Relation-Aware Neighborhood Matching Model for Entity Alignment

Entity alignment which aims at linking entities with the same meaning from different knowledge graphs (KGs) is a vital step for knowledge fusion. Existing research focused on learning embeddings of entities by utilizing structural information of KGs for entity alignment. These methods can aggregate information from neighboring nodes but may also bring noise from neighbors. Most recently, several researchers attempted to compare neighboring nodes in pairs to enhance the entity alignment. However, they ignored the relations between entities which are also important for neighborhood matching. In addition, existing methods paid less attention to the positive interactions between the entity alignment and the relation alignment. To deal with these issues, we propose a novel Relation-aware Neighborhood Matching model named RNM for entity alignment. Specifically, we propose to utilize the neighborhood matching to enhance the entity alignment. Besides comparing neighbor nodes when matching neighborhood, we also try to explore useful information from the connected relations. Moreover, an iterative framework is designed to leverage the positive interactions between the entity alignment and the relation alignment in a semi-supervised manner. Experimental results on three real-world datasets demonstrate that the proposed model RNM performs better than state-of-the-art methods

Table_1_Divergent molecular events underlying initial T-cell commitment in human prenatal and postnatal thymus.docx

IntroductionIntrathymic T-cell development is a coordinated process accompanied by dynamic changes in gene expression. Although the transcriptome characteristics of developing T cells in both human fetal and postnatal thymus at single-cell resolution have been revealed recently, the differences between human prenatal and postnatal thymocytes regarding the ontogeny and early events of T-cell development still remain obscure. Moreover, the transcriptional heterogeneity and posttranscriptional gene expression regulation such as alternative polyadenylation at different stages are also unknown.MethodIn this study, we performed integrative single-cell analyses of thymocytes at distinct developmental stages.ResultsThe subsets of prenatal CD4–CD8– double-negative (DN) cells, the most immature thymocytes responsible for T-cell lineage commitment, were characterized. By comprehensively comparing prenatal and postnatal DN cells, we revealed significant differences in some key gene expressions. Specifically, prenatal DN subpopulations exhibited distinct biological processes and markedly activated several metabolic programs that may be coordinated to meet the required bioenergetic demands. Although showing similar gene expression patterns along the developmental path, prenatal and postnatal thymocytes were remarkably varied regarding the expression dynamics of some pivotal genes for cell cycle, metabolism, signaling pathway, thymus homing, and T-cell commitment. Finally, we quantified the transcriptome-wide changes in alternative polyadenylation across T-cell development and found diverse preferences of polyadenylation site usage in divergent populations along the T-cell commitment trajectory.DiscussionIn summary, our results revealed transcriptional heterogeneity and a dynamic landscape of alternative polyadenylation during T-cell development in both human prenatal and postnatal thymus, providing a comprehensive resource for understanding T lymphopoiesis in human thymus.</p

Risk factors and mortality for elderly patients with bloodstream infection of carbapenem resistance Klebsiella pneumoniae: a 10-year longitudinal study

Abstract Background Bloodstream infection (BSI) caused by carbapenem resistant Klebsiella pneumoniae (CRKP), especially in elderly patients, results in higher morbidity and mortality. The purpose of this study was to assess risk factors associated with CRKP BSI and short-term mortality among elderly patients in China. Methods In this retrospective cohort study, we enrolled 252 inpatients aged ≥ 65 years with BSI caused by KP from January 2011 to December 2020 in China. Data regarding demographic, microbiological characteristics, and clinical outcome were collected. Result Among the 252 BSI patients, there were 29 patients (11.5%) caused by CRKP and 223 patients (88.5%) by carbapenem-susceptible KP (CSKP). The overall 28-day mortality rate of elderly patients with a KP BSI episode was 10.7% (27/252), of which CRKP BSI patients (14 / 29, 48.3%) were significantly higher than CSKP patients (13 / 223, 5.83%) (P < 0.001). Hypertension (OR: 13.789, [95% CI: 3.883–48.969], P < 0.001), exposure to carbapenems (OR: 8.073, [95% CI: 2.066–31.537], P = 0.003), and ICU stay (OR: 11.180, [95% CI: 2.663–46.933], P = 0.001) were found to be associated with the development of CRKP BSI in elderly patients. A multivariate analysis showed that isolation of CRKP (OR 2.881, 95% CI 1.228–6.756, P = 0.015) and KP isolated in ICU (OR 11.731, 95% CI 4.226–32.563, P < 0.001) were independent risk factors for 28-day mortality of KP BSI. Conclusion In elderly patients, hypertension, exposure to carbapenems and ICU stay were associated with the development of CRKP BSI. Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection

Mettl3-m6A-Creb1 forms an intrinsic regulatory axis in maintaining iNKT cell pool and functional differentiation

Summary: N6-methyladenosine (m6A) methyltransferase Mettl3 is involved in conventional T cell immunity; however, its role in innate immune cells remains largely unknown. Here, we show that Mettl3 intrinsically regulates invariant natural killer T (iNKT) cell development and function in an m6A-dependent manner. Conditional ablation of Mettl3 in CD4+CD8+ double-positive (DP) thymocytes impairs iNKT cell proliferation, differentiation, and cytokine secretion, which synergistically causes defects in B16F10 melanoma resistance. Transcriptomic and epi-transcriptomic analyses reveal that Mettl3 deficiency disturbs the expression of iNKT cell-related genes with altered m6A modification. Strikingly, Mettl3 modulates the stability of the Creb1 transcript, which in turn controls the protein and phosphorylation levels of Creb1. Furthermore, conditional targeting of Creb1 in DP thymocytes results in similar phenotypes of iNKT cells lacking Mettl3. Importantly, ectopic expression of Creb1 largely rectifies such developmental defects in Mettl3-deficient iNKT cells. These findings reveal that the Mettl3-m6A-Creb1 axis plays critical roles in regulating iNKT cells at the post-transcriptional layer