), had a stronger effect than host selection (i.e., plant species and developmental stage) in shaping diazotrophic communities across the soil-plant continuum. Crop diazotrophic communities were dominated by a few taxa (~0.7% of diazotrophic phylotypes) which were mainly affiliated with Methylobacterium, Azospirillum, Bradyrhizobium, and Rhizobium. Furthermore, eight dominant taxa belonging to Azospirillum and Methylobacterium were identified as keystone diazotrophic taxa for three crops and were potentially associated with microbial network stability and crop yields. Metagenomic binning recovered 58 metagenome-assembled genomes (MAGs) from the phylloplane, and the majority of them were identified as novel species (37 MAGs) and harbored genes potentially related to multiple N metabolism processes (e.g., nitrate reduction). Notably, for the first time, a high-quality MAG harboring genes involved in the complete denitrification process was recovered in the phylloplane and showed high identity to Pseudomonas mendocina. Overall, these findings significantly expand our understanding of ecological drivers of crop diazotrophs and provide new insights into the potential microbial N metabolism in the phyllosphere.IMPORTANCEPlants harbor diverse nitrogen-fixing microorganisms (i.e., diazotrophic communities) in both belowground and aboveground tissues, which play a vital role in plant nitrogen supply and growth promotion. Understanding the assembly and temporal dynamics of crop diazotrophic communities is a prerequisite for harnessing them to promote plant growth. In this study, we show that the site-specific microbial species pool largely shapes the structure of diazotrophic communities in the leaves and roots of three cereal crops. We further identify keystone diazotrophic taxa in crop microbiomes and characterize potential microbial N metabolism pathways in the phyllosphere, which provides essential information for developing microbiome-based tools in future sustainable agricultural production.

Interactions between the P6 and P5-1 proteins of southern rice black-streaked dwarf fijivirus in yeast and plant cells.

Southern rice black-streaked dwarf virus (SRBSDV) is a recently described member of the genus Fijivirus, family Reoviridae. The roles of the proteins encoded by the SRBSDV genome have rarely been studied. In a yeast two-hybrid (YTH) assay in which SRBSDV P6, a putatively multifunctional protein, was used as bait and an SRBSDV cDNA library was used as prey, there was a strong interaction between the P6 and P5-1 proteins. The interaction was confirmed by bimolecular fluorescence complement (BiFC) assay in plant cells. YTH analysis using truncated mutants showed that the N-terminal region (amino acids 9-231) of P5-1 is necessary for binding P5-1 to P6 and that the N-terminal fragment (amino acids 1-93) of P6 is necessary for its interaction with P5-1. SRBSDV P5-1 formed granules positioned at the cell periphery in Nicotiana benthamiana leaves; P6 was present in both the cytoplasm and the nucleus and formed punctate bodies associated with the cell periphery. Immunogold labeling showed that both P6 and P5-1 localized within viroplasms in infected cells of rice plants. These results suggest that the interaction between P5-1 and P6 of SRBSDV may be involved in the formation of viroplasms.

Correlation analysis of vaginal microecology and different types of human papillomavirus infection: a study conducted at a hospital in northwest China.

