Principled Multilayer Network Embedding

Multilayer network analysis has become a vital tool for understanding different relationships and their interactions in a complex system, where each layer in a multilayer network depicts the topological structure of a group of nodes corresponding to a particular relationship. The interactions among different layers imply how the interplay of different relations on the topology of each layer. For a single-layer network, network embedding methods have been proposed to project the nodes in a network into a continuous vector space with a relatively small number of dimensions, where the space embeds the social representations among nodes. These algorithms have been proved to have a better performance on a variety of regular graph analysis tasks, such as link prediction, or multi-label classification. In this paper, by extending a standard graph mining into multilayer network, we have proposed three methods ("network aggregation," "results aggregation" and "layer co-analysis") to project a multilayer network into a continuous vector space. From the evaluation, we have proved that comparing with regular link prediction methods, "layer co-analysis" achieved the best performance on most of the datasets, while "network aggregation" and "results aggregation" also have better performance than regular link prediction methods

MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells

MicroRNA-140-5p (miR-140-5p) plays a pivotal role in human cancers. However, its role and molecular mechanisms in breast carcinoma are not fully explored. Using miR-140-5p transfected breast cancer cell line MDA-MB-231, several in vitro experiments were performed and described in this paper. They consist of the cell proliferation assay, wound healing assay, transwell assay, colony formation assays and qRTPCR. Expression levels of target proteins were determined using western blotting. In addition, experiments on animal models were performed to study the possible role of miR-140-5p in tumorigenesis of breast carcinoma cells. The induction of experimental breast tumor in mice model was achieved through the incorporation of MDA-MB-231 tumor cells subcutaneously into the middle left side of the mice. The results showed that miR-140-5p up-regulation significantly suppresses proliferation, cellular invasion and migration of breast carcinoma cells. Furthermore, miR-140-5p up-regulation stops breast cancer cells at G0/G1 phase. The results of the animal model indicated that up-regulation of miR-140-5p suppresses its tumorigenic ability. Moreover, we also found that miR-140-5p up-regulation reduces the phosphorylation level of STAT3, p65, and AKT. In addition, miR-140-5p overexpression significantly decreases CDK2 expression while increasing E-cadherin expression level. These data revealed that miR-140-5p suppressed tumor progression of breast carcinoma cells through inhibition of the AKT/STAT3/NF-κB pathway. Taken the present study results together, we can conclude that miR-140-5p may act as a novel target in microRNA-targeting anticancer strategy for the treatment of breast cancer

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

Potential roles of non-lymphocytic cells in the pathogenesis of IgG4-related disease

Studies have confirmed the involvement of a variety of lymphocyte subsets, including type 2 helper T lymphocytes (Th2) and IgG4+ B lymphocytes, in the pathogenesis of IgG4-related disease (IgG4-RD). Those lymphocytes contribute to the major pathogenetic features of IgG4-RD. However, they are not the only cellular components in the immunoinflammatory environment of this mysterious disease entity. Recent studies have suggested that various non-lymphocytic components, including macrophages and fibroblasts, may also play an important role in the pathogenetic process of IgG4-RD in terms of contributing to the chronic and complex progress of the disease. Therefore, the potential role of non-lymphocyte in the pathogenesis of IgG4-RD is worth discussing

Increased Expression of Ganglioside GM1 in Peripheral CD4+ T Cells Correlates Soluble Form of CD30 in Systemic Lupus Erythematosus Patients

