Pre-training Transformers for Knowledge Graph Completion

Learning transferable representation of knowledge graphs (KGs) is challenging due to the heterogeneous, multi-relational nature of graph structures. Inspired by Transformer-based pretrained language models' success on learning transferable representation for texts, we introduce a novel inductive KG representation model (iHT) for KG completion by large-scale pre-training. iHT consists of a entity encoder (e.g., BERT) and a neighbor-aware relational scoring function both parameterized by Transformers. We first pre-train iHT on a large KG dataset, Wikidata5M. Our approach achieves new state-of-the-art results on matched evaluations, with a relative improvement of more than 25% in mean reciprocal rank over previous SOTA models. When further fine-tuned on smaller KGs with either entity and relational shifts, pre-trained iHT representations are shown to be transferable, significantly improving the performance on FB15K-237 and WN18RR

High-Level PM2.5/PM10 Exposure Is Associated With Alterations in the Human Pharyngeal Microbiota Composition

Previous studies showed that high concentration of particulate matter (PM) 2.5 and PM10 carried a large number of bacterial and archaeal species, including pathogens and opportunistic pathogens. In this study, pharyngeal swabs from 83 subjects working in an open air farmer’s market were sampled before and after exposure to smog with PM2.5 and PM10 levels up to 200 and 300 μg/m3, respectively. Their microbiota were investigated using high-throughput sequencing targeting the V3–V4 regions of the 16S rRNA gene. The genus level phylotypes was increased from 649 to 767 in the post-smog pharyngeal microbiota, of which 142 were new and detected only in the post-smog microbiota. The 142 new genera were traced to sources such as soil, marine, feces, sewage sludge, freshwater, hot springs, and saline lakes. The abundance of the genera Streptococcus, Haemophilus, Moraxella, and Staphylococcus increased in the post-smog pharyngeal microbiota. All six alpha diversity indices and principal component analysis showed that the taxonomic composition of the post-smog pharyngeal microbiota was significantly different to that of the pre-smog pharyngeal microbiota. Redundancy analysis showed that the influences of PM2.5/PM10 exposure and smoking on the taxonomic composition of the pharyngeal microbiota were statistically significant (p < 0.001). Two days of exposure to high concentrations of PM2.5/PM10 changed the pharyngeal microbiota profiles, which may lead to an increase in respiratory diseases. Wearing masks could reduce the effect of high-level PM2.5/PM10 exposure on the pharyngeal microbiota

Summer fast ice evolution off Zhongshan Station, Antarctica

Based on the field data acquired in the program of fast ice observation off Zhongshan Station, Prydz Bay, East Antarctica during the austral summer 2005/2006, physical properties evolution of fast ice during the ice ablation season is analyzed in detail. Results show that the annual maximum ice thickness in 2005 occurred in later November, and then ice started to melt, and the ablation duration was 62 days; sea water under the ice became warmer synchronously; corresponding to the warming sea ice temperature, a "relative cold mid-layer" appeared in sea ice; the fast ice marginal line recoiled back to the shore observably, and the recoil distance was 20.9 km from 18 December 2005 through 14 January 2006. In addition, based on the data of sea ice thickness survey along the investigation course of MV Xuelong on December 18 of 2005, the ice thickness distribution paten in the marginal ice zone have been described: sea ice thickness increased, but the diversity of floe ice thickness decreased from open water to fast ice zone distinctly