Background: Vaginal microecology has a definite influence on human papillomavirus (HPV) infection and clearance, but the specific correlation is still controversial. This research aimed to investigate the differences in the vaginal microenvironment of different types of HPV infection and also provide data supporting clinical diagnosis and treatment. Methods: According to strict inclusion and exclusion criteria, the case data of 2,358 female patients who underwent vaginal microecology and HPV-DNA tests at the same time in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Xi'an Jiaotong University from May 2021 to March 2022 were retrospectively analyzed. The population was divided into two groups: an HPV-positive group and an HPV-negative group. HPV-positive patients were further classified into HPV16/18-positive group and HPV other subtypes positive group. The vaginal microecology of HPV-infected patients was analyzed using the chi-square test, Fisher's exact test, and logistic regression. Results: Among the 2,358 female patients, the HPV infection rate was 20.27% (478/2,358), of which the HPV16/18 infection rate was 25.73% (123/478), and the HPV other subtypes infection rate was 74.27% (355/478). The difference in HPV infection rates between the age groups was statistically significant (P < 0.01). The prevalence of mixed vaginitis was 14.37% (339/2,358), with bacterial vaginosis (BV) paired with aerobic vaginitis (AV) accounting for the majority (66.37%). The difference in HPV infection rates among mixed vaginitis was not statistically significant (P > 0.05). The prevalence of single vaginitis was 24.22% (571/2,358), with the most frequent being vulvovaginal Candidiasis (VVC; 47.29%, 270/571), and there was a significant difference in HPV infection rates among single vaginitis (P < 0.001). Patients with BV had a higher risk of being positive for HPV16/18 (OR: 1.815, 95% CI: 1.050-3.139) and other subtypes (OR: 1.830, 95% CI: 1.254-2.669). Patients with Trichomoniasis were at higher odds of other HPV subtype infections (OR: 1.857, 95% CI: 1.004-3.437). On the contrary, patients with VVC had lower odds of becoming infected with other HPV subtypes (OR: 0.562, 95% CI: 0.380-0.831). Conclusion: There were disparities in HPV infection among different age groups; therefore, we should pay attention to the prevention and treatment of susceptible individuals. BV and Trichomoniasis are linked to HPV infection; hence, restoring the balance of vaginal microecology could assist in the prevention of HPV infection. As a protective factor for other HPV subtype infections, VVC may provide new insights into the development of immunotherapeutic therapies.

Current Status and Influencing Factors of Readiness for Discharge of Elderly Patients with Chronic Obstructive Pulmonary Disease.

Objective: Readiness for hospital discharge is an important indicator of patients' transition from illness to health and can predict rehabilitation and prognosis. Identifying factors that influence readiness for discharge is crucial for developing effective nursing interventions. Therefore, this study aims to investigate the current status of discharge readiness and its influencing factors in elderly patients with chronic obstructive pulmonary disease (COPD). Methods: A total of 311 elderly inpatients diagnosed with COPD were enrolled in this investigation at a tertiary hospital in Chengdu between December 2021 and June 2022. Questionnaires were designed to collect general information, disease-related information, and responses to the Readiness for Hospital Discharge Scale (RHDS) and the Quality of Discharge Teaching Scale (QDTS). Univariate and multivariate linear regression analyses were employed to further analyze factors related to discharge readiness and the correlation between discharge readiness and the quality of discharge guidance. Results: The total score of discharge readiness of elderly COPD patients was 77.72 ± 11.86 with a mean score of 6.48 ± 0.19 for each item. The quality of discharge instructions was 110.54 ± 15.66, with a mean score of 6.12 ± 0.15 for each item. Discharge preparation was positively correlated with the quality of discharge guidance. Multivariate analysis showed that marital status, admission mode, length of stay in hospital, Classification of Severity of Airflow Limitation, mMRC classification, number of medications taken with discharge, presence of inhalers in medication orders, mode of home oxygen therapy, and quality of discharge guidance were independent factors of discharge readiness in elderly COPD patients (P < 0.05). Conclusion: Both discharge readiness and the quality of discharge guidance for elderly COPD patients in China are currently suboptimal and need further improvement. The survey findings provide valuable insights that can guide future management practices and interventions aimed at improving discharge readiness.

Wnt/ß-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells.

BACKGROUND: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. METHODS: ATRA content was detected with ELISA and HPLC-MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro-computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. RESULTS: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/ß-catenin, and reduced by inhibiting this pathway. ß-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. CONCLUSIONS: Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

Naoluo Xintong Decoction Ameliorates Cerebral Ischemia-Reperfusion Injury by Promoting Angiogenesis through Activating the HIF-1α/VEGF Signaling Pathway in Rats.