Gangliosides GM1 is a good marker of membrane microdomains (lipid rafts) with important function in cellular activation processes. In this study we found that GM1 expression on CD4+ T cells and memory T cells (CD45RO/CD4) were dramatic increased after stimulation with phytohaemagglutinin in vitro. Next, we examined the GM1 expression on peripheral blood CD4+ T cells and CD8+ T cells from 44 patients with SLE and 28 healthy controls by flow cytometry. GM1 expression was further analyzed with serum soluble CD30 (sCD30), IL-10, TNF-alpha and clinical parameters. The mean fluorescence intensity of GM1 on CD4+ T cells from patients with SLE was significantly higher than those from healthy controls, but not on CD8+ T cells. Increased expression of GM1 was more marked on CD4+/CD45RO+ memory T cells from active SLE patients. Patients with SLE showed significantly elevated serum sCD30 and IL-10, but not TNF-alpha levels. In addition, we found that enhanced GM1 expression on CD4+ T cells from patients with SLE positively correlated with high serum levels of sCD30 and IgG as well as disease activity (SLEDAI scores). Our data suggested the potential role of aberrant lipid raft/GM1 on CD4+ T cells and sCD30 in the pathogenesis of SLE

GnRHa/Stanozolol Combined Therapy Maintains Normal Bone Growth in Central Precocious Puberty

BackgroundGonadotropin-releasing hormone agonist (GnRHa) is the gold standard in the treatment of Central Precocious Puberty (CPP) with progressive puberty and accelerative growth. However, GnRHa treatment is reported to result in growth deceleration and prevents growth plate development which leads to a reduction in height velocity. Stanozolol (ST) has been used to stimulate growth in patients with delayed growth and puberty, nevertheless, the effects and mechanisms of ST on CPP with GnRHa treatment are currently unclear.Methods and ResultsIn the current study, we recorded the following vital observations that provided insights into ST induced chondrogenic differentiation and the maintenance of normal growth plate development: (1) ST efficiently prevented growth deceleration and maintained normal growth plate development in rats undergoing GnRHa treatment; (2) ST suppressed the inhibitory effect of GnRHa to promote chondrogenic differentiation; (3) ST induced chondrogenic differentiation through the activation of the JNK/c-Jun/Sox9 signaling pathway; (4) ST promoted chondrogenic differentiation and growth plate development through the JNK/Sox9 signaling pathway in vivo.ConclusionsST mitigated the inhibitory effects of GnRHa and promoted growth plate development in rats. ST induced the differentiation of chondrocytes and maintained normal growth plate development through the activation of JNK/c-Jun/Sox9 signaling. These novel findings indicated that ST could be a potential agent for maintaining normal bone growth in cases of CPP undergoing GnRHa treatment

Application of family-centered empowerment model in primary caregivers of premature infants: A quasi-experimental study

ObjectiveTo explore the effect of the family-centered empowerment model (FECM) on reducing anxiety, improving care ability, and readiness for hospital discharge of main caregivers of preterm infants.MethodsThe primary caregivers of preterm infants who were admitted to the Neonatal intensive care Unit (NICU) of our center from September 2021 to April 2022 were selected as the research objects. According to the wishes of the primary caregivers of preterm infants, they were divided into group A (FECM group) and group B (non-FECM group). The intervention effects were evaluated with the Anxiety Screening Scale (GAD-7), the Readiness for Hospital Discharge Scale-Parent Version (RHDS-Parent Form), and the Primary Caregivers of Premature Infants Assessment of Care Ability Questionnaire.ResultsBefore the intervention, there was no statistically significant difference in the general information, anxiety screening, the scores of each dimension, and total score of the comprehensive ability of the main caregivers, and the score of caregiver preparedness between the two groups (P > 0.05). After the intervention, there were statistically significant differences in the anxiety screening, the total score and total score of each dimension of the care ability, and the score of caregiver preparedness between the two groups (P < 0.05).ConclusionsFECM can effectively reduce the anxiety of primary caregivers of premature infants and improve their readiness for hospital discharge and care ability. To improve the quality of life of premature infants by implementing personalized training, care guidance, and peer support

The role of high mobility group box chromosomal protein 1 in rheumatoid arthritis