Species-Level Analysis of Human Gut Microbiota With Metataxonomics

The current understanding of human gut microbial community is mainly limited to taxonomic features at the genus level. Here, we examined the human gut microbial community at the species level by metataxonomics. To achieve this purpose, a high-throughput approach involving operational phylogenetic unit analysis of the near full-length 16S ribosomal RNA (rRNA) gene sequence was used. A total of 1,235 species-level phylotypes (SLPs) were classified in the feces of 120 Chinese healthy individuals, including 461 previously classified species, 358 potentially new species, and 416 potentially new taxa, which were categorized into low, medium, and high prevalent bacteria groups based on their prevalence. Each individual harbored 186 ± 51 SLPs on average. There was no universal bacterial species shared by all the individuals. However, 90 ± 19 of 116 SLPs were shared in the high prevalent bacteria group. Thirty-two out of thirty-eight species in the high prevalent bacteria group detected in this study were also found in at least one previous study on human gut microbiota based on either culture-dependent or culture-independent approaches. Through compositional analysis, a hierarchical clustering of the prevalence and relative abundance of the 1,235 SLPs revealed two types of gut microbial communities, which were dominated by Prevotella copri and Bacteroides vulgatus, respectively. The type dominated by P. copri was more prevalent in northern China, while the B. vulgatus-dominant type was more prevalent in southern China. Therefore, P- and B-type gut microbial communities in China were proposed. It was found that 166 out of 461 known bacterial species have been previously reported as potential pathogens, and the individuals sampled for this study harbored 20 of these potential pathogenic species on average. The top two most abundant and prevalent potential pathogenic species were Klebsiella pneumoniae and Bacteroides fragilis.This work was supported by grants from the National Science and Technology Major Project of China (2018ZX10712001-007 and 2018ZX10712001-017), the Research Units of Discovery of Unknown Bacteria and Function (2018RU010), the Chinese Academy of Medical Sciences and the Sanming Project of Medicine in Shenzhen (SZSM201811071)

Evidence for distinct mechanisms of small molecule inhibitors of filovirus entry.

Many small molecules have been identified as entry inhibitors of filoviruses. However, a lack of understanding of the mechanism of action for these molecules limits further their development as anti-filoviral agents. Here we provide evidence that toremifene and other small molecule entry inhibitors have at least three distinctive mechanisms of action and lay the groundwork for future development of anti-filoviral agents. The three mechanisms identified here include: (1) direct binding to the internal fusion loop region of Ebola virus glycoprotein (GP); (2) the HR2 domain is likely the main binding site for Marburg virus GP inhibitors and a secondary binding site for some EBOV GP inhibitors; (3) lysosome trapping of GP inhibitors increases drug exposure in the lysosome and further improves the viral inhibition. Importantly, small molecules targeting different domains on GP are synergistic in inhibiting EBOV entry suggesting these two mechanisms of action are distinct. Our findings provide important mechanistic insights into filovirus entry and rational drug design for future antiviral development

Experience with 2 years’ intervention to progressively reduce salt supply to kitchens in elderly care facilities—challenges and further research: post hoc analysis of the DECIDE-Salt randomized clinical trial

Abstract Background Progressive reduction of sodium intake is an attractive approach for addressing excessive salt intake, but evidence for this strategy in real practice is limited. We aimed to determine the feasibility, effectiveness, and safety of a progressive sodium intake reduction intervention in real-world setting. Methods We randomized 48 residential elderly care facilities in China, with 1612 participants aged 55 years and older, to either progressive reduction (PR, 24 facilities) or no reduction (NR, 24 facilities) of the supply of study salt to the kitchens of these facilities for 2 years. The primary efficacy outcome was systolic blood pressure (SBP) at any scheduled follow-up visit. Secondary efficacy outcomes included diastolic blood pressure (DBP) at any scheduled follow-up visit, and major adverse cardiovascular events (comprising non-fatal stroke, non-fatal myocardial infarction, hospitalized non-fatal heart failure, or vascular death) and total mortality. The perception of food saltiness, the addition of out-of-study salt in meals, and 24-h urinary sodium excretion were used as process indicators. Results Pre-specified analysis per randomization found no effect of the intervention on the 2-year overall mean systolic and diastolic blood pressure (SBP, DBP) and any other outcomes. However, post hoc analysis showed that the intervention effect on blood pressure varied over multiple follow-up visits (p for interaction < 0.046) and presented favorable differences at the 24-month visit (SBP =  − 3.0 mmHg, 95%CI =  − 5.6, − 0.5; p = 0.020; DBP =  − 2.0 mmHg, 95%CI − 3.4, − 0.63; p = 0.004). The effect on 24-h sodium was non-significant (− 8.4 mmol, 95%CI =  − 21.8 to 4.9, p = 0.216), though fewer participants with NR than with PR reported food tasting bland (odds ratio 0.46; 95%CI 0.29 to 0.73; p = 0.001). Reporting of bland food taste and other process measures indicated that intervention delivery and adherence were not fully achieved as designed. Conclusions The experience of this real-world study demonstrated that achieving acceptability and sustainability of the progressive sodium intake reduction strategy among older adults was challenging, but it has shown potential for effectiveness in these and potentially other residential settings if the lessons of DECIDE-Salt are applied in further studies. Trial registration ClinicalTrials.gov (NCT03290716)