Background: Naoluo Xintong decoction (NLXTD) is a traditional Chinese medicine (TCM) formula which has been used to improve neuronal functional recovery after cerebral ischemic stroke. However, the molecular mechanism underlying NLXTD's amelioration of ischemic stroke remains unclear. The present study was designed to explore the effect and mechanism of NLXTD on brain angiogenesis in a rat model with cerebral ischemia-reperfusion (I/R) injury targeting the hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway. Materials and Methods: Cerebral I/R model was established by the classical middle cerebral artery occlusion (MCAO) method. Sprague-Dawley (SD) male rats (n = 80) were randomly divided into the sham-operation group, the model group, the HIF-1α inhibitor 2-methoxyestradiol (2ME2) group, the 2ME2 with NLXTD group, and the NLXTD group. Neurological deficit test, TTC staining, H&E staining, TUNEL staining, immunohistochemistry (IH), immunofluorescence (IF), western blot, and quantitative RT-PCR were performed to evaluate the effect of NLXTD after MCAO. Results: Administration of NLXTD significantly decreased neuron deficiency scores, reduced brain infarct volume, and lowered damaged and apoptotic cells after brain I/R injury in rats. Meanwhile, NLXTD had a protective effect on angiogenesis by increasing the MVD and the expressions of BrdU and CD34, which enhanced the number of endothelial cells in the ischemic penumbra brain. NLXTD treatment significantly raised the protein and mRNA levels of HIF-1α, VEGF, VEGFR2, and Notch1 compared with the model treatment. In contrast, a specific HIF-1α inhibitor, 2ME2, inhibited the improvement of neurological function and angiogenesis in NLXTD-induced rats with cerebral I/R injury, suggesting that NLXTD played a positive role in ischemic brain injury by activating the HIF-1α/VEGF signaling pathway. Conclusions: NLXTD exerts neuroprotection targeting angiogenesis by upregulating the HIF-1α/VEGF signaling pathway on cerebral I/R injury rats.

Synergistic effects of CP-25 and 5-fluorouracil on the hepatocellular carcinoma in vivo and in vitro through regulating activating mitochondrial pathway.

Paeoniflorin-6'-O-benzene sulfonate (CP-25) has therapeutic potential for the treatment of hepatocellular carcinoma (HCC). 5-Fluorouracil (5-Fu) has been a conventional chemotherapeutic agent for HCC. Unfortunately, the nonspecific cytotoxicity and multidrug resistance caused by long-term use limited the clinical efficacy of 5-Fu. This study was aimed to investigate whether the combination of CP-25 and 5-Fu could generate synergistic effect in inhibiting HCC. The experiments on the diethylnitrosamine (DEN) -induced mice showed that compared with applying single drugs, the combination of CP-25 and 5-Fu presented stronger inhibition in tumor nodule and volume. Meanwhile, CP-25 and 5-Fu activated the intrinsic mitochondrial apoptosis pathway induced by P53, inhibited anti-apoptotic B-cell lymphoma (Bcl-2), induced the pro-apoptotic Bcl-2-associated X protein (Bax), Cytochrome-C and caspases. In addition, the synergistic effect was also validated in Bel-7402 and HepG-2 cells in vitro. This research not only provides a novel and effective combination strategy for the therapy of HCC but also provides an experimental basis for the development of CP-25 and 5-Fu compound preparation.

Associations of cord blood meta-inflammation and vitamin D with neurodevelopmental delay: A prospective birth cohort study in China.

Aim: To estimate the associations of cord meta-inflammatory markers with neurodevelopment, including the potential impact of cord blood vitamin D levels. Method: The prospective cohort study comprised 7198 participants based on the Maternal & Infants Health in Hefei study. Cord blood C-peptide, high-sensitive C-reactive protein (hsCRP), high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, triglycerides and 25(OH)D levels were measured. The Gesell Developmental Schedules were used to assess neurodevelopmental outcomes in offspring. Results: After adjusting potential confounders, per quartile increase in cord blood 25(OH)D concentrations was associated with a decreased risk of neurodevelopmental delay [hazard ratios (HR) 0.65 (95% CI 0.57, 0.74)]. Conversely, significant positive associations with cord blood serum C-peptide levels above the 90th percentile [HR 2.38 (95% CI 1.81, 3.13)] and higher levels of cord hsCRP (per quartile increase) [HR 1.18 (95% CI 1.01, 1.37)] with neurodevelopmental delay were observed. These associations could vary by quartiles of cord blood 25(OH)D levels: the adjusted HRs in neurodevelopmental delay comparing children with vs without hyperinsulinemia were 1.28 (95% CI: 1.03, 1.59) for quartiles 1 (lowest), and 1.06 (95% CI: 0.78, 1.44) for quartile 4 (highest). Conclusions: Immune activation and metabolic abnormalities in fetal circulation were associated with neurodevelopmental delay in offspring, which could be attenuated by higher cord blood 25(OH)D levels in a dose-response manner.