Abstract High mobility group box chromosomal protein 1 (HMGB1) is a ubiquitous highly conserved single polypeptide in all mammal eukaryotic cells. HMGB1 exists mainly within the nucleus and acts as a DNA chaperone. When passively released from necrotic cells or actively secreted into the extracellular milieu in response to appropriate signal stimulation, HMGB1 binds to related cell signal transduction receptors, such as RAGE, TLR2, TLR4 and TLR9, and becomes a proinflammatory cytokine that participates in the development and progression of many diseases, such as arthritis, acute lung injury, graft rejection immune response, ischaemia reperfusion injury and autoimmune liver damage. Only a small amount of HMGB1 release occurs during apoptosis, which undergoes oxidative modification on Cys106 and delivers tolerogenic signals to suppress immune activity. This review focuses on the important role of HMGB1 in the pathogenesis of RA, mainly manifested as the aberrant expression of HMGB1 in the serum, SF and synovial tissues; overexpression of signal transduction receptors; abnormal regulation of osteoclastogenesis and bone remodelling leading to the destruction of cartilage and bones. Intervention with HMGB1 may ameliorate the pathogenic conditions and attenuate disease progression of RA. Therefore administration of an HMGB1 inhibitor may represent a promising clinical approach for the treatment of RA

Age at menarche and risk of major cardiovascular diseases: Evidence of birth cohort effects from a prospective study of 300,000 Chinese women

AbstractBackgroundPrevious studies of mostly Western women have reported inconsistent findings on the association between age at menarche and risk of cardiovascular disease (CVD). Little is known about the association in China where there has been a large intergenerational decrease in women's mean age at menarche.MethodsThe China Kadoorie Biobank recruited 302,632 women aged 30–79 (mean 50.5)years in 2004–8 from 10 diverse regional sites across China. During 7years follow-up, 14,111 incident cases of stroke, 14,093 of coronary heart disease (CHD), and 3200 CVD deaths were reported among 281,491 women who had no prior history of CVD at baseline. Cox regression yielded adjusted hazard ratios (HRs) relating age at menarche to CVD risks.ResultsThe mean (SD) age of menarche was 15.4 (1.9)years, decreasing from 16.2 (2.0) among women born before 1940 to 14.7 (1.6) for those born during the 1960s–1970s. The patterns of association between age at menarche and CVD risk appeared to differ between different birth cohorts, with null associations in older generations but U-shaped or weak positive associations in younger women, especially those born after the 1960s. After minimizing the potential confounding effects from major CVD risk factors, both early and late menarche, compared with menarche at age 13years, were associated with increased risk of CVD morbidity and mortality, which was more pronounced in younger generations.ConclusionAmong Chinese women the associations between age at menarche and risk of CVD differed by birth cohort, suggesting other factors may underpin the association

International Benchmarking of the Individual Tree Detection Methods for Modeling 3-D Canopy Structure for Silviculture and Forest Ecology Using Airborne Laser Scanning

Canopy structure plays an essential role in biophysical activities in forest environments. However, quantitative descriptions of a 3-D canopy structure are extremely difficult because of the complexity and heterogeneity of forest systems. Airborne laser scanning (ALS) provides an opportunity to automatically measure a 3-D canopy structure in large areas. Compared with other point cloud technologies such as the image-based Structure from Motion, the power of ALS lies in its ability to penetrate canopies and depict subordinate trees. However, such capabilities have been poorly explored so far. In this paper, the potential of ALS-based approaches in depicting a 3-D canopy structure is explored in detail through an international benchmarking of five recently developed ALS-based individual tree detection (ITD) methods. For the first time, the results of the ITD methods are evaluated for each of four crown classes, i.e., dominant, codominant, intermediate, and suppressed trees, which provides insight toward understanding the current status of depicting a 3-D canopy structure using ITD methods, particularly with respect to their performances, potential, and challenges. This benchmarking study revealed that the canopy structure plays a considerable role in the detection accuracy of ITD methods, and its influence is even greater than that of the tree species as well as the species composition in a stand. The study also reveals the importance of utilizing the point cloud data for the detection of intermediate and suppressed trees. Different from what has been reported in previous studies, point density was found to be a highly influential factor in the performance of the methods that use point cloud data. Greater efforts should be invested in the point-based or hybrid ITD approaches to model the 3-D canopy structure and to further explore the potential of high-density and multiwavelengths ALS data