[Characteristics of acidification and the distribution of available phosphorus along soil depths in heavy clay soils in southern Henan Province, China]. / è±«å—é»æ¿åœŸå£¤åˆ†å±‚é ¸åŒ–å’Œè€•å±‚é€Ÿæ•ˆç£·åˆ†å¸ƒç‰¹å¾.

The acidification of agricultural soil in the southern part of the North China Plain has become more obvious, which is particularly true for the heavy clay soil types, such as yellow-cinnamon and lime concretion black soils. To understand the spatial variability of the pH value and nutrients on the vertical agricultural soil profile of heavy clay soils in this area, we measured pH values and available phosphorus (AP) in 63 farmland sample points from Xiping County in the southern Henan Province. Geostatistical methods and ArcGIS technology were used to map soil pH values along three soil depths (0-10, 10-20, and 20-30 cm) and the spatial distribution of soil AP in the tillage layer (0-20 cm). Furthermore, the correlation between pH and AP was analyzed. The results showed that mean pH values of typical yellow-cinnamon and typical fluvo-aquic soils from three soil layers were 4.98, 4.93, 5.31, and 5.46, 5.81, 6.26, respectively, which gradually increased with soil depths. However, there was no significant difference among the three soil layers. Mean pH values of typical lime concretion black soil from the three soil layers were 5.23, 5.43 and 6.03, respectively, and that of the 20-30 cm soil layer was significantly higher than that of the 0-10 cm (by 0.8-1 pH unit) and the 10-20 cm layers. The pH of the 20-30 cm soil layer of the calcareous lime concretion black and moist soils were also significantly higher than that of the 0-10 and 10-20 cm soil layers. The AP contents of the typical yellow-cinnamon, typical lime concretion black, moist, typical fluvo-aquic and calcareous lime concretion black soils in 0-20 cm soil layer were 8.85-54.75, 4.27-37.49, 8.22-51.80, 6.07-34.82, and 13.22-22.85 mg·kg-1, respectively. The results of the map indicated that the areas with low AP were distributed in the middle of the study area in blocks, and the areas with high AP were distributed around the study area in dots and flakes. The pH values of the typical yellow-cinnamon, typical lime concretion black, and moist soils positively correlated with the content of AP in the 0-20 cm soil layer. In conclusion, the heavy clay soil in southern Henan Province became stratified acidification, which slowed down along the soil depth. Soil AP contents in the tillage layer were distributed unevenly in the study area, and were affected by soil types and soil pH. These results would be useful for the improvement of heavy clay soil acidification in the southern part of the North China Plain.

IL-9 contributes to immunosuppression mediated by regulatory T cells and mast cells in B-cell non-hodgkin's lymphoma.

It has been known that regulatory T (Treg) cells and mast cells (MCs) are involved in tumor immunity regulation, but the exact roles and mechanisms of Treg cells and MCs in B-cell non-Hodgkin's lymphoma (NHL) are incompletely defined. In the present study, we found that the number of Foxp3(+) Treg cells and CD117(+) MCs increased in B-cell NHL patients. Concomitantly, a high level of interleukin (IL)-9 was observed in the sera from B-cell NHL patients. Neutralizing IL-9 significantly inhibited tumor growth in the lymphoma model of murine, and this process was associated with down-regulation of Treg cells and MCs. Furthermore, IL-9 was also demonstrated to induce expression of MC-related genes and proliferation of MCs from the bone marrow stem cells. Collectively, our results indicate that Treg cell and MCs are involved in immunosuppression in B-cell NHL, and IL-9 is a key mediator of Treg cells and MCs in that process. These findings provide novel insight for the pathogenesis and possible therapeutic strategy of B-cell NHL.